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The role of prolactin in andrology: what is new?

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Abstract

Prolactin (PRL) has been long deemed as a hormone involved only in female reproduction. However, PRL is a surprising hormone and, since its identification in the 1970s, its attributed functions have greatly increased. However, its specific role in male health is still widely unknown. Recently, low PRL has been associated with reduced ejaculate and seminal vesicle volume in infertile subjects. In addition, in men consulting for sexual dysfunction, hypoprolactinemia has been associated with erectile dysfunction and premature ejaculation, findings further confirmed in the general European population and infertile men. Several metabolic derangements, recapitulating metabolic syndrome, have also been associated with low PRL both in men with sexual dysfunction and from the general European population. In men with sexual dysfunction, followed-up for more than 4 years, low PRL was identified as an independent predictor of the incidence of major adverse cardiovascular events. Finally, an association with anxiety or depressive symptoms has been found in men with sexual dysfunction and from the general European population. While a direct role for impaired PRL function in the pathogenesis of these reproductive, sexual, metabolic and psychological disorders is conceivable, the possibility that low PRL is a mirror of an increased dopaminergic or a decreased serotonergic tone cannot be ruled-out. Hyperactivity of the dopaminergic system can explain only a few of the aforementioned findings, whereas a hypo-serotonergic tone fits well with the clinical features associated with low PRL, and there is significant evidence supporting the hypothesis that PRL could be a mirror of serotonin in the brain.

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References

  1. Burrows HL, Birkmeier TS, Seasholtz AF, Camper SA. Targeted ablation of cells in the pituitary primordia of transgenic mice. Mol Endocrinol. 1996;10:1467–77.

    PubMed  CAS  Google Scholar 

  2. Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW. Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev. 1996;17:639–69.

    PubMed  CAS  Google Scholar 

  3. Nagy E, Berczi I. Hypophysectomized rats depend on residual prolactin for survival. Endocrinology. 1991;128:2776–84.

    Article  PubMed  CAS  Google Scholar 

  4. Kelly PA, Djiane J, Postel-Vinay MC, Edery M. The prolactin/growth hormone receptor family. Endocr Rev. 1991;12:235–51.

    Article  PubMed  CAS  Google Scholar 

  5. Goffin V, Kelly PA. The prolactin/growth hormone receptor family: structure/function relationships. J Mammary Gland Biol Neopl. 1997;2:7–17.

    Article  CAS  Google Scholar 

  6. Goffin V, Ferrag F, Kelly PA. Molecular aspects of prolactin and growth hormone receptors. In: LeRoith D, editor. Advances in molecular and cellular endocrinology, vol. 2. Amsterdam: Elsevier Science; 1998. p. 1–331998.

    Chapter  Google Scholar 

  7. Postel-Vinay MC, Belair L, Kayser C, Kelly PA, Djiane J. Identification of prolactin and growth hormone binding proteins in milk. Proc Natl Acad Sci USA. 1991;188:6687–90.

    Article  Google Scholar 

  8. Fuh G, Wells JA. Prolactin receptor antagonists that inhibit the growth of breast cancer cell lines. J Biol Chem. 1995;270:13133–7.

    Article  PubMed  CAS  Google Scholar 

  9. Amit T, Dibner C, Barkey RJ. Characterization of prolactin and growth hormone-binding proteins in milk and their diversity among species. Mol Cell Endocrinol. 1997;130:167–80.

    Article  PubMed  CAS  Google Scholar 

  10. Goffin V, Shiverick KT, Kelly PA, Martial JA. Sequence function relationships within the expanding family of prolactin, growth hormone, placental lactogen and related proteins in mammals. Endocr Rev. 1996;17:385–410.

    PubMed  CAS  Google Scholar 

  11. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19:225–68.

    Article  PubMed  CAS  Google Scholar 

  12. Feldman M, Ruan W, Cunningham BC, Wells JA, Kleinberg DL. Evidence that the growth hormone receptor mediates differentiation and development of the mammary gland. Endocrinology. 1993;133:1602–8.

    PubMed  CAS  Google Scholar 

  13. Gettler LT, McDade TW, Feranil AB, Kuzawa CW. Prolactin, fatherhood, and reproductive behavior in human males. Am J Phys Anthropol. 2012;148:362–70.

    Article  PubMed  Google Scholar 

  14. Maggi M, Buvat J, Corona G, Guay A, Torres LO. Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA). J Sex Med. 2013;10:661–77.

    Article  PubMed  CAS  Google Scholar 

  15. Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion. Physiol Rev. 2000;80:1523–631.

    PubMed  CAS  Google Scholar 

  16. Matsumoto M, Hidaka K, Tada S, Tasaki Y, Yamaguchi T. Full-length cDNA cloning and distribution of human dopamine D4 receptor. Brain Res Mol Brain Res. 1995;29:157–62.

    Article  PubMed  CAS  Google Scholar 

  17. Valerio A, Alberici A, Tinti C, Spano P, Memo M. Antisense strategy unravels a dopamine receptor distinct from the D2 subtype, uncoupled with adenylyl cyclase, inhibiting prolactin release from rat pituitary cells. J Neurochem. 1994;62:1260–6.

    Article  PubMed  CAS  Google Scholar 

  18. Lledo PM, Legendre P, Israel JM, Vincent JD. Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells. Endocrinology. 1990;127:990–1001.

    Article  PubMed  CAS  Google Scholar 

  19. Elsholtz HP, Lew AM, Albert PR, Sundmark VC. Inhibitory control of prolactin and pit-1 gene promoters by dopamine. Dual signaling pathways required for D2 receptor-regulated expression of the prolactin gene. J Biol Chem. 1991;266:22919–25.

    PubMed  CAS  Google Scholar 

  20. Ishida M, Mitsui T, Yamakawa K, Sugiyama N, Takahashi W, Shimura H, Endo T, Kobayashi T, Arita J. Involvement of cAMP response element-binding protein in the regulation of cell proliferation and the prolactin promoter of lactotrophs in primary culture. Am J Physiol Endocrinol Metab. 2007;293:E1529–37.

    Article  PubMed  CAS  Google Scholar 

  21. Demarest K, Riegle G, Moore K. Prolactin-induced activation of tuberoinfundibular dopaminergic neurons: evidence for both a rapid “tonic” and a delayed “induction” component. Neuroendocrinology. 1984;38:467–75.

    Article  PubMed  CAS  Google Scholar 

  22. Gudelsky GA, Porter JC. Release of dopamine from tuberoinfundibular neurons into pituitary stalk blood after prolactin or haloperidol administration. Endocrinology. 1980;106:526–9.

    Article  PubMed  CAS  Google Scholar 

  23. Demarest KT, McKay DW, Riegle GD, Moore KE. Sexual differences in tuberoinfundibular dopamine nerve activity induced by neonatal androgen exposure. Neuroendocrinology. 1981;32:108–13.

    Article  PubMed  CAS  Google Scholar 

  24. Kamberi IA, Mical RS, Porter JC. Effects of melatonin and serotonin on the release of FSH and prolactin. Endocrinology. 1971;88:1288–93.

    Article  PubMed  CAS  Google Scholar 

  25. Clemens JA, Sawyer BD, Cerimele B. Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion. Endocrinology. 1977;100:692–8.

    Article  PubMed  CAS  Google Scholar 

  26. Kato Y, Nakai Y, Imura H, Chihara K, Ogo S. Effect of 5-hydroxytryptophan (5-HTP) on plasma prolactin levels in man. J Clin Endocrinol Metab. 1974;38:695–7.

    Article  PubMed  CAS  Google Scholar 

  27. Chen HJ, Meites J. Effects of biogenic amines and TRH on release of prolactin and TSH in the rat. Endocrinology. 1975;96:10–4.

    Article  PubMed  CAS  Google Scholar 

  28. Kordon C, Blake CA, Terkel J, Sawyer CH. Participation of serotonin-containing neurons in the suckling-induced rise in plasma prolactin levels in lactating rats. Neuroendocrinology. 1973-1974;13:213–23.

  29. Gallo RV, Rabii J, Moberg GP. Effect of methysergide, a blocker of serotonin receptors, on plasma prolactin levels in lactating and ovariectomized rats. Endocrinology. 1975;97:1096–105.

    Article  PubMed  CAS  Google Scholar 

  30. Lawson DM, Gala RR. The influence of pharmacological manipulation of serotonergic and dopaminergic mechanisms on plasma prolactin in ovariectomized, estrogen-treated rats. Endocrinology. 1978;102:973–81.

    Article  PubMed  CAS  Google Scholar 

  31. Fessler RG, Deyo SN, Meltzer HY, Miller RJ. Evidence that the medial and dorsal raphe nuclei mediate serotonergically-induced increases in prolactin release from the pituitary. Brain Res. 1984;299:231–7.

    Article  PubMed  CAS  Google Scholar 

  32. Van de Kar LD, Bethea CL. Pharmacological evidence that serotonergic stimulation of prolactin secretion is mediated via the dorsal raphe nucleus. Neuroendocrinology. 1982;35:225–30.

    Article  PubMed  Google Scholar 

  33. Calogero AE, Bagdy G, Burrello N, Polosa P, D’Agata R. Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures. Eur J Endocrinol. 1995;133:251–4.

    Article  PubMed  CAS  Google Scholar 

  34. Calogero AE, Bagdy G, Moncada ML, D’Agata R. Effect of selective serotonin agonists on basal, corticotrophin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary cells. J Endocrinol. 1993;136:381–7.

    Article  PubMed  CAS  Google Scholar 

  35. Lamberts SW, MacLeod RM. The interaction of the serotonergic and dopaminergic systems on prolactin secretion in the rat. The mechanism of action of the “specific” serotonin receptor antagonist, methysergide. Endocrinology. 1978;103:287–95.

    Article  PubMed  CAS  Google Scholar 

  36. Lamberts SW, MacLeod RM. Metergoline and other peripheral serotonin antagonists inhibit prolactin secretion through mechanisms unrelated to serotonin. Proc Soc Exp Biol Med. 1979;162:75–9.

    Article  PubMed  CAS  Google Scholar 

  37. Delitala G, Yeo T, Stubbs WA, Jones A. Besser GM. In: Cattibeni G, Racagni G, Spano PF, Costa E, editors. Long term effects of neuroleptics. New York: Raven; 1979. p. 443–4.

    Google Scholar 

  38. Bagdy G, Makara GB. Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin, and corticosterone responses. Endocrinology. 1994;134:1127–31.

    PubMed  CAS  Google Scholar 

  39. Bagdy G, Makara GB. Paraventricular nucleus controls 5-HT2C receptor-mediated corticosterone and prolactin but not oxytocin and penile erection responses. Eur J Pharmacol. 1995;275:301–5.

    Article  PubMed  CAS  Google Scholar 

  40. Hair WM, Gubbay O, Jabbour HN, Lincoln GA. Prolactin receptor expression in human testis and accessory tissues: localization and function. Mol Hum Reprod. 2002;8:606–11.

    Article  PubMed  CAS  Google Scholar 

  41. Jabbour HN, Lincoln GA. Prolactin receptor expression in the testis of the ram: localisation, functional activation and the influence of gonadotrophins. Mol Cell Endocrinol. 1999;148:151–61.

    Article  PubMed  CAS  Google Scholar 

  42. Ishida M, Yoshida M, Fukuta S, Uemura K, Iijima M, Horiguchi K, Harigaya T. Analysis of prolactin gene expression and cleaved prolactin variants in the mouse testis and spermatozoa. J Reprod Dev. 2010;56:567–74.

    Article  PubMed  CAS  Google Scholar 

  43. Takase M, Tsutsui K, Kawashima S. Effects of prolactin and bromocryptine on the regulation of testicular luteinizing hormone receptors in mice. J Exp Zool. 1990;256:200–9.

    Article  PubMed  CAS  Google Scholar 

  44. Dombrowicz D, Sente B, Closset J, Hennen G. Dose-dependent effects of human prolactin on the immature hypophysectomized rat testis. Endocrinology. 1992;130:695–700.

    PubMed  CAS  Google Scholar 

  45. Chandrashekar V, Bartke A. Influence of endogenous prolactin on the luteinizing hormone stimulation of testicular steroidogenesis and the role of prolactin in adult male rats. Steroids. 1988;51:559–76.

    Article  PubMed  CAS  Google Scholar 

  46. Rubin RT, Poland RE, Tower BB. Prolactin-related testosterone secretion in normal adult men. J Clin Endocrinol Metab. 1976;42:112–6.

    Article  PubMed  CAS  Google Scholar 

  47. Takeyama M, Nagareda T, Takatsuka D, Namiki M, Koizumi K, Aono T, Matsumoto K. Stimulatory effect of prolactin on luteinizing hormone-induced testicular 5 alpha-reductase activity in hypophysectomized adult rats. Endocrinology. 1986;118:2268–75.

    Article  PubMed  CAS  Google Scholar 

  48. Gunasekar PG, Kumaran B, Govindarajulu P. Prolactin and leydig cell steroidogenic enzymes in the bonnet monkey (macaca radiata). Int J Androl. 1988;11:53–9.

    Article  PubMed  CAS  Google Scholar 

  49. Gunasekar PG, Kumaran B, Govindarajulu P. Role of prolactin on leydig, sertoli and germ cellular neutral lipids in bonnet monkeys, macaca radiata. Endocrinologia Japonica. 1991;38:1–8.

    Article  PubMed  CAS  Google Scholar 

  50. Grosdemouge I, Bachelot A, Lucas A, Baran N, Kelly PA, Binart N. Effects of deletion of the prolactin receptor on ovarian gene expression. Reprod Biol Endocrinol. 2003;1:12–27.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Binart N, Melaine N, Pineau C, Kercret H, Touzalin AM, Imbert-Bolloré P, Kelly PA, Jégou B. Male reproductive function is not affected in prolactin receptor-deficient mice. Endocrinology. 2003;144:3779–82.

    Article  PubMed  CAS  Google Scholar 

  52. Robertson FG, Harris J, Naylor MJ, Oakes SR, Kindblom J, Dillner K, Wennbo H, Törnell J, Kelly PA, Green J, Ormandy CJ. Prostate development and carcinogenesis in prolactin receptor knockout mice. Endocrinology. 2003;144:3196–205.

    Article  PubMed  CAS  Google Scholar 

  53. Ormandy CJ, Camus A, Barra J, Damotte D, Lucas B, Buteau H, Edery M, Brousse N, Babinet C, Binart N, Kelly PA. Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev. 1997;11:167–78.

    Article  PubMed  CAS  Google Scholar 

  54. Steger RW, Chandrashekar V, Zhao W, Bartke A, Horseman ND. Neuroendocrine and reproductive functions in male mice with targeted disruption of the prolactin gene. Endocrinology. 1998;139:3691–5.

    PubMed  CAS  Google Scholar 

  55. Lincoln GA, Clarke IJ, Sweeney T. ‘Hamster-like’ cycles in testicular size in the absence of gonadotrophin secretion in HPD rams exposed to long-term changes in photoperiod and treatment with melatonin. J Neuroendocrinol. 1996;8:855–66.

    Article  PubMed  CAS  Google Scholar 

  56. Newey PJ, Gorvin CM, Cleland SJ, Willberg CB, Bridge M, Azharuddin M, Drummond RS, van der Merwe PA, Klenerman P, Bountra C, Thakker RV. Mutant prolactin receptor and familial hyperprolactinemia. N Engl J Med. 2013;369:2012–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Huhtaniemi I, Parvinen M, Venho P, Rannikko S. Combination of a GnRH agonist with an antiandrogen or bromocriptine in the treatment of prostatic cancer; slight potentiation of antigonadal effects. Int J Androl. 1991;14:374–86.

    Article  PubMed  CAS  Google Scholar 

  58. Ufearo CS, Orisakwe OE. Restoration of normal sperm characteristics in hypoprolactineamic infertile men treated with metaclopromide and exogenous prolactin. Clin. Pharmacol. Therapeut. 1995;58:354–9.

    Article  CAS  Google Scholar 

  59. Pujianto DA, Curry BJ, Aitken RJ. Prolactin exerts a prosurvival effect on human spermatozoa via mechanisms that involve the stimulation of Akt phosphorylation and suppression of caspase activation and capacitation. Endocrinology. 2010;151:1269–79.

    Article  PubMed  CAS  Google Scholar 

  60. Lotti F, Corona G, Maseroli E, Rossi M, Silverii A, Degl’innocenti S, Rastrelli G, Forti G, Maggi M. Clinical implications of measuring prolactin levels in males of infertile couples. Andrology. 2013;1:764–71.

    Article  PubMed  CAS  Google Scholar 

  61. Negro-Vilar A, Saad WA, McCann SM. Evidence for a role of prolactin in prostate and seminal vesicle growth in immature male rats. Endocrinology. 1977;100:729–37.

    Article  PubMed  CAS  Google Scholar 

  62. Bartke A, Smith MS, Michael SD, Peron FG, Dalterio S. Effects of experimentally-induced chronic hyperprolactinemia on testosterone and gonadotropin levels in male rats and mice. Endocrinology. 1977;100:182–6.

    Article  PubMed  CAS  Google Scholar 

  63. Bartke A Effects of inhibitors of pituitary prolactin release on testicular cholesterol stores, seminal vesicles weight, fertility, and lactation in mice. Biol Reprod. 1974;11:319–25.

    Article  PubMed  CAS  Google Scholar 

  64. Nevalainen MT, Valve EM, Ahonen T, Yagi A, Paranko J, Härkönen PL. Androgen-dependent expression of prolactin in rat prostate epithelium in vivo and in organ culture. FASEB J. 1997;11:1297–307.

    PubMed  CAS  Google Scholar 

  65. Wennbo H, Kindblom J, Isaksson OG, Tornell J. Transgenic mice overexpressing the prolactin gene develop dramatic enlargement of the prostate gland. Endocrinology. 1997;138:4410–5.

    PubMed  CAS  Google Scholar 

  66. Ravault JP, Courot M, Garnier D, Pelletier J, Terqui M. Effect of 2-bromo-α-ergocryptine (CB154) on plasma prolactin, LH and testosterone levels, accessory reproductive glands and spermatogenesis in lambs during puberty. Biol Reprod. 1977;17:192–7.

    Article  PubMed  CAS  Google Scholar 

  67. Arunakaran J, Balasubramanian K, Srinivasan N, Aruldhas MM, Govindarajulu P. Effects of androgens, prolactin and bromocryptine on seminal vesicular enzymes of the pyruvate malate cycle involved in lipogenesis in castrated mature monkeys, macaca radiata. Int J Androl. 1988;11:133–9.

    Article  PubMed  CAS  Google Scholar 

  68. Nicoll C Ontogeny and evolution of prolactins' function. Fed Proc. 1980;39:2563–6.

    PubMed  CAS  Google Scholar 

  69. Nevalainen MT, Valve EM, Ingleton PM, Nurmi M, Martikainen PM, Harkonen PL. Prolactin and prolactin receptors are expressed and functioning in human prostate. J Clin Invest. 1997b;99:618–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Jacobson EM, Hugo ER, Borcherding DC, Ben-Jonathan N. Prolactin in breast and prostate cancer: molecular and genetic perspectives. Discov Med. 2011;11:315–24.

    PubMed  Google Scholar 

  71. Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, Maggi M. Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction. J Sex Med. 2009;6:1457–66.

    Article  PubMed  CAS  Google Scholar 

  72. Corona G, Wu FC, Rastrelli G, Lee DM, Forti G, O’Connor DB, O’Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Huhtaniemi IT, Kula K, Punab M, Vanderschueren D, Rutter MK, Maggi M, EMAS Study Group. Low prolactin is associated with sexual dysfunction and psychological or metabolic disturbances in middle-aged and elderly men: the European male aging study (EMAS). J Sex Med. 2014;11:240–53.

    Article  PubMed  CAS  Google Scholar 

  73. Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol. 2012;9:508–19.

    Article  PubMed  CAS  Google Scholar 

  74. Corona G, Jannini EA, Lotti F, Boddi V, De Vita G, Forti G, Lenzi A, Mannucci E, Maggi M. Premature and delayed ejaculation: two ends of a single continuum influenced by hormonal milieu. Int J Androl. 2011;34:41–8.

    Article  PubMed  CAS  Google Scholar 

  75. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA. Wass JA; endocrine society. Diagnosis and treatment of hyperprolactinemia: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2011;96:273–88.

    CAS  Google Scholar 

  76. Buvat J Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15:373–7.

    Article  PubMed  CAS  Google Scholar 

  77. Ciccarelli A, Guerra E, De Rosa M, Milone F, Zarrilli S, Lombardi G, Colao A. PRL secreting adenomas in male patients. Pituitary. 2005;8:39–42.

    Article  PubMed  Google Scholar 

  78. Corona G, Mannucci E, Fisher AD, Lotti F, Ricca V, Balercia G, Petrone L, Forti G, Maggi M. Effect of hyperprolactinemia in male patients consulting for sexual dysfunction. J Sex Med. 2007;4:1485–93.

    Article  PubMed  CAS  Google Scholar 

  79. Corona G, Rastrelli G, Ricca V, Jannini EA, Vignozzi L, Monami M, Sforza A, Forti G, Mannucci E, Maggi M. Risk factors associated with primary and secondary reduced libido in male patients with sexual dysfunction. J Sex Med. 2013;10:1074–89.

    Article  PubMed  Google Scholar 

  80. Nair S, Milsom S. Anejaculation as the presenting feature of pituitary microadenoma. Fertil Steril. 2012;2008(90):e21–3.

    Google Scholar 

  81. Ishikawa H, Kaneko S, Ohashi M, Nakagawa K, Hata M. Retrograde ejaculation accompanying hyperprolactinemia. Arch Androl. 1993;30:153–5.

    Article  PubMed  CAS  Google Scholar 

  82. Corona G, Mannucci E, Petrone L, Fisher AD, Balercia G, de Scisciolo G, Pizzocaro A, Giommi R, Chiarini V, Forti G, Maggi M. Psychobiological correlates of delayed ejaculation in male patients with sexual dysfunctions. J Androl. 2006;27:453–8.

    Article  PubMed  Google Scholar 

  83. Rastrelli G, Carter EL, Ahern T, Finn JD, Antonio L, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Keevil B, Maggi M, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Vanderschueren D, Wu FC, EMAS Study Group. Development of and recovery from secondary hypogonadism in aging men: prospective results from the EMAS. J Clin Endocrinol Metab. 2015;100:3172–82.

    Article  PubMed  CAS  Google Scholar 

  84. Carter JN, Tyson JE, Tolis G, Van Vliet S, Faiman C, Friesen HG. Prolactin-screening tumours and hypogonadism in 22 men. N Engl J Med. 1978;299:847–52.

    Article  PubMed  CAS  Google Scholar 

  85. Prescott RW, Johnston DG, Kendall-Taylor P, Crombie A, Hall K, McGregor A, Hall R. Hyperprolactinemia in men-response to bromocriptine therapy. Lancet. 1982;1:245–8.

    Article  PubMed  CAS  Google Scholar 

  86. Buvat J, Maggi M, Gooren L, Guay AT, Kaufman J, Morgentaler A, Schulman C, Tan HM, Torres LO, Yassin A, Zitzmann M. Endocrine aspects of male sexual dysfunctions. J Sex Med. 2010;7:1627–56.

    Article  PubMed  Google Scholar 

  87. Cruz-Casallas PE, Nasello AG, Hucke EE, Felicio LF. Dual modulation of male sexual behavior in rats by central prolactin: relationship with in vivo striatal dopaminergic activity. Psychoneuroendocrinology. 1999;24:681–93.

    Article  PubMed  CAS  Google Scholar 

  88. Seo Y, Jeong B, Kim JW, Choi J. Plasma concentration of prolactin, testosterone might be associated with brain response to visual erotic stimuli in healthy heterosexual males. Psychiatry Investig. 2009;6:194–203.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Redouté J, Stoléru S, Grégoire MC, Costes N, Cinotti L, Lavenne F, Le Bars D, Forest MG, Pujol JF. Brain processing of visual sexual stimuli in human males. Hum Brain Mapp. 2000;11:162–77.

    Article  PubMed  Google Scholar 

  90. Paglietti E, Peliegrini-Quarantotti B, Mereu G, Gessa GL. Apomorphine and L-DOPA lower ejaculation threshold in the male rat. Physiol Behav. 1978;20:559–62.

    Article  PubMed  CAS  Google Scholar 

  91. Tagliamonte A, Fratta W, Del Fiacco M, Gessa GL. Possible stimulatory role of brain dopamine in the copulatory behavior of male rats. Pharmacol Biochem Behav. 1974;2:257–60.

    Article  PubMed  CAS  Google Scholar 

  92. Tagliamonte A, Fratta W, Gessa GL. Aphrodisiac effect of L-DOPA and apomorphine in male sexually sluggish rats. Experientia. 1974;30:381–2.

    Article  PubMed  CAS  Google Scholar 

  93. Malmnas CO. The significance of dopamine vs. other catecholamines for L-DOPA-induced facilitation of sexual behavior in the castrated male rat. Pharmacol Biochem Behav. 1976;4:521–6.

    Article  PubMed  CAS  Google Scholar 

  94. Malmnas CO. Dopaminergic reversal of the decline after castration of rat copulatory behaviour. J Endocr. 1977;73:187–8.

    Article  PubMed  CAS  Google Scholar 

  95. Napoli-Farris L, Fratta W, Gessa GL. Stimulation of dopamine autoreceptors elicits "premature ejaculation" in rats. Pharmacol Biochem Behav. 1984;20:69–72.

    Article  PubMed  CAS  Google Scholar 

  96. Pfaus JG, Phillips AA. Differential effects of dopamine receptor antagonists on the sexual behavior of male rats. Psychopharmacology. 1989;98:363–8.

    Article  PubMed  CAS  Google Scholar 

  97. Pfaus JG, Phillips AG. Role of dopamine in anticipatory and consummatory aspects of sexual behavior in the male rat: I. Effects of systemic administration of dopamine antagonists. Behav Neurosci. 1991;105:727–43.

    Article  PubMed  CAS  Google Scholar 

  98. Argiolas A, Melis MR. Neuromodulation of penile erection: an overview of the role of neurotransmitters and neuropeptides. Prog Neurobiol. 1995;47:235–55.

    Article  PubMed  CAS  Google Scholar 

  99. Lindell SG, Suomi SJ, Shoaf S, Linnoila M, Higley JD. Salivary prolactin as a marker for central serotonin turnover. Biol Psychiatry. 1999;46:568–72.

    Article  PubMed  CAS  Google Scholar 

  100. Flory JD, Manuck SB, Perel JM, Muldoon MF. A comparison of d, l-fenfluramine and citalopram challenges in healthy adults. Psychopharmacology. 2004;174:376–80.

    Article  PubMed  CAS  Google Scholar 

  101. Murphy DL, Mellow AM, Sunderland T, Aulakh CS, Lawlor BL, Zohar J. Strategies for the study of serotonin in humans. In: Coccaro EF, Murphy DL editors. Serotonin in major psychiatric disorders. Washington D.C.: American Psychiatric Press; 1990. pp 2–25

  102. Yatham LN, Steiner M. Neuroendocrine probes of serotonergic function: a critical review. Life Sci. 1993;53:447–63.

    Article  PubMed  CAS  Google Scholar 

  103. Seifritz E, Baumann P, Muller MJ, Annen O, Amey M, Hemmeter U, Hatzinger M, Chardon F, Holsboer-Trachsler E. Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. Neuropsychopharmacology. 1996;14:253–63.

    Article  PubMed  CAS  Google Scholar 

  104. Attenburrow MJ, Mitter PR, Whale R, Terao T, Cowen PJ. Low-dose citalopram as a 5-HT neuroendocrine probe. Psychopharmacology. 2001;155:323–6.

    Article  PubMed  CAS  Google Scholar 

  105. Lotrich FE, Bies R, Muldoon MF, Manuck SB, Smith GS, Pollock BG. Neuroendocrine response to intravenous citalopram in healthy control subjects: pharmacokinetic influences. Psychopharmacology. 2005;178:268–75.

    Article  PubMed  CAS  Google Scholar 

  106. Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, Wikström H, Sanchez D, Arvidsson LE, Hacksell U, Nilsson JL. Effects of a new type of 5-HT receptor agonist on male rat sexual behaviour. Pharmacol Biochem Behav. 1981;15:785–92.

    Article  PubMed  CAS  Google Scholar 

  107. Foreman MM, Hall JL, Love RL. The role of the 5-HT2 receptor in the regulation of sexual performance of male rats. Life Sci. 1989;45:1263–70.

    Article  PubMed  CAS  Google Scholar 

  108. Waldinger MD. The neurobiological approach to premature ejaculation. J Urol. 2002;168:2359–67.

    Article  PubMed  Google Scholar 

  109. Waldinger MD, Zwinderman AH, Olivier B. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone. J Clin Psychopharmacol. 2001;21:293–7.

    Article  PubMed  CAS  Google Scholar 

  110. Waldinger MD, Zwinderman AH, Olivier B. Antidepressants and ejaculation: a double-blind, randomized, fixed-dose study with mirtazapine and paroxetine. J Clin Psychopharmacol. 2003;23:467–70.

    Article  PubMed  CAS  Google Scholar 

  111. Baraldi M, Benassi-Benelli A, Lolli M. Penile erections in rats after fenfluramine admimstration. Rio Farmacoi Ter. 1977;8:375–9.

    CAS  Google Scholar 

  112. Szele FG, Murphy DL, Garrick NA. Effects of fenfluramine, m-chlorophenylpiperazine. And other serotonin related agonists and antagonists on penile erection in nonhuman primates. Life Sci. 1988;43:1297–304.

    Article  PubMed  CAS  Google Scholar 

  113. Berendsen HHG, Broekkamp CLE. Drug-induced penile erection in rats: indications of serotoninla receptor mediation. Eur J Pharmac. 1987;135:279–87.

    Article  CAS  Google Scholar 

  114. Berendsen HHG, Jenck F, Broekkamp CLE. Involvement of 5-HT,c-receptors in drug-induced penile erections in rats. Psychopharmacology. 1990;101:57–61.

    Article  PubMed  CAS  Google Scholar 

  115. Pomerantz SM, Hepner BC, Wertz M. Serotoninergic mfluences on male sexual behavior of rhesus monkeys: Effect of serotonin agonists. Psychophnrmaco1ogy 1993;111:47–54

  116. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome–a new world-wide definition. A consensus statement from the international diabetes federation. Diabet Med. 2006;23:469–80.

    Article  PubMed  CAS  Google Scholar 

  117. Wang T, Lu J, Xu Y, Li M, Sun J, Zhang J, Xu B, Xu M, Chen Y, Bi Y, Wang W, Ning G. Circulating prolactin associates with diabetes and impaired glucose regulation: a population-based study. Diabetes Care. 2013;36:1974–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Chirico V, Cannavò S, Lacquaniti A, Salpietro V, Mandolfino M, Romeo PD, Cotta O, Munafò C, Giorgianni G, Salpietro C, Arrigo T. Prolactin in obese children: a bridge between inflammation and metabolic-endocrine dysfunction. Clin Endocrinol. 2013;79:537–44.

    Article  CAS  Google Scholar 

  119. Corona G, Rastrelli G, Boddi V, Monami M, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M. Prolactin levels independently predict major cardiovascular events in patients with erectile dysfunction. Int J Androl. 2011;34:217–24.

    Article  PubMed  CAS  Google Scholar 

  120. Corona G, Monami M, Boddi V, Cameron-Smith M, Lotti F, de Vita G, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M. Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction. J Sex Med. 2010;7:1918–27.

    Article  PubMed  Google Scholar 

  121. Rastrelli G, Corona G, Fisher AD, Silverii A, Mannucci E, Maggi M. Two unconventional risk factors for major adverse cardiovascular events in subjects with sexual dysfunction: low education and reported partner’s hypoactive sexual desire in comparison with conventional risk factors. J Sex Med. 2012;9:3227–38.

    Article  PubMed  Google Scholar 

  122. Rastrelli G, Corona G, Lotti F, Aversa A, Bartolini M, Mancini M, Mannucci E, Maggi M. Flaccid penile acceleration as a marker of cardiovascular risk in men without classical risk factors. J Sex Med. 2014;11:173–86.

    Article  PubMed  Google Scholar 

  123. Haring R, Völzke H, Vasan RS, Felix SB, Nauck M, Dörr M, Wallaschofski H. Sex-specific associations of serum prolactin concentrations with cardiac remodeling: longitudinal results from the study of health Pomerania (SHIP). Atherosclerosis. 2012;221:570–6.

    Article  PubMed  CAS  Google Scholar 

  124. Smith SR. The endocrinology of obesity. Endocrinol Metab Clin N Am. 1996;25:921–42.

    Article  CAS  Google Scholar 

  125. Weaver JU, Noonan K, Kopelman PG. An association between hypothalamic-pituitary dysfunction and peripheral endocrine function in extreme obesity. Clin Endocrinol (Oxford). 1991;35:97–102.

    Article  CAS  Google Scholar 

  126. Donders SH, Pieters GF, Heevel JG, Ross HA, Smals AG, Kloppenborg PW. Disparity of thyrotropin (TSH) and prolactin responses to TSH-releasing hormone in obesity. J Clin Endocrinol Metab. 1985;61:56–9.

    Article  PubMed  CAS  Google Scholar 

  127. Lala VR, Ray A, Jamias P, Te D, Orteza N, Fiscina B, Noto R. Prolactin and thyroid status in prepubertal children with mild to moderate obesity. J Am Coll Nutr. 1988;7:361–6.

    Article  PubMed  CAS  Google Scholar 

  128. Röjdmark S, Rössner S. Decreased dopaminergic control of prolactin secretion in male obesity: normalization by fasting. Metabolism. 1991;40:191–5.

    Article  PubMed  Google Scholar 

  129. Copinschi G, De Laet MH, Brion JP, Leclercq R, L’Hermite M, Robyn C, Virasoro E, Van Cauter E. Simultaneous study of cortisol, growth hormone and prolactin nyctohemeral variations in normal and obese subjects. Influence of prolonged fasting in obesity. Clin Endocrinol. 1978;9:15–26.

    Article  CAS  Google Scholar 

  130. Kopelman PG. Physiopathology of prolactin secretion in obesity. Int J Obes Relat Metab Disord. 2000;24(Suppl 2):S104–8.

    Article  PubMed  CAS  Google Scholar 

  131. Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in Humans? Endocr Rev. 2008;29:1–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Strader AD, Buntin JD. Changes in agouti-related peptide during the ring dove breeding cycle in relation to prolactin and parental hyperphagia. J Neuroendocrinol. 2003;15:1046–53.

    Article  PubMed  CAS  Google Scholar 

  133. Silverin B, Goldsmith AR. Plasma prolactin concentrations in breeding pied flycatchers (ficedula hypoleuca) with an experimentally prolonged brooding period. Horm Behav. 1990;24:104–13.

    Article  PubMed  CAS  Google Scholar 

  134. Pérez-Villamil B, Bordiú E, Puente-Cueva M. Involvement of physiological prolactin levels in growth and prolactin receptor content of prostate glands and testes in developing male rats. J Endocrinol. 1992;132:449–59.

    Article  PubMed  Google Scholar 

  135. Lemini M, Ruiz-Herrera X, Ledesma-Colunga MG, Díaz-Lezama N, De Los Ríos EA, López-Barrera F, Méndez I. Martínez de la escalera G, macotela Y, Clapp C. Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-β and TNF-α. Am J Physiol Regul Integr Comp Physiol. 2015;308:R792–9.

    Article  PubMed  CAS  Google Scholar 

  136. Sondermeijer BM, Klein Twennaar CF, Kastelein JJ, Franssen EJ, Hutten BA, Dallinga-Thie GM, Stroes ES, Fliers E, Twickler MT, Serlie MJ. Infusion of a lipid emulsion in healthy men decreases the serotonergic response. Neuroendocrinology. 2012;95:325–31.

    Article  PubMed  CAS  Google Scholar 

  137. Arumugam R, Horowitz E, Noland RC, Lu D, Fleenor D, Freemark M. Regulation of islet beta-cell pyruvate metabolism: interactions of prolactin, glucose, and dexamethasone. Endocrinology. 2010;15:3074–83.

    Article  CAS  Google Scholar 

  138. Yamamoto T, Mita A, Ricordi C, Messinger S, Miki A, Sakuma Y, Timoneri F, Barker S, Fornoni A, Molano RD, Inverardi L, Pileggi A, Ichii H. Prolactin supplementation to culture medium improves beta-cell survival. Transplantation. 2010;89:1328–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Brandebourg TD, Bown JL, Ben JN. Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue. Biochem Biophys Res Commun. 2007;357:408–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Freemark M, Avril I, Fleenor D, Driscoll P, Petro A, Opara E, Kendall W, Oden J, Bridges S, Binart N, Breant B, Kelly PA. Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance. Endocrinology. 2002;143:1378–85.

    Article  PubMed  CAS  Google Scholar 

  141. Flint DJ, Clegg RA, Vernon RG. Prolactin and the regulation of adipose-tissue metabolism during lactation in rats. Mol Cel Endocrinol. 1981;22:265–75.

    Article  CAS  Google Scholar 

  142. de Moura EG, Bonomo IT, Nogueira-Neto JF, de Oliveira E, Trevenzoli IH, Reis AM, Passos MC. Lisboa PC maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny. J Physiol. 2009;587:4919–29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Kopelman PG, Pilkington TR, Jeffcoate SL, White N. Persistence of defective hypothalamic control of prolactin secretion in some obese women after weight reduction. Br Med J. 1980;281:358–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Kopelman PG, White N, Pilkington TR, Jeffcoate SL. Impaired hypothalamic control of prolactin secretion in massive obesity. Lancet. 1979;1:747–50.

    Article  PubMed  CAS  Google Scholar 

  145. Plewe G, Schneider U, Krause U, Beyer J. Naloxone increases the response of growth hormone and prolactin to stimuli in obese humans. J Endocrinol Investig. 1987;10:137–41.

    Article  CAS  Google Scholar 

  146. Ling C, Svensson L, Odén B, Weijdegård B, Edén B, Edén S, Billig H. Identification of functional prolactin (PRL) receptor gene expression: PRL inhibits lipoprotein lipase activity in human white adipose tissue. J Clin Endocrinol Metab. 2003;88:1804–8.

    Article  PubMed  CAS  Google Scholar 

  147. Hogan JC, Stephens JM. The regulation of fatty acid synthase by STAT5A. Diabetes. 2005;54:1968–75.

    Article  PubMed  CAS  Google Scholar 

  148. Nilsson L, Binart N, Bohlooly YM, Bramnert M, Egecioglu E, Kindblom J, Kelly PA, Kopchick JJ, Ormandy CJ, Ling C, Billig H. Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun. 2005;331:1120–6.

    Article  PubMed  CAS  Google Scholar 

  149. Hugo ER, Brandebourg TD, Comstock CE, Gersin KS, Sussman JJ, Ben-Jonathan N. LS14: a novel human adipocyte cell line that produces prolactin. Endocrinology. 2006;147:306–13.

    Article  PubMed  CAS  Google Scholar 

  150. Doknic M, Pekic S, Zarkovic M, Medic-Stojanoska M, Dieguez C, Casanueva F, Popovic V. Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine. Eur J Endocrinol. 2002;147:77–84.

    Article  PubMed  CAS  Google Scholar 

  151. Berinder K, Nyström T, Höybye C, Hall K, Hulting AL. Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary. 2011;14:199–207.

    Article  PubMed  CAS  Google Scholar 

  152. Galluzzi F, Salti R, Stagi S, La Cauza F, Chiarelli F. Reversible weight gain and prolactin levelsdlong-term follow-up in childhood. J Pediatr Endocrinol Metab. 2005;18:921–4.

    Article  PubMed  CAS  Google Scholar 

  153. Park S, Kim S, Daily JW, Kim SH. Serum prolactin concentrations determine whether they improve or impair b-cell function and insulin sensitivity in diabetic rats. Diabetes Metab Res Rev. 2011;27:564–74.

    Article  PubMed  CAS  Google Scholar 

  154. Park S, Kang S, Lee HW, Ko BS. Central prolactin modulates insulin sensitivity and insulin secretion in diabetic rats. Neuroendocrinology. 2012;95:332–43.

    Article  PubMed  CAS  Google Scholar 

  155. Lyons DJ, Hellysaz A, Broberger C. Prolactin regulates tuberoinfundibular dopamine neuron discharge pattern: novel feedback control mechanisms in the lactotrophic axis. J Neurosci. 2012;32:8074–83.

    Article  PubMed  CAS  Google Scholar 

  156. Vigas M, Klimes I, Jurcovicová J, Jezová D. Acute elevation of endogenous prolactin does not influence glucose homeostasis in healthy men. Physiol Res. 1993;42:341–5.

    PubMed  CAS  Google Scholar 

  157. Katz EJ, Donald RA, Beaven DW, Espiner EA. Lack of effect of hyperprolactinemia on glucose disposal and insulin secretion in patients with prolactinomas. Horm Metab Res. 1991;13:667–9.

    Article  Google Scholar 

  158. Baik JH. Dopamine signaling in food addiction: role of dopamine D2 receptors. BMB Rep. 2013;46:519–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Stice E, Yokum S, Zald D, Dagher A. Dopamine-based reward circuitry responsivity, genetics, and overeating. Curr Top Behav Neurosci. 2011;6:81–93.

    Article  PubMed  Google Scholar 

  160. Salamone JD, Correa M. Dopamine and food addiction: lexicon badly needed. Biol Psychiatry. 2013;73:e15–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Wang GJ, Volkow ND, Thanos PK, Fowler JS. Imaging of brain dopamine pathways: implications for understanding obesity. J Addict Med. 2009;3:8–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F. Imaging dopamine’s role in drug abuse and addiction. Neuropharmacology. 2009;56:3–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Ritchie T, Noble EP. Association of seven polymorphisms of the D2 dopamine receptor gene with brain receptor-binding characteristics. Neurochem Res. 2003;28:73–82.

    Article  PubMed  CAS  Google Scholar 

  164. Epstein LH, Wright SM, Paluch RA, Leddy JJ, Hawk LW, Jaroni JL, Saad FG, Crystal-Mansour S, Shields PG, Lerman C Relation between food reinforcement and dopamine genotypes and its effect on food intake in smokers. Am J Clin Nutr. 2004;80:82–8.

    PubMed  CAS  Google Scholar 

  165. Epstein LH, Temple JL, Neaderhiser BJ, Salis RJ, Erbe RW, Leddy JJ. Food reinforcement, the dopamine D2 receptor genotype, and energy intake in obese and nonobese humans. Behav Neurosci. 2007;121:877–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Barnard ND, Noble EP, Ritchie T, Cohen J, Jenkins DJ, Turner-McGrievy G, Gloede L, Green AA, Ferdowsian H. D2 dopamine receptor Taq1A polymorphism, body weight, and dietary intake in type 2 diabetes. Nutrition. 2009;25:58–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Luo S, Liang Y, Cincotta AH. Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters. Neuroendocrinology. 1999;69:160–6.

    Article  PubMed  CAS  Google Scholar 

  168. Defronzo RA. Bromocriptine: a sympatholytic, d2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care. 2011;34:789–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Starrenburg FC, Bogers JP. How can antipsychotics cause diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins. Eur Psychiatry. 2009;24:164–70.

    Article  PubMed  CAS  Google Scholar 

  170. Donovan MH, Tecott LH. Serotonin and the regulation of mammalian energy balance. Front Neurosci. 2013;7:1–15.

    Article  CAS  Google Scholar 

  171. Fletcher PJ, Paterson IA. A comparison of the effects of tryptamine and 5-hydroxytryptamine on feeding following injection into the paraventricular nucleus of the hypothalamus. Pharmacol Biochem Behav. 1989;32:907–11.

    Article  PubMed  CAS  Google Scholar 

  172. Leibowitz SF, Weiss GF, Suh JS. Medial hypothalamic nuclei mediate serotonin’s inhibitory effect on feeding behavior. Pharmacol Biochem Behav. 1990;37:735–42.

    Article  PubMed  CAS  Google Scholar 

  173. Fetissov SO, Meguid MM. Serotonin delivery into the ventromedial nucleus of the hypothalamus affects differently feeding pattern and body weight in obese and lean zucker rats. Appetite. 2010;54:346–53.

    Article  PubMed  CAS  Google Scholar 

  174. Breisch ST, Zemlan FP, Hoebel BG. Hyperphagia and obesity following serotonin depletion by intraventricular pchlorophenylalanine. Science. 1976;192:382–5.

    Article  PubMed  CAS  Google Scholar 

  175. Saller CF, Stricker EM. Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine. Science. 1976;192:385–7.

    Article  PubMed  CAS  Google Scholar 

  176. Waldbillig RJ, Bartness TJ, Stanley BG. Increased food intake, body weight, and adiposity in rats after regional neurochemical depletion of serotonin. J Comp Physiol Psychol. 1981;95:391–405.

    Article  PubMed  CAS  Google Scholar 

  177. Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. 2012;367:1577–9.

    Article  PubMed  CAS  Google Scholar 

  178. Berglund ED, Liu C, Sohn JW, Liu T, Kim MH, Lee CE, Vianna CR, Williams KW, Xu Y, Elmquist JK. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. J Clin Invest. 2013;123:5061–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Chen X, Margolis KJ, Gershon MD, Schwartz GJ, Sze JY. Reduced serotonin reuptake transporter (SERT) function causes insulin resistance and hepatic steatosis independent of food intake. PLoS One. 2012;7:e3251.

    Google Scholar 

  180. Ghaeli P, Shahsavand E, Mesbahi M, Kamkar MZ, Sadeghi M, Dashti-Khavidaki S. Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder. J Clin Psychopharmacol. 2004;24:386–8.

    Article  PubMed  CAS  Google Scholar 

  181. Iordanidou M, Tavridou A, Petridis I, Arvanitidis KI, Christakidis D, Vargemezis V, Manolopoulos VG. The serotonin transporter promoter polymorphism (5-HTTLPR) is associated with type 2 diabetes. Clin Chim Acta. 2010;411:167–71.

    Article  PubMed  CAS  Google Scholar 

  182. Furman BL, Wilson GA. Further studies on the effects of 5-hydroxytryptophan on plasma glucose and insulin in the mouse. Diabetologia. 1980;19:386–90.

    Article  PubMed  CAS  Google Scholar 

  183. Yamada J, Sugimoto Y, Kimura I, Takeuchi N, Horisaka K. Serotonin-induced hypoglycemia and increased serum insulin levels in mice. Life Sci. 1989;45:1931–6.

    Article  PubMed  CAS  Google Scholar 

  184. Hajduch E, Rencurel F, Balendran A, Batty IH, Downes CP, Hundal HS. Serotonin (5-hydroxytryptamine), a novel regulator of glucose transport in rat skeletal muscle. J Biol Chem. 1999;274:13563–8.

    Article  PubMed  CAS  Google Scholar 

  185. Fumeron F, Betoulle D, Nicaud V, Evans A, Kee F, Ruidavets JB, Arveiler D, Luc G, Cambien F. Serotonin transporter gene polymorphism and myocardial infarction: etude caste’moins de’ l’infarctus du myocarde (ECTIM). Circulation. 2002;105:2943–5.

    Article  PubMed  CAS  Google Scholar 

  186. Coto E, Reguero JR, Alvarez V, Morales B, Batalla A, Gonzalez P, Martin M, Garcia-Castro M, Iglesias-Cubero G, Cortina A. 5-hydroxytryptamine 5-HT2A receptor and 5-hydroxytryptamine transporter polymorphisms in acute myocardial infarction. Clinical Science. 2003;104:241–5.

    Article  PubMed  CAS  Google Scholar 

  187. Yuan X, Yamada K, Ishiyama-Shigemoto S, Koyama W, Nonaka K. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes. Diabetologia. 2000;43:373–6.

    Article  PubMed  CAS  Google Scholar 

  188. Rosmond R, Bouchard C, Bjorntorp P. Increased abdominal obesity in subjects with a mutation in the 5-HT2A receptor gene promoter. Ann N Y Acad Sci. 2002;967:571–5.

    Article  PubMed  CAS  Google Scholar 

  189. Wolff B, Grabe HJ, Volzke H, Ludemann J, Schwahn C, Freyberger H, John U, Langes M, Cascorbi I, Felix SB. A functional serotonin transporter (SLC6A4) polymorphism modifies the association of smoking and diabetes with asymptomatic carotid atherosclerosis. Thromb Haemost. 2005;93:180–2.

    PubMed  Google Scholar 

  190. Arinami T, Ohtsuki T, Yamakawa-Kobayashi K, Amemiya H, Fujiwara H, Kawata K, Ishiguro H, Hamaguchi H. A synergistic effect of serotonin transporter gene polymorphism and smoking in association with CHD. Thromb Haemost. 1999;81:853–6.

    PubMed  CAS  Google Scholar 

  191. Muldoon MF, Mackey RH, Korytkowski MT, Flory JD, Pollock BG, Manuck SB. The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers. J Clin Endocrinol Metab. 2006;91:718–21.

    Article  PubMed  CAS  Google Scholar 

  192. Muldoon MF, Mackey RH, Williams KV, Korytkowski MT, Flory JD, Manuck SB. Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity. J Clin Endocrinol Metab. 2004;89:266–71.

    Article  PubMed  CAS  Google Scholar 

  193. Muldoon MF, Mackey RH, Sutton-Tyrrell K, Flory JD, Pollock BG, Manuck SB. Lower central serotonergic responsivity is associated with preclinical carotid artery atherosclerosis. Stroke. 2007;38:2228–33.

    Article  PubMed  CAS  Google Scholar 

  194. Corona G, Ricca V, Bandini E, Rastrelli G, Casale H, Jannini EA, Sforza A, Forti G, Mannucci E, Maggi M. SIEDY scale 3, a new instrument to detect psychological component in subjects with erectile dysfunction. J Sex Med. 2012;9:2017–26.

    Article  PubMed  Google Scholar 

  195. Torner L, Toschi N, Pohlinger A, Landgraf R, Neumann ID. Anxiolytic and anti-stress effects of brain prolactin: improved efficacy of antisense targeting of the prolactin receptor by molecular modeling. J Neurosci. 2001;21:3207–14.

    PubMed  CAS  Google Scholar 

  196. Drago F, Continella G, Conforto G, Scapagnini U. Prolactin inhibits the development of stress-induced ulcers in the rat. Life Sci. 1985;36:191–7.

    Article  PubMed  CAS  Google Scholar 

  197. Drago F, Pulvirenti L, Spadaro F, Pennisi G. Effects of TRH and prolactin in the behavioral despair (swim) model of depression in rats. Psychoneuroendocrinology. 1990;15:349–56.

    Article  PubMed  CAS  Google Scholar 

  198. Fujikawa T, Soya H, Yoshizato H, Sakaguchi K, Doh-Ura K, Tanaka M, Nakasima K. Restraint stress enhances the gene expression of prolactin receptor long form at the choroid plexus. Endocrinology. 1995;136:5608–13.

    PubMed  CAS  Google Scholar 

  199. Walsh RJ, Slaby FJ, Posner BI. A receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid. Endocrinology. 1987;120:1846–50.

    Article  PubMed  CAS  Google Scholar 

  200. Theorell T Prolactin—a hormone that mirrors passiveness in crisis situations. Integr Physiol Behav Sci. 1992;27:32–8.

    Article  PubMed  CAS  Google Scholar 

  201. Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64:327–37.

    Article  PubMed  CAS  Google Scholar 

  202. Salamone JD, Aberman JE, Sokolowski JD, Cousins MS. Nucleus accumbens dopamine and rate of responding: neurochemical and behavioral studies. Psychobiology. 1999;27:236–47.

    CAS  Google Scholar 

  203. Neill DB, Fenton H, Justice JB. Increase in accumbal dopaminergic transmission correlates with response cost not reward of hypothalamic stimulation. Behav Brain Res. 2002;137:129–38.

    Article  PubMed  CAS  Google Scholar 

  204. Papp M, Klimek V, Willner P. Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine. Psychopharmacology. 1994;115:441–6.

    Article  PubMed  CAS  Google Scholar 

  205. Ichikawa J, Meltzer HY. Effect of antidepressants on striatal and accumbens extracellular dopamine levels. Eur J Pharmacol. 1995;281:255–61.

    Article  PubMed  CAS  Google Scholar 

  206. Randrup A, Munkvad I, Fog R, Gerlach J, Molander L, Kielberg B, Scheel-Kruger J. Mania, depression and brain dopamine. In: Essman WB, Valzelli S, editors. Current developments in psychopharmacology. New York: NY Spectrum Publications; 1975. p. 206–48.

    Google Scholar 

  207. Banki CM. Correlation between cerebrospinal fluid amine metabolites and psychomotor activity in affective disorders. J Neurochem. 1977;28:255–7.

    Article  PubMed  CAS  Google Scholar 

  208. Bowers Jr MB, Heninger GR, Gerbode F. Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in psychiatric patients. Int J Neuropharmacol. 1969;8:255–62.

    Article  PubMed  CAS  Google Scholar 

  209. Mendels J, Frazer A, Fitzgerald RG, Ramsey TA, Stokes JW. Biogenic amine metabolites in cerebrospinal fluid of depressed and manic patients. Science. 1972;175:1380–2.

    Article  PubMed  CAS  Google Scholar 

  210. Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR, Charney DS. Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Arch Gen Psychiatry. 1996;53:117–28.

    Article  PubMed  CAS  Google Scholar 

  211. Monreal J, Duval F, Mokrani MC, Pinault G, Macher JP. Exploration de la fonction dopaminergique dans les depressions bipolares et unipolares. Ann Med Psychol (Paris). 2005;163:399–404.

    Article  Google Scholar 

  212. McPherson H, Walsh A, Silverstone T. Growth hormone and prolactin response to apomorphine in bipolar and unipolar depression. J Affect Disord. 2003;76:121–5.

    Article  PubMed  CAS  Google Scholar 

  213. Post RM, Gerner RH, Carman JS, Gillin JC, Jimerson DC, Goodwin FK, Bunney Jr WE. Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response. Arch Gen Psychiatry. 1978;35:609–15.

  214. Nordin C, Siwers B, Bertilsson L. Bromocriptine treatment of depressive disorders. Clinical and biochemical effects. Acta psychiatr. Scand. 1981;64:25–33.

    CAS  Google Scholar 

  215. Waehrens J, Gerlach J. Bromocriptine and imipramine in endogenous depression. A double-blind controlled trial in out-patients. J Affect Disord. 1981;3:193–202.

    Article  PubMed  CAS  Google Scholar 

  216. Bouras N, Bridges P. Bromocriptine in depression. Curr Med Res Opin. 1982;8:150–3.

    Article  PubMed  CAS  Google Scholar 

  217. Theohar C, Fischer-Cornelssen K, Brosch H, Fischer E, Petrovic D. A comparative, multicenter trial between bromocriptine and amitriptyline in the treatment of endogenous depression. Arzneimittelforschung. 1982;32:783–7.

    PubMed  CAS  Google Scholar 

  218. Izumi T, Inoue T, Kitagawa N, Nishi N, Shimanaka S, Takahashi Y, Kusumi I, Odagaki Y, Denda K, Ohmori T, Koyama T. Open pergolide treatment of tricyclic and heterocyclic antidepressant-resistant depression. J Affect Disord. 2000;61:127–32.

    Article  PubMed  CAS  Google Scholar 

  219. Bouckoms A, Mangini L. Pergolide: an antidepressant adjuvant for mood Disorders? Psychopharmacol Bull. 1993;29:207–11.

    PubMed  CAS  Google Scholar 

  220. Inoue T, Tsuchiya K, Miura J, Sakakibara S, Denda K, Kasahara T, Koyama T. Bromocriptine treatment of tricyclic and heterocyclic antidepressant-resistant depression. Biol Psychiatry. 1996;40:151–3.

    Article  PubMed  CAS  Google Scholar 

  221. Kalia M Neurobiological basis of depression: an update. Metabolism. 2005;4:24–7.

    Article  CAS  Google Scholar 

  222. Åsberg M, Nordström P, Träskman-Bendz L. Cerebrospinal fluid studies in suicide. An Overview Ann NY Acad Sci. 1986;487:243–55.

    Article  PubMed  Google Scholar 

  223. Asberg M, Traskman L, Thoren P. 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry. 1976;33:1193–7.

    Article  PubMed  CAS  Google Scholar 

  224. Murphy DL, Campbell L, Costa JL. Current status of the indoleamine hypothesis of the affective disorders. In: Lipton MA, DiMascio A, Killam KF, editors. Psychopharmacology: a generation of progress. New York: Raven Press; 1978. p. 1235–47.

    Google Scholar 

  225. Meltzer HY, Lowy MT. The serotonin hypothesis of depression. In: Meltzer HY, editor. Psychopharmacology: the third generation of progress. New York: Raven Press; 1987. p. 513–26.

    Google Scholar 

  226. van Praag HM, de Hann S. Chemoprophylaxis of depression: an attempt to compare lithium with 5-hydroxytryptophan. Acta Psychiatr Scand. 1981;63:191–205.

    Article  Google Scholar 

  227. Newman ME, Shapira B, Lerer B. Evaluation of central serotonergic function in affective and related disorders by the fenfluramine challenge test: a critical review. Int J Neuropsychopharmacol. 1998;1:49–69.

    Article  PubMed  CAS  Google Scholar 

  228. Kapitany T, Schindl M, Schindler SD, Hesselmann B, Füreder T, Barnas C, Sieghart W, Kasper S. The citalopram challenge test in patients with major depression and in healthy controls. Psychiatry Res. 1999;88:75–88.

    Article  PubMed  CAS  Google Scholar 

  229. Malone KM, Corbitt EM, Li S, Mann JJ. Prolactin response to fenfluramine and suicide attempt lethality in major depression. Br J Psychiatry. 1996;168:324–9.

    Article  PubMed  CAS  Google Scholar 

  230. Gordon JA, Hen R. The serotonergic system and anxiety. Neruomol Med. 2004;5:27–40.

    Article  CAS  Google Scholar 

  231. Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P, Parsons LH, Tecott LH. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proc Natl Acad Sci U S A. 1998;95:15049–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  232. Parks CL, Robinson PS, Sibille E, Shenk T, Toth M. Increased anxiety of mice lacking the serotonin 1A receptor. Proc Natl Acad Sci U S A. 1998;95:10734–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  233. Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, Mendelsohn M, Mann JJ, Brunner D, Hen R. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci U S A. 1998;95:14476–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  234. Griebel G 5-hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. Pharmacol Therap. 1995;65:319–95.

    Article  CAS  Google Scholar 

  235. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D. Lesch KP. Allelic Variation of Human Serotonin Transporter Gene Expression J Neurochem. 1996;66:2621–4.

    PubMed  CAS  Google Scholar 

  236. Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry. 2010;167:509–27.

    Article  PubMed  PubMed Central  Google Scholar 

  237. Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR. A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry. 2005;62:146–52.

    Article  PubMed  CAS  Google Scholar 

  238. Pergamin-Hight L, Bakermans-Kranenburg MJ, van Ijzendoorn MH, Bar-Haim Y. Variations in the promoter region of the serotonin transporter gene and biased attention for emotional information: a meta-analysis. Biol. Psychiatr. 2012;71:373–9.

    Article  CAS  Google Scholar 

  239. Reist C, Mazzanti C, Vu R, Tran D, Goldman D. Serotonin transporter promoter polymorphism is associated with attenuated prolactin response to fenfluramine. Am J Med Genet. 2001;105:363–8.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy

    Giulia Rastrelli, Giovanni Corona & Mario Maggi

  2. Endocrinology Section, Maggiore Hospital, Largo Nigrisoli 2, 40133, Bologna, Italy

    Giovanni Corona

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  1. Giulia Rastrelli
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Correspondence to Mario Maggi.

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Original data derive from a cohort of patients attending the Outpatient Clinic of Sexual Medicine and Andrology Unit of the University of Florence. All the data provided were collected as part of the routine clinical procedure. An informed consent was obtained from all patients.

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Rastrelli, G., Corona, G. & Maggi, M. The role of prolactin in andrology: what is new?. Rev Endocr Metab Disord 16, 233–248 (2015). https://doi.org/10.1007/s11154-015-9322-3

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