Elsevier

Hormones and Behavior

Volume 60, Issue 5, November 2011, Pages 691-698
Hormones and Behavior

Inhibiting influence of testosterone on stress responsiveness during adolescence

https://doi.org/10.1016/j.yhbeh.2011.09.007Get rights and content

Abstract

The maturation of the hypothalamo-pituitary-adrenal (HPA) axis is a key-component of the changes that occur during adolescence. In guinea pigs, HPA responsiveness during late adolescence depends strongly on the quantity and quality of social interactions: Males that lived in a large mixed-sex colony over the course of adolescence exhibit a lower stress response than males that were kept in pairs (one male/one female). Since colony-housed males have higher testosterone (T) levels than pair-housed males, and inhibiting effects of T on HPA function are well known, we tested the hypothesis that the decrease in stress responsiveness found in colony-housed males is due to their high T concentrations. We manipulated T levels in two experiments: 1) gonadectomy/sham-gonadectomy of colony-housed males (which usually have high T levels), 2) application of T undecanoate/vehicle to pair-housed males (which usually have low T levels). As expected, gonadectomized males showed a significantly increased stress response in comparison with sham-gonadectomized males, and T-injected males had a significantly lower stress response than vehicle-injected males. Both experiments thus confirm an inhibiting effect of T on HPA responsiveness during adolescence, which can mediate the influence of social interactions. The reduction in stress responsiveness is hypothesized to have a biologically adaptive value: A sudden increase in glucocorticoid concentrations can enhance aggressive behavior. Thus, pair-housed males might be adapted to aggressively defend their female (‘resource defense strategy’), whereas colony-housed males display little aggressive behavior and are capable of integrating themselves into a colony (‘queuing strategy’).

Highlights

► We manipulated testosterone (T) concentrations in male guinea pigs during adolescence. ► In late adolescence, we examined cortisol responsiveness. ► Males with high T values during adolescence had low cortisol response and vice versa. ► Thus, T has an inhibiting effect on cortisol responsiveness during adolescence. ► Adolescence may be a switch point for the adaptive modulation of the stress response.

Introduction

Adolescence is the gradual transition from infancy to adulthood and generally considered a very vulnerable life stage (Dahl, 2004, McCormick and Mathews, 2010): Many psychological disorders manifest for the first time during adolescence (Paus et al., 2008), and mortality is disproportionately high (Forbes and Dahl, 2010). These issues may be favored by the complex interplay of changes in the brain, in the endocrine systems, and in behavior that are typical for this phase of life (Blakemore, 2008, Forbes and Dahl, 2010, Sisk and Zehr, 2005, Yurgelun-Todd, 2007). More recently, the hypothesis emerged that said changes do not only make the adolescent more vulnerable towards adverse experiences, but also may represent an opportunity for adaptation to the current social environment (Dahl, 2004, McCormick et al., 2008, Sachser et al., 2011, Williams et al., 2001).

A key component of the age-related changes is the maturation of the hypothalamo-pituitary-adrenal (HPA) axis (Romeo, 2010b), which is one of the systems that are involved in the response towards stressors. On the one hand, it appears that adolescence is a very stressful life stage almost by definition due to the variety of changes and therefore constantly threatened homeostasis (Spear, 2000). Confirming this assumption, there is a body of literature that finds prolonged or higher stress responsiveness as well as heightened anxiety behavior in various species (reviewed by Spear, 2000, McCormick and Mathews, 2010).

On the other hand, there are some indicators that, during this time, stress responsiveness may actually be blunted: In periadolescent mice, the HPA response to novelty is lower than in adults (Adriani and Laviola, 2000), and periadolescent rats have a lower, although prolonged, corticosterone response compared with adult males (McCormick et al., 2008). In guinea pigs, late adolescent males display a decreased stress response towards novelty (Hennessy et al., 2006), a phenomenon that is influenced strongly by the social environment: Only males that are born and reared in large mixed-sex colonies show this reduction, whereas males that have been reared under pair-housing conditions with only one female after weaning have a higher stress response (Kaiser et al., 2007). These findings suggest that the reduction in stress responsiveness might be due to the amount of social stimulation an animal receives during adolescence. In two recent studies (Lürzel et al., 2010, Lürzel et al., 2011), we tested this hypothesis by experimentally manipulating the number of social interactions and confirmed that it is indeed the high amount of social stimulation a colony-housed male guinea pig receives during late adolescence that causes a lowered stress response to novelty.

The question of how this influence of the social environment is mediated is not yet answered. There are two arguments that speak for androgens as mediators: First, inhibiting effects of testosterone (T) on HPA function are widely known (El Hani et al., 1980, Gaskin and Kitay, 1971, Handa et al., 1994a, Seale et al., 2004). Second, social interactions have an enhancing effect on T secretion in a variety of species (Goymann et al., 2003, Harding, 1981, Hirschenhauser and Oliveira, 2006, van der Meij et al., 2008). In guinea pigs, there is a peak in T concentrations during late adolescence in colony-housed males (Sachser and Pröve, 1988), and in adulthood, colony-housed males have higher T levels than pair-housed males (Sachser, 1990). Thus, it only stands to reason that the high amount of social stimulation received by colony-housed males increases their T concentrations, and indeed, we could recently show that T levels increase after contact to unfamiliar conspecifics of both sexes (Lürzel et al., 2010, Lürzel et al., 2011). However, all evidence for a possible relationship between high T levels and a decreased stress response has been only correlative up to now.

The present project investigates in guinea pigs whether T indeed has an inhibitory effect on stress responsiveness during adolescence. To this purpose, two independent experiments were conducted. In Experiment 1, colony-housed males were either gonadectomized (GDX) or sham-gonadectomized (SHAM) during early adolescence (before puberty). Since there is no T in GDX over the course of adolescence, they are expected to have a higher stress response than SHAM in late adolescence. In Experiment 2, pair-housed males were injected with either a T depot (TM) or with vehicle (VM). In this case, we expected TM to have a decreased stress response in comparison with VM in late adolescence.

Section snippets

Animals and housing conditions

The guinea pigs (Cavia aperea f. porcellus) used were descendants of a heterogeneous shorthaired and multicolored stock of 40 animals obtained from a breeder in 1975. Experimental animals were derived from two mixed-sex colonies housed in the same room. The colonies consisted of 8–10 males and 13–15 females as well as their offspring, and showed a graduated age structure ranging from approximately 1 to 19 months. Each colony was housed in a wooden enclosure of approximately 6 m2.

All animals could

Experiment 1—Gonadectomy and stress responsiveness of colony-housed males

For basal testosterone (T) values (Fig. 2), ANOVA revealed a main effect of age (n = 9; F(1.29, 20.62) = 17.56, p < 0.001), a main effect of group (F(1, 16) = 55.13, p < 0.001), and an interaction of age and group (F(1.29, 20.62) = 36.05, p < 0.001). Subsequent t-tests found no differences on day 39 (t =  0.53, p = 0.985), but significantly lower T values in gonadectomized (GDX) than in sham-gonadectomized animals (SHAM) on days 55 and 120 (day 55: t =  10.09, p < 0.001; day 120: t =  6.99, p < 0.001). In GDX, there

Discussion

We hypothesized that the reduction in stress responsiveness found in late adolescent colony-housed male guinea pigs is mediated by high levels of androgens. In order to test this assumption, we manipulated testosterone (T) concentrations in guinea pigs under different housing conditions. In Experiment 1, we gonadectomized colony-housed males, which usually have relatively high T levels (Sachser, 1990); in Experiment 2, we injected pair-housed males, which have relatively low T levels (Sachser,

Acknowledgments

We would like to thank Sabine Kruse and Tanja Möllers for conducting the endocrine analyses. This research was funded by the German Research Foundation with a grant to N. S. (FOR 1232/Sa389/11-1) and by a stipend to S. L. by the Otto Creutzfeld Center for Cognitive and Behavioral Neuroscience.

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