• Testosterone’s regulation of the HPA axis differs for adolescent and adult male rats

      Zeidan, Mostafa; Department of Biological Sciences
      Stress hormones such as corticosterone (CORT), enables rodents to cope and meet the demands of their environment. In adult male rats, CORT release in response to stressors is dampened by the gonadal hormone testosterone. Adolescent male rats secrete more CORT in response to stressors than do adults and our lab has previously reported that gonadectomised pre-pubertal adolescent male rats (postnatal day [P] 35) do not show the dampening effect of testosterone replacement on CORT release in response to restraint stress found in adult rats (postnatal day [P] 75); whereas, post-pubertal adolescent rats (postnatal day [P] 45) show heightened CORT release when given testosterone replacement. Therefore, the main question would be what is the basis of the age difference in response to testosterone? And so, my mechanistic hypothesis that is tested in the thesis is that the greater stress response of adolescents than adults is because of greater conversion of testosterone to estradiol and/or less conversion of testosterone to DHT in adolescents than in adults. In Experiment 1, I replicated the results for P45 and P75 male rats. In Experiment 2, rats were gonadectomised (GDX) and given implants of testosterone, dihydrotestosterone (DHT), or empty, control implants (CTL) and plasma was obtained after 30 minutes of restraint. Although no significant differences were obtained for CORT levels, the pattern of means was consistent with our previous findings. Further, DHT and testosterone-treated rats had lower vasopressin (AVP) and corticotrophin releasing hormone (CRH), and a trend toward lower aromatase-immunoreactive cell counts in the parvocellular paraventricular nucleus (PVN) than did CTL rats, irrespective of age, and there were no group differences in the magnocellular PVN. In Experiment 3, gonadally-intact P45 and P75 males were treated with fadrozole (aromatase inhibitor), finasteride (5a-reductase inhibitor), flutamide (androgen receptor antagonist), or vehicle (VEH). Higher CORT concentrations after restraint were found in P45 than in P75 only among VEH rats. Among P45 rats, CORT levels were higher in VEH than in fadrozole-treated rats only. Among P75 rats, VEH rats had lower CORT levels than did finasteride-treated rats. These results suggest that the higher stress release of CORT in P45 may involve greater conversion of testosterone to estradiol at the level of the adrenal cortex.