Age‐dependent regulation by androgens of gene expression in the anterior hypothalamus and stress‐induced release of adrenal hormones in adolescent and adult male rats

The study investigated how testosterone regulates the hypothalamic-pituitary-adrenal (HPA) axis in response to stress in adolescent and adult male rats. It found that adolescents had higher post-stress corticosterone levels than adults, despite similar testosterone levels. Testosterone replacement increased corticosterone in adolescents but decreased it in adults. The age difference in corticosterone release was linked to greater conversion of testosterone to estradiol in adolescents and to dihydrotestosterone in adults. Inhibiting aromatase reduced corticosterone in adolescents, while inhibiting 5α-reductase or using an androgen receptor antagonist increased it in adults. These findings suggest that developmental changes in testosterone metabolism and gene expression regulation contribute to age-related differences in stress responses.