Peripheral and central sex steroids have differential effects on the HPA axis of male and female rats.

Sex differences in hypothalamic-pituitary-adrenal (HPA) function were examined in gonadectomized male and female rats given equivalent sex hormone replacement regimens either using subcutaneous silastic implants (Experiment 1) or cannula implants in the medial preoptic area (MPOA) (Experiment 2) containing either dihydrotestosterone (DHT), testosterone propionate (TP), estradiol benzoate (EB), or left empty (control). Plasma was obtained before and after 20 min of restraint stress to determine plasma ACTH, corticosterone, and CBG levels as measures of HPA function. Consistent with the literature, androgens decreased, and estrogen increased these measures of HPA function, although peripheral implants were more effective than MPOA implants. Gonadectomy and sex hormone treatment did not eliminate sex differences; overall, females had higher levels than males on measures of HPA function. Analyses of variance (ANOVA) indicated interactions of sex and sex hormone treatment on CBG levels and post-stress corticosterone levels in Expt. 1. The results suggest that sexual dimorphisms influence HPA function even when males and females are given equivalent physiological doses of gonadal steroids, and that the relevant sexual dimorphisms involve both the periphery and the CNS.