ANDROGEN INHIBITS THE INCREASES IN HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE (CRH) AND CRH-IMMUNOREACTIVITY FOLLOWING GONADECTOMY

To characterize the effect of androgens on the hypothalamo-pituitary-a drenal (HPA) axis we examined the regulation of corticotropin-releasin g hormone (CRH) following gonadectomy and hormone replacement. Three-m onth-old male Fischer 344 (F344) rats were gonadectomized (GDX) or sha m GDX. Control animals remained intact. Animals were sacrificed 1, 4, 7, 10, or 21 days following surgery. GDX rats had significantly elevat ed (p<0.05) levels of hypothalamic CRH 21 days after surgery compared to intact and sham-operated rats. In a second study, 3-month-old male F344 rats were GDX and treated with the non-aromatizable androgen, dih ydrotestosterone (DHT), using a Silastic capsule containing crystallin e DHT propionate subcutaneously implanted in each animal's back. Contr ol animals were GDX and sham-treated or left intact (INT). Three weeks following gonadectomy, CRH levels in the hypothalamus of GDX rats sho wed a significant increase (p<0.05) compared to intact animals. DHT tr eatment, beginning at the time of gonadectomy prevented this increase. CRH or arginine vasopressin (AVP) immunoreactivity was examined using immunocytochemistry. The number of CRH-immunoreactive (IR) cells in t he paraventricular nucleus (PVN) of GDX, DHT-treated animals was signi ficantly decreased (p<0.05) compared to GDX rats. No differences were seen between treatment groups in CRH-IR cell numbers in the bed nucleu s of the stria terminalis or the central amygdaloid nucleus or in AVP- IR cell numbers in the PVN. These data demonstrate that long-term cast ration increases hypothalamic CRH content and CRH-IR cell numbers in t he PVN by removal of an androgen-dependent repression.