Modulation of Hypothalamic Luteinizing Hormone-Releasing Hormone Levels by Intracranial and Subcutaneous Implants of Gonadal Steroids in Castrated Rats: Effects of Androgen and Estrogen Antagonists*

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Abstract
Castration-induced hypersecretion of pituitary LH was associated with a marked reduction in the medial basal hypothalamic (MBH) LHRH contents. Testosterone (T) therapy promptly reduced LH to intact serum levels within 24 h, while the MBH LHRH levels were restored only after 7 days. Withdrawal of T replacement caused hypersecretion of LH within 8 h, although the first significant decrease in the MBH LHRH contents occurred between days 4–7. The two metabolites of T, 5α-dihydrotestosterone (DHT) and 17β-estradiol (E2), were as effective as T in raising the MBH LHRH content; however, their effects on serum LH were variable. The antiandrogen flutamide, but not the antiestrogen nafoxidine hydrochloride, blocked the stimulatory effects of T and DHT on MBH LHRH levels. Nafoxidine treatment was also ineffective in reversing this central effect of E2. None of these treatments significantly altered LHRH content in the preoptic area (POA). In view of the wide distribution of LHRH-containing neurons in the septal POA and MBH, the effects of intracranial implantation of DHT, E2, and progesterone in the MBH or POA on hypothalamic LHRH content were evaluated. Similar to T action (5), DHT was effective only when placed in the MBH; E2 implants in the POA and MBH elevated the MBH LHRH levels. None of these steroids placed in the POA modified local levels of LHRH. These studies show that: 1) changes in hypothalamic LHRH are considerably more sluggish than are changes in serum LH after major alterations in serum T titers, 2) the enzymatic reduction of T to DHT may be an important prerequisite in the manifestation of its effects on the MBH LHRH content, 3) the MBH seems to be the major central site of action of gonadal steroids in modulating hypothalamic LHRH activity, and 4) since the POA LHRH neurons and their terminals in the organum vasculosum are unresponsive to steroids, it appears that there may be a distinct steroid-sensitive population of LHRH neurons which project into the median eminence. (Endocrinology106: 390, 1980)

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