Estrogenic feminization of the LH response to orchidectomy in the rat: evidence for a hypothalamic site of action.

These studies were conducted to determine the possible site of action at which estrogen "feminizes" the pituitary luteinizing hormone (LH) response to orchidectomy (ORDX). When Silastic implants containing estradiol-17 beta (E2) were inserted 1 day prior to ORDX and subsequently removed 5 days later, characteristic increases in plasma LH and follicle-stimulating hormone (FSH) levels normally observed within 24 h after ORDX were completely (for LH) or partially (for FSH) prevented. Rather, gonadotropin patterns, especially LH, resembled patterns seen during a similar time interval after ovariectomy of female rats in diestrus-1, that is, increases in plasma FSH unaccompanied by rises in plasma LH. Although castration-induced increments in plasma gonadotropin levels were abated by prior E2 treatment of orchidectomized male rats, the responsiveness of the anterior pituitary gland to two intravenous pulse injections of luteinizing hormone-releasing hormone (LHRH) tested 6 and 8 h after removal of E2 capsules was markedly greater than pituitary LH responses to both pulse injections at similar times following ORDX. Pituitary FSH responses in E2-treated orchidectomized rats were higher only after the second LHRH injection. To determine whether the increased pituitary responsiveness to LHRH was actually due to the E2 treatment or to the concomitant orchidectomy, pituitary LH and FSH responses to a single LHRH pulse injection were evaluated 10 h after removal of either E2 or empty capsules from 4-day orchidectomized rats in which these capsules had been inserted 1 day prior or ORDX. It was found that pituitary LH responses to LHRH were greatly increased 4 days after ORDX. Moreover, mean maximal increments in LH and FSH were significantly higher in ORDX-E2-treated castrated rats. Therefore, the data indicate that E2 delays the onset of increases in plasma LH and to a lesser extent FSH concentrations after ORDX ("feminization") by acting within the hypothalamus to inhibit the release of LHRH from peptidergic neurons.