Inhibitory feedback action of gonadal steroids at the hypothalamic level

Do inhibitory effects of intrahypothalamic implantation of crystalline steroids on gonadotropins (GTHs) depend on spread of steroid to the pituitary (AP) rather than direct action at the hypothalamic level? If so, such implants should reduce AP sensitivity to releasing factors (RF) by the time the decline in plasma GTHs occurs. 200μg 'pellets' of testosterone propionate (TP) were implanted in the median eminence of castrated adult male rats and measurements were made of plasma LH(RIA) before and 10 min after iv injection of synthetic LHRF. LH dropped from 472±44ng RP l/ml preoperatively to 105±18ng 1 day (d) later, and to 30±4ng 3ds later. At 3ds, 1 and 10ng LHRF raised LH to 184±46 and 339±69ng, respectively. At that time cholesterol controls showed only a slight drop in LH from 421±40 to 338±37ng, and the 2 LHRF doses increased LH to 649±114 and 1069±237ng, respectively. To study the immediate events after TP implantation, hourly samples were taken. A significant decline in LH was observed by 3 h, while control values rose; however, the response to 10ng LHRF was unimpaired at 6h (post minus pre LHRF values:720±92 ng TP, 670±129ng Chol). It is concluded that, as LH secretion seems to drop before AP sensitivity to LHRF is affected, hypothalamic TP must act by decreasing endogenous LHRF production. Any subsequent decline in AP sensitivity may be presumed to result from this initial effect. Similar experiments with various steroids in females are reported.