Feedback effects of ovarian steroids on the hypothalamic-hypophyseal axis in the rabbit

Abstract

The feedback effects of two ovarian steroids, estradiol-17β (E2) and 20α-hydroxypregn-4-en-3-one (20αOH), were examined in both intact (INT) and ovariectomized (OVEX) does. We measured (1) steroid-induced alterations in endogenous gonadotropin-releasing hormone (GnRH) from sequential 10-min samples of hypothalamic perfusates, (2) simultaneous changes in peripheral plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and (3) the modification of pituitary responsiveness, i.e., increments in plasma LH (Δ LH) and plasma FSH (Δ FSH), after 50 ng, 250 ng, and 1 μg of exogenous GnRH in individual does of 6 treatment groups. The groups were: INT does, OVEX does, OVEX does receiving either one (1 E2) or two (2 E2) E2-filled Silastic capsules, OVEX does receiving a 20αOH-filled capsule (20αOH), and OVEX does receiving both capsules of E2 and 20αOH (1 E2 + 20αOH). Ovariectomy enhanced the pulsatile release of hypothalamic GnRH and pituitary LH and FSH, and increased the LH response (Δ LH) to exogenous GnRH (OVEX vs. INT, p<0.05). Replacement of E2 at the time of ovariectomy prevented the increased GnRH and gonadotropin secretion as well as the enhanced Δ LH that were observed in untreated OVEX does. The release of hypothalamic GnRH in the 20αOH group was lower (p<0.05) than that in the OVEX group and not different from that in the INT group. The release of pituitary LH and FSH and the Δ LH in the 20αOH group was not different from that in the OVEX group, but these parameters were greater (p<0.05) than those in the INT group. The hypothalamic GnRH pulse frequency in the 1 E2 + 20αOH group was lower (p<0.05) than that in either the 1 E2 or the 20αOH group, but the Δ LH in the 1 E2 + 20αOH group was not different from that in either the 1 E2 or the 20αOH group. The highest dose (1 μg) of exogenous GnRH stimulated a modest increase in FSH in the OVEX, 20αOH, 1 E2 + 20αOH, and 1 E2 groups; but a steroid effect on Δ FSH among these 4 groups was not apparent. These results suggest that in the rabbit, E2 exerts its inhibitory effects on both the hypothalamus and the pituitary, whereas 20αOH suppresses hypothalamic GnRH release and facilitates pituitary LH responsiveness.