Direct Pituitary Effects of Estrogen and Progesterone on Gonadotropin Secretion in the Ovariectomized Ewe

Abstract

The direct pituitary effects of estrogen and progesterone on the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in ovariectomized (OVX) ewes in which the pituitary had been disconnected surgically from the hypothalamus (hypothalamo-pituitary disconnection, HPD). Gonadotropin secretion was restored with hourly pulses of 500 ng gonadotropin-releasing hormone (GnRH) via intra-atrial cannulae. Intramuscular injections of 50 µg estradiol benzoate (EB) to 5 sheep initially caused reductions (∼5O%) in plasma LH baseline, peak values and LH pulse amplitude. Therafter all parameters of plasma LH concentration increased 2- to 3-fold above starting values. After these 5 sheep had received 2 subcutaneous progesterone implants (mean ± SEM plasma levels 5.3 ± 1.5 nmol/1), the biphasic LH response to EB was still apparent and increases in LH peak values (267 ± 19%) and LH pulse amplitudes (262 ± 23%) were greater (p < 0.05) than those seen with EB alone (195 ± 11 and 172 ± 14%, respectively). The presence of 2 progesterone implants alone did not change plasma LH baseline, peak values or pulse amplitude, or plasma FSH values. In the second experiment, where 4 OVX-HPD ewes were given 4 progesterone implants (plasma progesterone 27.7 ± 3.4 nmol/l), there were no effects on basal plasma LH or plasma FSH values. The LH responses to EB were more marked in 4 OVX-HPD ewes given 4 progesterone implants than in the animals given EB alone. Also, the estrogen-induced LH surge occurred earlier in the ewes given 4 progesterone implants than in those given estrogen alone. The addition of 2 or 4 subcutaneous progesterone implants did not affect estrogen-induced suppression of FSH secretion in GnRH-pulsed OVX-HPD ewes. These data indicate that estrogen has a direct pituitary effect to influence the action of GnRH and that progesterone alone does not influence the secretion of LH or FSH by a direct pituitary effect. Progesterone may enhance the feedback effects of estrogen on LH secretion by a direct action at the pituitary level.