A Medial Basal Hypothalamic Site of Synergistic Action of Estrogen and Progesterone on the Inhibition of Pituitary Luteinizing Hormone Release1

Abstract

Plasma LH concentrations were measured by radioimmunoassay in blood withdrawn from indwelling atrial cannulas in long-term ovariectomized (OVX) rats. Subcutaneous injection of 50 μg of estradiol benzoate (EB) in oil depressed the plasma LH concentration to about one-third within 2 h. In other rats, sc injection of 25 mg of progesterone (P) in oil at the time of EB injection did not alter this response. Plasma LH remained suppressed at that level until at least 8 h after injection in both groups, but fell an additional 50% within 24 h after injection only in the rats treated with both EB and P. In additional rats, P, but not the oil vehicle alone, when administered 18 h after the injection of EB, caused plasma LH to decline by about 50% within 60 min. Under these latter conditions, 5, 20 or 100 ng of LHRH was injected through the cannula at 1 h after the injection of P or oil. Progesterone did not inhibit pituitary LH release in response to LHRH as determined by comparison of plasma LH concentrations and increments at 3, 10 and 30 min after LHRH in the two groups. In OVX rats which still exhibited pulsatile LH release after surgical interruption of all of the neural connections to their medial basal hypothalami, injection of EB followed 18 h later by injection of P produced results similar to those seen in control OVX rats. The results suggest that P acts synergistically with estrogen at the level of the medial basal hypothalamus in long-term OVX rats to lower plasma LH concentrations to levels which approach but do not reach basal plasma LH levels in cyclic rats and that, under the conditions of this study, P does not lower plasma LH concentration in EB-treated OVX rats until estrogen has exerted its effect for >8 h but ≤18 h.