Positive Feedback Effect of Progesterone on Luteinizing Hormone (LH) Release in Cyclic Female Rhesus Monkeys: LH Response Occurs in Two Phases*

Abstract

The synergistic effects of progesterone (P) and estrogen on LH release were examined in nine monkeys with regular menstrual cycles. During six menstrual cycles, animals were subjected, in alternate cycles, to each of the following treatments in random order beginning at 0830 on the third day of the cycle: 1) 30 <g estradiol benzoate (EB) sc, 2) 30 jug EB sc, followed by 2.5 mg P sc 24 h later, or 3) 330 <g EB sc. During the seventh menstrual cycle, all animals were assigned again to either treatment 1 or 2. Blood samples were obtained at 3- to 24-h intervals, and serum concentrations of LH, estradiol, and P were determined by RIA. The high dose of EB induced the characteristic negative feedback response of serum LH, followed by the positive feedback response which peaked 36–54 h after EB, while the low dose of EB induced initial small decreases of LH within 24 h after EB, followed by slight increases of LH during the second and third days after EB. P administration after the low dose of EB induced two distinct phases of an LH response: an early release of LH, the peak of which appeared within 24 h after P, and a later release of LH, the peak of which appeared more than 24 h after P. The early release of LH began within 3 h after P, reached a peak 6–12 h after P, and lasted for 12–18 h; this response was significantly higher than that induced by the low dose of EB alone (P « 0.001). In addition to the elevated concentrations of circulatory estrogen and P due to exogenous hormone administration, a secondary increase of estradiol after the increase of LH was evident in animals responding with an early peak of LH. The late release of LH began 24 h after P, peaked 30–48 h after P, and lasted for 24–60 h. It also was significantly greater than that induced by the low dose of EB alone (P < 0.025). No secondary increases of ovarian steroids were observed in animals responding with a late peak of LH. Increases of FSH during the early and late releases of LH were evident, although not statistically significant. Thus, P injection after a subthreshold dose of estrogen during the early follicular phase can induce two phases of LH release in the rhesus monkey. These observations indicate that during the periovulatory phase, P may play an important role in facilitating the release of LH in primates.