An Analysis of the Negative Feedback Control of Gonadotropin Secretion Utilizing Chronic Implantation of Ovarian Steroids in Ovariectomized Rhesus Monkeys12

The role of ovarian steroids in the negative feedback inhibition of gonadotropin secretion was examined in rhesus monkeys which were ovariectomized and simultaneously implanted sc with Silastic capsules containing either estradiol 17β or estradiol plus progesterone. By varying the number and dimensions of the capsules implanted, predetermined plasma concentrations of these steroids could be successively achieved and maintained within the physiological range for any desired length of time with the objective of determining the sensitivity of the negative feedback system to known circulating levels of estradiol and progesterone. Maintenance of circulating estradiol alone, within the range observed before ovariectomy (50-80 pg/ml), was usually insufficient to prevent the rise in circulating LH and FSH following ovariectomy whereas maintenance of preoperative plasma levels of both estradiol and progesterone suppressed gonadotropins to undetectable levels. In monkeys treated with estradiol alone, step increments or decrements of 20 to 30 pg/ml from threshold estradiol concentrations elicited large but reversible changes in circulating LH. Circulating estradiol levels which were insufficient to maintain low plasma LH concentrations during the period immediately following ovariectomy were, in some individuals, subsequently effective in this regard. In every monkey whose experimentally imposed estrogen levels were 50 pg/ml or above, but insufficient to maintain circulating LH within the preoperative range, the introduction of physiological plasma levels of progesterone was associated with a decline in circulating LH to precastration levels or below. Progesterone by itself or in combination with plasma estradiol concentrations below 30 pg/ml did not elicit a major suppression in circulating LH. These studies indicate that the negative feedback regulation of LH secretion in the rhesus monkey is a finely tuned system with a set-point which appears to change as a function of time after castration. Further, progesterone can synergize with subthreshold levels of estradiol in suppressing LH secretion in the ovariectomized monkey, but the relevance of these findings to the negative feedback control of the normal ovarian cycle remains to be determined. (Endocrinology93: 478, 1973)