The Negative Feedback Control by Estradiol and Progesterone of LH Secretion in the Ovariectomized Rhesus Monkey12

Abstract

The pulsatile, circhoral discharges of LH observed in ovariectomized rhesus monkeys were blocked within min following single intravenous injections of 17P-estradiol or the initiation of estradiol infusions which achieved physiologic plasma levels of the steroid. The resulting depression in plasma LH concentrations was maintained for several hr after circulating estrogen levels had declined to undetectable values. Pulsatile LH discharges resumed abruptly following this period of inhibition but with a lower frequency and larger magnitude. In contrast, intravenous injections of progesterone had no effect on LH secretion unless massive doses were given, with resultant plasma concentrations of the steroid a thousand fold greater than luteal phase levels. These but caused irregularities in the circhoral rhythm. Similarly, the daily subcutaneous administration of progesterone, in oil, for 2 weeks failed to reduce the elevated plasma LH concentrations in ovariectomized animals. It is concluded that estrogen is the principal participant in the negative feed-back control of tonic LH secretion in primates and that progesterone alone is physiologically inert in this regard. {Endocrinology 90: 771, 1972) W HILE THE NEGATIVE feed-back relationship between the production of the gonadal steroids and the pituitary gonadotropic hormones has been firmly established for some decades, the dynamics of this system as well as the specificity of the interrelationships involved have remained obscure. The advent of radioimmunoassays for the gonadotropins and for the gonadal hormones as well as related techniques for the measurement of circulating steroids has permitted new approaches to this problem. In the rhesus monkey, we have recently shown that gonadectomy results in significant elevations in plasma LH concentrations, within 2 days after the operation. LH levels continue to rise until they reach a plateau,

Episodic Luteinizing Hormone Secretion in Man PULSE ANALYSIS, CLINICAL INTERPRETATION, PHYSIOLOGIC MECHANISMS

“…To One of the most striking changes in LH secretion occurs between the follicular and the luteal phases of the menstrual cycle when there is a shift from high frequency, low amplitude to low frequency, high amplitude secretory spikes. It is of interest that similar low frequency, high amplitude pulses were observed in both castrate monkeys (12) and in patients with gonadal dysgenesis recovering from estrogen-induced gonadotropin suppression (26). In these studies, estrogen infusions resulted in blood levels similar to or exceeding those which occur before the midcycle LH peak in women.…”

“…The rhythmic secretion of LH at 1-to 3-h intervals has been described for several species (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In man, pulsatile LH secretion has been observed in normal men and women and in individuals with gonadal failure (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)14).…”

“…However, several investigators have recently demonstrated that LH is secreted in a pulsatile fashion in man as well as in other species (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Studies in monkeys (11) suggested that the stimuli inducing LH pulses originate in central nervous system centers which mediate these effects through neurons utilizing catecholamines as neurotransmitters.…”

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

“…The slight delay in the onset of in vivo as compared to in vitro effects is caused, in all probability, by the time needed for the steroid injected in periphery to reach an effective concentration at its target site(s). Indeed, acute intravenous injections of estradiol lead to a maximal estrogen concentration 5 min after the injection [287]. Furthermore, an early report on fast actions of estrogen showed that it takes about 15-16 min for significant changes in the firing rate of preoptic-hypothalamic neurons to be observed following a single intravenous injection of estradiol in ovariectomized females.…”

Neuroendocrine control of ovarian function in the primate

“…1), the daily blood hormone concentrations suggest uneventful secretory patterns for gonadotrophins, except at the time of the mid-cycle surge. However, frequent blood sampling clearly reveals that LH and FSH release from the pituitary does not occur at a continuous and steady rate but is the result of intermittent discharges of the hormones (Yamaji, Dierschke, Bhattacharya & Knobil, 1972 (From Yen et al, 1974. ) Neurohormonal control ofgonadotrophin secretion As in most other species, the activity of the gonadotroph in the primate is critically dependent upon hypothalamic gonadotrophin-releasing hormone (Gn-RH).…”