Publisher Summary
This chapter discusses the construction of a model of the neuroendocrine control system that governs the 28-day ovarian cycle of the rhesus monkey. This model has three basic components: the arcuate nucleus of the hypothalamus, the gonadotrophs of the pituitary gland, and the ovary. The arcuate nucleus is the central component of the control system. The gonadotrophs respond to this unvarying pulsatile gonadotropin releasing hormone (GnRH) stimulation by releasing pulses of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Immature follicles respond to this unvarying gonadotropic stimulus by increasing in size and secreting increasing quantities of estradiol, which achieve maxima near mid-cycle. This process occupies approximately 14 days. The magnitude of the response to each GnRH pulse is modulated by estradiol acting directly on the gonadotrophs. The characteristic duration of the rhesus monkey ovarian cycle is thus determined by the duration of follicular development. This can occur in the presence of an absolutely unvarying pattern of hypophysiotropic stimulation.

The neuroendocrine control of the menstrual cycle.

In rhesus monkeys with hypothalamic lesions that abolish gonadotropic hormone release by the pituitary gland, the constant infusion of exogenous gonadotropin-releasing hormone (GnRH) fails to restore sustained gonadotropin secretion. In marked contrast, intermittent administration of the synthetic decapeptide once per hour, the physiological frequency of gonadotropin release in the monkeys, reestablishes pituitary gonadotropin secretion. This phenomenon is attributable to the pattern of GnRH delivery rather than to the amounts of this hormone to which the cells of the pituitary are exposed. Moreover, the initiation of continuous GnRH administration in animals with lesions and in which gonadotropin secretion is reestablished by intermittent GnRH replacement can result in a "desensitization" or "down regulation" of the processes responsible for gonadotropin release.

https://science.sciencemag.org/content/sci/202/4368/631.full.pdf

Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone

In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"

Studying sex and gender differences in pain and analgesia: a consensus report

Electrophysiology of hypothalamic magnocellular neurones secreting oxytocin and vasopressin

Consensus report Studying sex and gender differences in pain and analgesia: A consensus report

Blood samples were withdrawn at 10-, 20- or 30-min intervals for 6–12 hr from 13 ovariectomized and 7 intact female rhesus monkeys bearing indwelling cardiac catheters and restrained in primate chairs. Plasma LH and GH concentrations were determined by radioimmunoassay. Twenty-four experiments in ovariectomized animals revealed a striking rhythmic pattern in plasma LH levels having a period of approximately 1 hr, which was asynchronous with variations in plasma GH concentrations when these occurred. The LH oscillations, which had an excursion of 40–92 % of the mean hormone concentration, occurred with a mean period of 75 min and a mode of 60 min. In a typical rhythmic sequence, LH levels increased from nadir to peak during one 10-min sampling interval and decayed exponentially for the next 60 min. The t½ calculated from 19 such decay curves based on 10-min sampling intervals was 72 min, which is similar to the estimated t½ of exogenous LH in intact females. Moreover, there was a significant positive corre...

Circhoral Oscillations of Plasma LH Levels in the Ovariectomized Rhesus Monkey

Subcutaneous injections of estradiol benzoate in oil, resulting in a sustained elevation of circulating estrogen levels, induced LH discharges markedly similar to the spontaneous preovulatory LH surges observed during the normal menstrual cycle. Exogenous estrogen leading to high plasma estrogen concentrations for brief periods (less than 12 hr) was ineffective in this regard. The discharge of LH in response to estrogen administration was observed in cycling and in ovariectomized females but not in intact males or in lactating females. It is concluded that the “trigger” for LH discharge, in the rhesus monkey, consists of an effective increment in circulating estrogen levels which must be maintained for at least 12 hr and that this positive feedback action of the steroid is clearly operative only in nonlactating adult females. (Endocrinology 89: 1034, 1971)

Estrogen induction of LH release in the Rhesus monkey.

In ovariectomized rhesus monkeys, single injections into the right atrium of the neuroleptic drugs chlorpromazine and haloperidol or of the α-adrenergic blockers phentolamine and phenoxybenzamine were followed, within min, by an interruption in the circhoral pulsatile discharge of LH and a resultant fall in the plasma concentration of the hormone. This inhibition of LH secretion was usually sustained for some hr and was terminated by an abrupt resumption of the pulsatile secretory pattern. These responses were qualitatively indistinguishable from those previously reported to follow single injections of estradiol. In contrast, the p-adrenergic blocking agent propanolol or pentobarbital in anesthetic doses had no, or equivocal effects on the pulsatile pattern of LH discharge. Evidence is adduced in support of the view that these discharges of LH, as observed in ovariectomized monkeys, are the consequence of intermittant dopaminergic and/or nor-adrenergic signals to the LRF secreting cells of the hypothalamu...

The Pharmacologic Blockade of the Circhoral Mode of LH Secretion in the Ovariectomized Rhesus Monkey

The pulsatile, circhoral discharges of LH observed in ovariectomized rhesus monkeys were blocked within min following single intravenous injections of 17β-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 th...

The negative feedback control by estradiol and progesterone of LH secretion in the ovariectomized rhesus monkey.

The changes in plasma LH concentrations, as measured by a specific radioimmunoassay, were observed in 9 female and 3 male rhesus monkeys for a period of 20–35 days after gonadectomy. A 10-fold increase in plasma LH levels occurred during the first 3 weeks following castration. Hourly blood samples obtained from each of 3 chronically ovariectomized monkeys during a 24-hr period revealed major, seemingly random, peaks in plasma LH concentrations. (Endocrinology 87: 847, 1970)

A.N. Bhattacharya

Papers

Circhoral Oscillations of Plasma LH Levels in the Ovariectomized Rhesus Monkey

Estrogen induction of LH release in the Rhesus monkey.

The Pharmacologic Blockade of the Circhoral Mode of LH Secretion in the Ovariectomized Rhesus Monkey

The negative feedback control by estradiol and progesterone of LH secretion in the ovariectomized rhesus monkey.

Effects of gonadectomy on plasma LH concentration in the rhesus monkey.