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.

In rhesus monkeys with hypothalamic lesions (which appear to abolish the endogenous production of gonadotropin-releasing hormone), normal ovulatory mestrual cycles were reestablished by an unvarying, long-term replacement regimen consisting of one intravenous pulse of synthetic gonadotropic-releasing hormone per hour. This finding is in accord with the hypothesis that the pattern of pituitary gonadotropin secretion throughout the menstrual cycle (basal secretion interrupted, once every 28 days on the average, by a preovulatory surge) is not directed by alterations in hypothalamic gonadotropin-releasing hormone secretion but by the ebb and flow of ovarian estrogens acting directly on the pituitary gland.

No abstract

The site and mode of the feedback actions of testicular hormones on gonadotropin secretion in the adult rhesus monkey were investigated using the arcuate-lesioned preparation previously employed by others to study cognate problems in the female. The negative feedback loop that governs LH and FSH release in the male monkey was opened without changing either the frequency or amplitude of intermittent GnRH stimulation of the pituitary gonadotrophs, which was clamped by exogenous GnRH replacement at a level that approximated the intact or closed loop hypophysiotropic signal. In this manner, the relative importance of adenohypophysial vs. hypothalamic sites of feedback action of testicular hormones on LH and FSH secretion was assessed. To accomplish the foregoing, radiofrequency lesions were placed in the region of the arcuate nucleus to abolish endogenous hypothalamic GnRH secretion. Patterns of temporally coupled episodes of pituitary LH and testicular testosterone discharge that in nonlesioned animals characteristically occur, on the average, once every 3 h throughout the 24-h light-dark cycle were restored in lesioned animals by an intermittent iv infusion of GnRH (0.1 micrograms/min for 3 min every 3 h). Bilateral orchidectomy in this experimental paradigm elicited only small increments in LH pulse amplitude and mean plasma LH concentration, a response in striking contrast to the dramatic postcastration LH hypersecretion observed in animals with intact hypothalami that respond to the opening of the negative feedback loop with an apparent acceleration in the endogenous frequency of intermittent GnRH secretion. A marked rise in mean plasma LH concentration in arcuate-lesioned males, however, was forth-coming when the frequency of intermittent exogenous GnRH stimulation was increased 2-3 weeks after castration from one pulse every 3 h (intact frequency) to one pulse per h (castrate frequency). These findings fail to provide evidence for a major inhibitory feedback action of the testes on LH secretion at the level of the adenohypophysis. They are entirely consistent, however, with the hypothesis that the negative feedback control of LH release by the male gonad is mediated, principally, via the central nervous system by an action of testicular hormone, most probably testosterone, to retard the frequency of the neural timing mechanism that governs the intermittent pattern of GnRH release by the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

SUMMARY The assays of testosterone and corticosteroids in plasma from adult male rhesus monkeys using competitive protein-binding and radioimmunoassay techniques are described. The radioimmunoassay for testosterone was conducted without chromatography and, therefore, additionally estimated 17β-hydroxy-5α-androstan-3-one (dihydrotestosterone). Levels of testosterone in the peripheral plasma of 14 intact male rhesus monkeys showed marked fluctuations over a period of 24 h. Concentrations of testosterone at 22.00 h (1776 ± 814 ( ± s.d.) ng/100 ml) were approximately double those at 08.00 h (858 ± 407 ng/100 ml), 12.00 h (898 ± 316 ng/100 ml) and 16.00 h (784 ± 530 ng/100 ml). Castration resulted in low plasma testosterone levels (85 ± 29 ng/100 ml), and the increases at 22.00 h were no longer observed. In intact males, the 'basal' plasma corticosteroidlevel(08.00 h) was 22·4 ± 6·0 μg/100 ml. Administration of synthetic corticotrophin raised plasma corticosteroid levels without changing plasma testosterone concentration. Because plasma testosterone levels were not related to changes in adrenocortical activity, the noctural rises appear to be due to changes in testicular secretion.