Evidence from the Rhesus Monkey (Macaco, mulatto) for the View that Negative Feedback Control of Luteinizing Hormone Secretion by the Testis Is Mediated by a Deceleration of Hypothalamic Gonadotropin-Releasing Hormone Pulse Frequency*

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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 [luteinizing hormone] and FSH release in the male monkey was opened without changing either the frequency or amplitude of intermittent GnRH [gonadotropin releasing hormone] 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 i.v. infusion of GnRH (0.1 .mu.g/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 was forthcoming when the frequency of intermittent exogenous GnRH stimulation was increased 2-3 wk after castration from one pulse every 3 h (intact frequency) to 1 pulse/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 with the hypothesis that the negative feedback control of LH release by the male gonad is mediated, principally, via the CNS 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. Plasma concentrations of FSH, in contrast to those of LH, exhibited a rapid and dramatic elevation after castration in arcuate lesioned animals, in which the hypophysiotropic stimulation of the gonadotrophs after gonadectomy was clamped at a frequency normally associated with the intact situation (1 pulse every 3 h). In this species the testicular regulation of gonadotropin secretion apparently includes an additional component that involves a specific inhibitory action of testicular hormone on FSH release at the level of the anterior pituitary gland.