In the Rhesus Monkey (Macaca mulatto), the Negative Feedback Regulation of Follicle-Stimulating Hormone Secretion by an Action of Testicular Hormone Directly at the Level of the Anterior Pituitary Gland Cannot be Accounted for by Either Testosterone or Estradiol*

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Abstract
In the male rhesus monkey, the negative feedback regulation of gonadotropin secretion by the gonad appears to involve a specific inhibitory action of testicular hormone on FSH release at the level of the anterior pituitary gland. The purpose of the present study, which used the hypophysiotropic clamp preparation, was to determine whether circulating testosterone (T) or estradiol (E) comprises a major component of the testicular FSH-inhibiting factor in this species. Endogenous hypothalamic GnRH secretion was abolished or severely compromised in five adult male rhesus monkeys by placement of radiofrequency lesions in the region of the arcuate nucleus. Subsequently, an episodic pattern of activity in the pituitary-Leydig cell axis of these animals was restored by a chronic and unchanging intermittent iv infusion of GnRH (0.1 .mu.g/min for 3 min ever 3 h), which appears to provide the gonadotropes of lesioned animals with a hypophysiotropic drive comparable to that produced by the hypothalamus of animals with an intact central nervous system. Treatment of three animals with a specific anti-E-.gamma.-globulin fraction resulted in a marked and sustained rise in E-binding activity in serum, but this neutralization of circulating E did not elicit hypersecretion of FSH. In all five animals, initiation of T replacement on the day of orchidectomy, which maintained circulating T concentrations in the high testis-intact control range, failed to prevent the postcastration hypersecretion of FSH that is evoked after removal of testis in the hypophysiotropic clamp preparation. As expected, the changes in circulating LH levels during immunoneutralization and after orchidectomy and T replacement were unremarkable. These findings indicate that neither circulating T nor E can account for the testicular inhibition of FSH secretion in the rhesus monkey and thus lead, by a process of exclusion, to the view that in this species the negative feedback regulation of FSH release by the testis is mediated directly at the level of the gonadotrope by an inhibitory action of a nonsteroidal hormone, most probably the recently identified gonadal peptide inhibin.

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