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Testosterone (T) replacement suppresses the postcastraction hypersection of follicle-stimulating hormone (FSH) in monkeys with an intact central nervous system (CNS), but not in hypothalamic-lesioned animals in which the pituitary-testicular axis is driven by an i.v. infusion of gonadotropin-releasing hormone (GnRH). One possible explanation for this finding is that T replacement markedly reduces the frequency of pulsatile GnRH release in CNS-intact animals. Under such a state of compromised hypophysiotropic drive to the gonadotropes, removal of a specific FSH-inhibiting factor would not be expected to lead to a hypersecretion of FSH. To test this hypothesis indirectly, adult monkeys were orchidectomized and immediately implanted with T-containing Silastic capsules to maintain circulating T concentrations in the upper physiological range, thereby preventing the postcastration hypersecretion of luteinizing hormone (LH) and FSH. An intermittent i.v. infusion of GnRH, identical to that used in studies with the hypothalamic-lesioned, GnRH-replaced model (1 microgram/min for 3 min every 3 h), was initiated 1 wk after castration and T replacement; subsequently, plasma LH and FSH concentrations were determined on Days 8 and 16-18 of GnRH treatment in samples collected every 20 min for 9 h. This GnRH stimulus resulted in a striking elevation in FSH concentrations from 5.2 +/- 1.5 ng/ml (mean +/- SE) before GnRH treatment to 62.6 +/- 20.8 and 118.3 +/- 33.1 ng/ml on Days 8 and 16-18 of GnRH treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In the male rhesus monkey, the negative feedback regulation of gonadotropin secretion by the gonad involves a specific inhibitory action of a testicular hormone on FSH release at the level of the anterior pituitary gland. Neither circulating testosterone (T) nor estradiol appears to be able to account for the testicular inhibition of FSH in this species. The purpose of the present study was to begin to examine the role of gonadal peptides in this regard. To this end, an episodic pattern of activity in the pituitary-Leydig cell axis was restored in seven hypothalamus-lesioned male rhesus monkeys with a chronic and unchanging intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h). This preparation, known as the hypophysiotropic clamp, has been described in detail previously. Charcoal-extracted porcine follicular fluid (pFF) was used as the source of gonadal peptides. In five animals, initiation of combined T replacement and pFF treatment (10-15 ml, sc, every 12 h for 8 days) maintained circulating FSH at concentrations similar to those observed before gonadectomy. Withdrawal of pFF treatment for 8 days while maintaining T replacement resulted in a progressive and dramatic rise in plasma FSH concentrations. Reinitiation of pFF treatment resulted in a return of circulating FSH concentrations toward precastration control values. Changes in LH secretion throughout the experiment were unremarkable. In an attempt to assess any nonspecific effects of porcine protein on gonadotropin secretion, the remaining two animals received charcoal-extracted pig serum instead of pFF. In these animals circulating FSH concentrations rose 7- to 8-fold during the 8 days of combined T replacement and pig serum treatment. These findings provide evidence to support the view that a testicular peptide, most probably inhibin, plays a major role in the negative feedback regulation of gonadotropin secretion in the monkey by exerting an inhibitory action on FSH secretion directly at the level of the anterior pituitary gland.

The purpose of this experiment was to determine whether the testes of the juvenile male rhesus monkey, receiving an invariant intermittent iv infusion of GnRH, produce a specific FSH secretion-inhibiting hormone that exerts its action directly at the level of the pituitary gland. To this end, five male rhesus monkeys between 13-18 months of age were treated with a chronic intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h) for 10 weeks to elicit an adult-like pattern in the episodic activity of the pituitary-Leydig cell axis. Animals were then bilaterally orchidectomized, and on the day of castration testosterone replacement with testosterone-containing Silastic capsules that maintained circulating levels of the steroid at approximately 6 ng/ml was initiated. Sequential blood samples were collected before castration and at 4-5, 11-13, and 18-19 days thereafter. Removal of the testes resulted in a marked and selective hypersecretion of FSH, a response very similar to that observed previously in hypothalamus-lesioned GnRH-treated adult males. This finding indicates that it will be possible to substitute the juvenile male for the much larger hypothalamus-lesioned adult in future studies requiring a hypophysiotropic clamp preparation. Such a modification of this experimental model will facilitate an examination of the effects on FSH secretion of passive immunization with inhibin antisera and of administering pure inhibin peptides.