Dynamics of the follicle-stimulating hormone (FSH)-inhibin B feedback loopand its role in regulating spermatogenesis in the adult male rhesus monkey(Macaca mulatta) as revealed by unilateral orchidectomy

The purpose of this study was to document the morphological changes in the seminiferous epithelium that underlie the compensatory testicular hypertrop hy observed in response to unilateral orchidectomy (UO) in the adult rhesus monkey and to describe the concomitant response in the endocrine feedback loops controlling testicular function in this species. Adult male monkeys w ere implanted with indwelling venous catheters; seven animals were then sub jected to UO (data are presented from six) and three to sham UO. Profiles o f circulating concentrations of FSH, LH, testosterone (T), inhibin B, and p ro-alpha-C were monitored in 12-h series of sequential blood samples collec ted before, on the day of UO (day 0), and on days 1, 2, 4, 8, 16, 32, and 4 2 or 43 after UO. In the UO monkeys, the remaining testis was taken on day 44. Sertoli and germ cells in the removed and remaining testes were counted and expressed either as number per testis or, in the case of the different iated spermatogonia (B-1, B-2, B-3, and B-4), as number per cross-section o f the seminiferous tubule. UO was associated with a marked increase in the number of all germ cells mo re mature than undifferentiated spermatogonia (Ap) in the remaining testis. Sertoli cell number, on the other hand, did not change, and it is therefor e reasonable to propose that the primary locus of the spermatogenic compens ation was the differentiated spermatogonia. The additional finding that the relationship between the number of Sertoli cells and total germ cells in t he remaining testis became robust (r = 0.92; P < 0.01 vss, r = 0.44; P > 0. 05 for the removed testis) indicated that in the monkey, spermatogenesis do es not normally operate at its ceiling. The increased drive to the seminife rous tubule of the remaining testis is hypothesized to be mediated by the s ustained increase in FSH secretion that was observed after UO, although a r ole for increased testicular T production cannot be excluded. The stimulus for increased FSH secretion was presumably provided by the abrupt, 50% decl ine in circulating inhibin B levels. Interestingly, inhibin B secretion by the remaining testis was not dramatically affected by UO, and therefore, th e deficit in circulating levels of this hormone and thus the error signal t o FSH secretion were maintained for the duration of the experiment. In cont rast, the changes in circulating LH and T concentrations were only transien t, and within 48 h of UO, these hormonal parameters had returned to control values. The mechanisms by which the remaining testis rapidly acquires the capacity to double T production in the face of an unchanging LH drive remai ns to be determined. The foregoing body of evidence suggests that sperm output by the monkey tes tis is regulated by the circulating concentration of FSH and that in physio logical situations, FSH secretion is insufficient to stimulate spermatogene sis to its ceiling. The results also indicate that FSH secretion is control led by a feedback system in which the feedforward arm (FSH-inhibin B) is le ss robust than the feedback loop (inhibin B-FSH). Thus, a decrease in the i nhibin B feedback signal results in a sustained increase in FSH secretion t hat drives the testes toward their spermatogenic ceiling, which is presumab ly set by Sertoli cell number.