ABSTRACT

The present study was designed to investigate the relative contributions of FSH and testosterone in the initiation of testicular growth and function in primates. Four groups (n = 4/group) of juvenile rhesus monkeys (Macaca mulatta), 12–18 months old, were treated with vehicle, a highly purified human FSH preparation (hFSH; Fertinorm, 3 IU/kg per day), testosterone (testosterone enanthate, 125 mg/week) or FSH plus testosterone, for a period of 12 weeks. Compared with vehicle treatment, the administration of hormones significantly (P <0·05) increased testicular weight and volume, and the diameter of seminiferous tubules. The number of Sertoli cells per tubule cross-section also increased significantly (P <0·05). Numbers of Ad (dark) spermatogonia (reserve stem cells) were not significantly influenced by any treatment. In contrast, the numbers of Ap (pale) spermatogonia (renewing stem cells) were significantly (P <0·05) stimulated with hFSH and testosterone alone. Following the combined treatment, numbers of Ap spermatogonia were also higher compared with control but this effect did not attain statistical significance. In half of the animals in both testosterone-treated groups, a few prophase I spermatocytes were present. Inhibin concentrations reached adult levels in hFSH-treated groups but remained unaffected by testosterone. Conversely, testosterone failed to influence inhibin levels and, unlike hFSH, increased testicular androgen concentration and epididymal weights. Our observations suggest that hFSH and testosterone alone are capable of initiating testicular growth and gametogenesis in an immature primate. Both hormones probably act via activation of the proliferation of Ap spermatogonia, which are considered to be renewing stem cells within the testis. This study also suggests that androgens might be involved in the morphological differentiation of the immature primate Sertoli cell, whereas the secretory activity of the seminiferous tubule, in terms of peripheral inhibin levels, might be under the influence of FSH.

Journal of Endocrinology (1993) 136, 235–243

We investigated a possible modulation of growth hormone (GH) secretion by testosterone by measuring the growth hormone releasing hormone (GHRH)-stimulated and N-methyl-d,l-aspartic acid (NMA)-induced GH secretion in adult rhesus monkeys. Intact, orchidectomized and testosterone-substituted (testosterone enanthate 125 mg/week, i.m. for 5 weeks) orchidectomized monkeys (n=5) were used in the study. GHRH (25 microg/kg body weight) or NMA (15 mg/kg body weight) was infused through a Teflon cannula implanted in the saphenous vein. Sequential blood samples were collected 30-60 min before and 60 min after the injection of the neurohormone or the drug at 10-20-min intervals. All bleedings were carried out under ketamine hydrochloride anaesthesia (initial dose 5 mg/kg body weight i.m., followed by 2.5 mg/kg at 30-min intervals). The plasma concentrations of GH, testosterone and oestradiol (E(2)) were determined by using specific assay systems. Administration of GHRH elicited a significant increase in GH secretion in all three groups of animals. There was no significant difference in the responsiveness of pituitary somatotrophs to exogenous GHRH challenges between intact and orchidectomized monkeys and testosterone replacement in orchidectomized animals did not significantly alter the GHRH-induced GH response. The responsiveness of hypothalamic GHRH neurones apparently did undergo a qualitative change after orchidectomy, as GH response to NMA was less in orchidectomized animals than in intact monkeys. The responsiveness of GHRH neurones to exogenous NMA was restored and even potentiated when orchidectomized monkeys were treated with testosterone. Taken together, these findings suggest that testosterone does not affect the sensitivity of the pituitary somatotrophs to GHRH but stimulates the secretion of GH by modulation of the NMDA drive to GHRH neurones.

Although the gonadotropic control of the spermatogenic process is well established, the endocrine regulation of the timing and kinetics of germ cell development has received little attention. We found previously that the administration of a GnRH antagonist (ANT) over a period of 25 days could retard spermatid development and slightly prolong cycle length in intact adult cynomolgus monkeys (Macaca fascicularis). The aim of the present study was to investigate the effects of extended exposure to ANT on the duration of the cycle of the seminiferous epithelium in the monkey. Additionally, the duration of spermatogenesis was studied in the ANT-exposed rat model. In experiment 1, monkeys were given either saline or ANT (n=6/group) and on day 30 all animals received a single injection of 5-bromodeoxyuridine (BrdU) to label S-phase germ cells. Testicular biopsies were taken on days 39, 43, 47 and 51 (end of treatment) for BrdU localization and flow cytometric analysis. ANT treatment suppressed hormone levels, reduced testis size by >70% and severely impaired germ cell production. Despite these alterations, cycle duration remained unchanged at all time-points compared with controls (10.12+/-0.15 days vs 10.16+/- 0.44 days). In experiment 2, adult male Sprague-Dawley rats (n=15/group) received either vehicle (VEH) or ANT for 14 days and received BrdU injection on day 2. Cycle duration was found to be shorter in the ANT-treated group (12.45+/-0.09 days) than in the control group (12.75+/-0.08, P<0.05). As spermatogenic cycle length in this control group was longer than that of our historical controls (range: 12.37-12.53 days), experiment 2 was repeated (n=10/group). In experiment 3, cycle duration was 12.51+/-0.02 for VEH and 12.46+/-0.05 for the ANT-treated group (P>0.05) in both species. We concluded that the duration of the cycle of the seminiferous epithelium in monkeys and rats is independent of gonadotropins but is rather regulated by the spermatogenic tissue itself.