ANDROGEN ACTION ON THE RESTORATION OF SPERMATOGENESIS IN ADULT RATS -EFFECTS OF HUMAN CHORIONIC-GONADOTROPIN, TESTOSTERONE AND FLUTAMIDE ADMINISTRATION ON GERM-CELL NUMBER

Spermatogonial proliferation is a critical but poorly understood deter minant of the spermatogenic process. In rats, exogenous testosterone p lus oestradiol (TE) markedly suppresses serum LH and testicular testos terone levels. In the TE-treated rat, spermatogonial number declines t o approximate to 65% of control levels while round to elongated sperma tid maturation is interrupted. The partial restoration of testicular t estosterone levels by exogenous testosterone administration restores s permatid maturation but neither testicular weight nor spermatogonial n umber are normalized. This study aimed to determine the role of testos terone and/or non-androgenic Leydig cell factors in the restoration of spermatogonial number in the testosterone-treated rat. Germ cell numb ers were assessed using stereological methods and expressed as germ ce ll number per testis. Adult Sprague Dawley rats initially received 3 c m testosterone plus 0.4 cm oestradiol Silastic implants for 9 weeks to suppress spermatogenesis, followed by 10 days of either (i) exogenous testosterone using implants (T24 cm) or testosterone esters (5 or 25 mg sc every third day), or (ii) human chorionic gonadotrophin (hCG; 0. 5, 1.25, 2.5 or 10 IU/kg sc daily) as an LH substitute to restore Leyd ig cell function. Following TE treatment, testicular weights and testi cular testosterone levels were reduced to 31% and 1.3% of control leve ls, respectively. In response to exogenous testosterone administration , testicular weight was restored to 52-58% of controls while testicula r testosterone levels increased to only 3.5-17.3% of controls despite serum testosterone levels 4.5-24-fold above control. In response to hC G-treatments, a graded increase in testicular testosterone levels was achieved (2.6-205% of control) and testicular weights increased to 35- 56% of control. TE suppression reduced (p < 0.05) type A spermatogonia and type B spermatogonia/preleptotene spermatocyte numbers per testis to 61% and 77% of control, respectively; however, neither subsequent testosterone nor hCG treatments significantly increased either germ ce ll number. In a second study, hCG (1.25 IU/hg) was administered alone or in combination with the androgen receptor antagonist, flutamide (10 0 mg/kg sc daily), to withdraw androgenic effects at all sta ses of sp ermatogenesis. The TE-induced suppression of type A spermatogonia (59% control) and type B spermatogonia/preleptotene spermatocytes (68% con trol) was not affected by hCG +/- flutamide. On the other hand, as exp ected, hCG increased the number of elongated spermatids (p < 0.05). Th e co-administration of flutamide reduced (p < 0.05) the numbers of all pachytene spermatocyte forms, round and elongated spermatids below th ose of TE-treated animals. We conclude that neither exogenous testoste rone nor hCG is capable of restoring spermatogonial number in the TE-t reated rat within 10 days despite the partial or full restoration of t esticular testosterone levels. No evidence was found for the involveme nt of non-androgenic Leydig factors in the control of spermatogonial n umbers. The data from flutamide-treated animals demonstrates that resi dual androgen effects are present in the TE model as, even in the pres ence of testicular testosterone levels below that needed for spermatid apparent.