Spermatogenesis without gonadotropins: Maintenance has a lower testosterone threshold than initiation

We showed previously that testosterone (T) alone could induce spermatogenes is and produce normally fertile spermatozoa in the absence of circulating g onadotropins. These studies used the hpg mouse, which is characterized by a congenital gonadotrophin deficiency due to a major deletion in the GnRH ge ne. Administering T by a subdermal implant of a SILASTIC brand tube impregn ated with crystalline T showed that the androgenic requirement for full ind uction of spermatogenesis was a 1-cm length implant. Using this unique mode l of spermatogenesis without gonadotropins, we have now investigated the qu antitative requirement for androgens to maintain spermatogenesis by testing the hypothesis that the androgenic threshold required for induction and ma intenance of spermatogenesis are the same. Spermatogenesis was induced in h omozygous hpg mice by T administration for 6 weeks. The first experiment de termined the time-course of the regression of spermatogenesis after removal of the T-impregnated SILASTIC brand implant. Elongated spermatids were abs ent by 3 weeks and testicular weight regression was maximal by 4 weeks afte r androgen withdrawal. The second experiment examined the effects on mainte nance of spermatogenesis of reducing the T dose. After full induction of sp ermatogenesis in homozygous hpg mice, the T implants mere replaced with a r ange of smaller size T-impregnated SILASTIC brand implants for a further 4 weeks. All androgen-sensitive end-points (testis weight, tubular, and lumin al diameters, round spermatids) were fully maintained with T implants of 0. 06 cm and elongated spermatids with T implants of 0.25 cm. A further experi ment showed that at very low T doses (0.06, 0.125 cm) the T effects observe d at 4 weeks were maintained at 6 and 11 weeks duration. We conclude that t he androgenic threshold to maintain spermatogenesis in the mouse is an orde r of magnitude lower than the threshold required for inducing spermatogenes is. This distinction suggests that the mechanism of action of testosterone in inducing spermatogenesis may involve regulation of a genetic switch to c omplete meiosis, whereas the maintenance involves a different locus of acti on. These findings suggest that further studies of androgen-dependent meiot ic genes maybe central to understanding the regulation and molecular basis of androgen-driven induction and maintenance of spermatogenesis.