MAINTENANCE OF SPERMIOGENESIS BY EXOGENOUS TESTOSTERONE IN RATS TREATED WITH A GNRH ANTAGONIST - RELATIONSHIP WITH ANDROGEN-BINDING PROTEIN STATUS

The relationship of the testicular distribution and [H-3]dihydrotestosterone-binding capacity of androgen-binding protein (ABP) to the completion of spermiogenesis was examined in mature rats given daily injections of 25 or 250 mug kg-1 body weight of GnRH antagonist (GnRH-A; Ac-D{2}), Nal1, 4Cl-D, Phe2, D-Trp3, D-Arg6, D-Ala10) for two weeks with or without subcutaneous implantation of 10 cm testosterone capsules. GnRH-A administration resulted in a dose-dependent suppression of serum FSH, which was partially prevented in the 250 mug GnRH-A kg-1 group by exogenous testosterone. The total testicular testosterone content and concentration of testosterone in seminiferous tubular fluid were equally suppressed in both groups of rats treated with GnRH-A and receiving the testosterone supplement. ABP concentrations in interstitial and seminiferous tubular fluid were normal in rats given the 25 mug GnRH-A kg-1 dose, and were increased (P < 0.05) by concomitant testosterone treatment. In contrast, ABP concentrations in interstitial and seminiferous tubular fluid were increased in rats given the 250 mug GnRH-A kg-1 dose. This effect was attenuated when exogenous testosterone was given. Although binding of [H-3]dihydrotestosterone by ABP in seminiferous tubular fluid was not affected by GnRH-A treatment, with or without exogenous testosterone, it was reduced in interstitial fluid by GnRH-A in a dose-dependent manner, and partially restored by testosterone administration. While complete spermatogenesis was maintained in rats given 25 mug GnRH-A kg-1, the number of step 7 and step 19 spermatids were both reduced by 35%, and were not affected by testosterone implants. However, administration of 250 mug GnRH-A kg-1 injections resulted in a 60% and 90% reduction of step 7 and step 19 spermatids, respectively. Administration of exogenous testosterone greatly increased the number of step 19 spermatids. This finding was associated with partial normalization of serum FSH, and [H-3]dihydrotestosterone-binding by ABP in interstitial fluid, without changes in testicular testosterone. These results suggest that the bioavailability of ABP within the testis may be critical for the final steps of spermiogenesis.