Hypophysectomy and simultaneous testosterone replacement: Effects on male rat reproductive tract arid epididymal Δ⁴-5α-reductase and 3α-hydroxysteroid dehydrogenase

Rat epididymal ΔA⁴-5α-reductase and 3α-hydroxysteroid dehydrogenase activities are differentially controlled. We have shown previously that 3α-hydroxysteroid dehydrogenase activity can be regulated by circulating testosterone, whereas Δ⁴-5α-reductase activity is at least partially dependent on direct testicular secretions. The present experiment was designed to determine if a certain testicular cell type(s) (Leydig cells, condensed spermat id, or spermatozoa) is responsible for elaborating this required substance. A hypophysectomy-testosterone replacement model was used. Adult male Sprague-Dawley rats were either left intact as controls (Co) or were hypophysectomized and simultaneously treated with subcutaneous polydimethylsiloxane implants, which were empty capsules (HP-O) or testosterone-filled capsules measuring 1.0 cm (HP-1), 2.4 cm (HP-2), or 22.0 cm (HP-3). The animals were decapitated 4 weeks later. The weights of the sex accessory tissues (ventral prostate and seminal vesicles) and the serum testosterone concentrations were diminished in the HP-0 and HP-1 groups compared to those in the Co group, were indistinguishable between the Co and HP-2 groups, and were markedly elevated in the HP- 3 group. The epididymal content of spermatozoa was reduced to undetectable levels in the HP-0 and HP-1 groups, to less than 10% of Co in the HP-2 groups, and maintained at Co levels in the HP-3 group. Similar observations were made for the testicular sperm content. Epididymal Δ⁴-5α-reductase activity decreased from 25.1± 2.4 nmol dihydrotestosterone formed/tissue · h in the Co group to 1.0 ± 0.2 in the HP-0 group; depending on the testosterone dose used, this decrease could be partially or completely averted.Δ⁴-5α-Reductase activities of 6.3 ± 0.6, 15.5 ± 2.1, and 27.2± 4.1 nmol dihydrotestosterone formed/tissueh were found in the HP-1, HP-2, and HP-3 groups, respectively. Epididymal 3α-hydroxysteroid dehydrogenase activity did not differ significantly from Co in the HP-2 and HP-3 groups; a marked diminution was noted in the HP-0 and HP-1 groups, the only two groups where serum androgen was below that of Co. These results indicate that epididymal Δ⁴-5α-reductase activity is not directly controlled by the presence of spermatozoa in the epididymis, by testicular spermatids and spermatozoa, or by gonadotropin-mediated Leydig cell secretions. Rather, they suggest that this enzymatic activity is dependent, at least in part, on a factor from the testis which is itself under androgen control and is probably of Sertoli cell origin.