Δ4-5α-Hydrogenase in Immature Rat Testes: Its Intracellular Distribution, Enzyme Kinetics, and Influence of Administered Gonadotrophin and Testosterone Propionate

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Abstract
From the incubation study of androstenedione-4-14C with subcellular fractions of immature rat testes in the presence of NADPH, it was concluded that Δ4-5α-hydrogenase which converted the substrate to 5α-androstanedione was localized in the microsomal fraction (10,000-105,000 ×g precipitate), while 3α-hydroxysteroid dehydrogenase was localized in the supernatant fluid at 105,000 ×g. The Km value of the microsomal Δ4-5α-hydrogenase for androstenedione was estimated as 8.7 × 10−5m. Human chorionic gonadotrophin (30 IU) and/or testosterone propionate (100 μg) were administered daily for 1 and 2 weeks to the immature rats at the 28th day after birth. When the enzymic activities related to testicular transformation of steroids were examined in the cell-free homogenates and in the microsomal fractions, Δ4-5α-hydrogenation of androstenedione and 17α-hydroxyprogesterone and also the side-chain cleavage of 17α-hydroxyprogesterone were severely inhibited by the treatment with testosterone propionate alone. After the administration of human chorionic gonadotrophin alone, androstenedione-Δ4-5α-hydrogenase activity was not significantly changed, but production of 5α-saturated C21-steroids from 17α-hydroxyprogesterone was inhibited, and androgen production from the 17α-hydroxyprogesterone was strongly enhanced. Suppression of the Δ4-5α-hydrogenation of androstenedione and of 17α-hydroxyprogesterone and the side-chain cleavage of 17α-hydroxyprogesterone by testosterone propionate administration were compensated by the simultaneous administration of the gonadotrophin with testosterone propionate. Particularly, the administration of human chorionic gonadotrophin with testosterone propionate for 2 weeks increased the production of Δ4-3-oxo-C19-steroids from 17α-hydroxyprogesterone beyond the control level. From the results obtained, the fate and role of Δ4-5α-hydrogenase were discussed in relation to androgen production in the course of maturation from the immature stage. (Endocrinology86: 1215, 1970)

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