Lack of Metabolism of Progesterone, Testosterone and Pregnenolone to 5α-Products in Monkey and Human estes Compared with Rodent Testes1

Abstract

Testicular homogenates from rhesus monkeys 1.0, 2.0, 2.5, 2.7, 2.8, 3.0, 7, 8, 8.5 and 9 years of age and those from 33- and 100-day-old rats were incubated with ³H-progesterone, ³H-testosterone and ¹⁴C-pregnenolone in the presence of co-factors. In addition, homogenates of testes obtained from patients 3, 4, 5, 7, 15 and 83 years of age at the time of orehiectomy were incubated with ³H-progesterone and ¹⁴C-pregnenolone. After incubation, radioactive products were separated and identified by column and paper chromatography with derivative formation and recrystallization to constant specific activity. Testes from monkeys and humans of different ages converted significant amounts (up to 70%) of progesterone and pregnenolone to 17α-hydroxyprogesterone, androstenedione, testosterone, 20α-hydroxypregn- 4-en-3-one and/or 16α-hydroxyprogesterone. Testes of monkeys 1.0–9 years of age converted 1–30% of testosterone to androstenedione. However, no or very small amounts (less than 0.4% of each product) of 5α-reduced metabolites of Δ4–3-ketosteroids were shown to be formed in all monkey and human testes examined. On the other hand, in prepubertal rat testes under the same incubation conditions, conversion of progesterone and testosterone to 5α-reduced steroids such as 3α17α-dihydroxy-5α-pregnan-20-one, androsterone and 5α-androstane-3α, 17β-diol reached 70%. In contrast to rodents, the immature testes of monkeys and humans do not form large amounts of 5α-reduced C₁₉-steroids. This might reflect a different mechanism controlling testosterone accumulation in the prepubertal testes of monkey and human.