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  • Title: In vitro steroid metabolic studies in human testes I: Effects of estrogen on progesterone metabolism.
    Author: Rodriguez-Rigau LJ, Tcholakian RK, Smith KD, Steinberger E.
    Journal: Steroids; 1977 Jun; 29(6):771-86. PubMed ID: 910250.
    Abstract:
    A technique of incubation of testicular tissue in vitro with radiolabeled precursors was applied in the investigation of the steroid biosynthesis by testes of four young men after long-term, high-dose estrogen treatment. A positive correlation between plasma and testicular steroid levels, and in vitro capacity of the testes to metabolize progesterone was demonstrated. Estrogen administration produced a very significant inhibition of plasma and testicular levels of testosterone. The in vitro synthesis of testosterone from progesterone was very severely impaired; especially 17alpha-hydroxylation of progesterone. 20alpha-hydroxysteroid-dehydrogenase activity was found to be increased after estrogen treatment, both in vivo and in vitro. These findings suggest that testicular 17alpha-hydroxylase activity (and possibly also 17-20 lyase activity) is either under gonadotropin regulation, or is directly suppressed by estrogen. This could result by decreased enzyme synthesis, direct enzyme inhibition or affectation of the cofactors or cytochromes necessary for the enzymatic activity. 20alpha-reduction of C21-steroids would represent an alternative pathway for their catabolism, not regulated by gonadotropin or not affected by estrogen, that would be significant in situations with reduced 17alpha-hydroxylase activity. 4 male transsexuals, aged 23-46 years, were treated with ethinyl estradiol (1-2 mg daily) for at least 12 months prior to orchiectomy and sex-change surgery. The pattern of in vitro steroid biosynthesis by testicular tissue before and after this therapy was examined histologically and hormonally. Serum follicle stimulating hormone and luteinizing hormone were measured by radioimmunoassay as were plasma and testicular concentrations of testosterone (T). Plasma estradiol (E) and testicular progesterone (P) were also measured. In vitro steroid biosynthetic studies were made with radiolabeled precursors. Histology showed a uniform picture of spermatogenic arrest at the primary spermatocyte level after treatment. Concentrations of T, P, E, and 20alpha-dihydroxyprogesterone in the testes of the treated men showed that all hormones except E decreased markedly. Biosynthesis studies demonstrate that radioactive P substrate was poorly metabolized. In vitro synthesis of T from P was severely impaired; 17alpha-hydroxylation decreased substantially while 20alpha-hydroxy-steroid-dehydrogenase activity increased after estrogen treatment. It is suggested that 17alpha-hydroxylase activity is either under gonadotropin regulation or is directly inhibited by estrogen treatment. The increase in 20alpha-reduction might represent an alternate pathway unaffected by the treatment.
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