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5 alpha-reductase activity in human fetal testis

R Azoury, F Eyal, C Springer

    The International Journal of Biochemistry
    |January 1, 1982
    PubMed
    Summary

    Human fetal testes convert pregnenolone primarily to androstenediol and androstenedione, with minimal 5 alpha-reduction. However, preincubation revealed significant 5 alpha-reductase activity, producing dihydrotestosterone (DHT).

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    Area of Science:

    • Endocrinology
    • Steroid Metabolism
    • Developmental Biology

    Background:

    • The human fetal testis plays a crucial role in androgen biosynthesis during development.
    • Understanding steroidogenic enzyme activity in the fetal testis is essential for comprehending male reproductive development.

    Purpose of the Study:

    • To investigate the steroidogenic capabilities of human fetal testes, specifically focusing on pregnenolone and progesterone metabolism.
    • To characterize the activity and kinetics of 5 alpha-reductase in human fetal testicular homogenates.

    Main Methods:

    • Incubation of human fetal testis (32-weeks-old) homogenates with radiolabeled pregnenolone and progesterone.
    • Separation and identification of radioactive metabolites using chromatography, derivative formation, and recrystallization.
    • Enzyme activity assays for 5 alpha-reductase, including kinetic analysis (Michaelis-Menten).

    Main Results:

    • Human fetal testes converted approximately 30% of [3H]pregnenolone mainly to [3H]androst-5-ene-3 alpha, 17 beta-diol and [3H]-3 beta-hydroxyandrost-5-ene-17-one.
    • Minimal 5 alpha-reduced steroids were detected from direct incubation.
    • Preincubation of the 10,000 g supernatant, particularly with 3-hydroxysteroid dehydrogenase preparation, led to the identification of dihydrotestosterone (DHT) and demonstrated significant 5 alpha-reductase activity following Michaelis-Menten kinetics.

    Conclusions:

    • Human fetal testes exhibit limited direct 5 alpha-reductase activity on pregnenolone.
    • The presence of latent 5 alpha-reductase activity, inducible by preincubation, suggests developmental regulation of this pathway.
    • This latent activity is capable of producing DHT, a potent androgen, indicating potential for its synthesis in the fetal testis under specific conditions.

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