Effect of Long Term Treatment with Gonadotrophic Hormones on In Vitro Metabolism of [3H]Progesterone in Human Testicular Tissue

Gonadotrophic hormones appear to influence the preferred pathways for intratesticular androgen biosynthesis. Individuals with low levels of gonadotrophin in the peripheral circulation, as e. g. prepubertal boys and a hypophysectomized adult male, have previously been shown to metabolize [³H]progesterone in vitro mainly to 20α-dihydroprogesterone (20α-DH-P) and less to 17α-hydroxyprogesterone (17α-OH-P), i. e. an "immature metabolic pattern" (Berg et al. 1976; Kjessler & Berg 1976b).
With physiologically increasing amounts of circulating gonadotrophins the preferred metabolic pathway in vitro shifts in favour of 17α-OH-P, i. e. a "mature metabolic pattern". Such an alteration in the preferred in vitro metabolic pattern of [³H]progesterone has also been obtained by exogenous administration of gonadotrophins to a 47, XYY-male with an initially immature metabolic pattern (Berg & Kjessler 1976).
We have sequentially analysed the metabolism of [³H]progesterone in vitro in testicular incubates derived from a chromosomally normal male before and after 16 weeks of substitution therapy with gonadotrophic hormones.
The patient originally displayed an "immature" pattern of progesterone metabolites, i. e. the ratio 20α-DH-P/17é-OH-P was 3.04. After treatment with human menopausal gonadotrophins and hCG, the metabolic activity in total had increased, and the ratio 20é-DH-P/17é-OH-P had switched to 0.39.
These results confirm and extend the concept that gonadotrophic hormones may have a regulatory function on androgen biosynthesis by stimulating the oxidative metabolic pathway from progesterone to biologically active androgens via 17α-hydroxyprogesterone.