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. 1970 Jan;49(1):31–40. doi: 10.1172/JCI106219

Studies on testosterone metabolism in subjects with testicular feminization syndrome

P Mauvais-Jarvis 1, J P Bercovici 1, O Crepy 1, F Gauthier 1
PMCID: PMC322441  PMID: 5409806

Abstract

The metabolism of radioactive testosterone simultaneously administered intravenously and either orally or percutaneously has been studied in seven patients with the syndrome of testicular feminization and compared with that of normal males and females. This investigation was carried out in order to determine the relative contribution to urinary 17-oxo and 17β-hydroxy androstane steroids of labeled testosterone, according to its mode of administration. In normal males the yields of urinary 5α-androstane-3α,17β-diol (androstanediol) originating from either an intravenous or a percutaneous dose of testosterone were respectively 3 and 6 times higher than those arising from an oral dose which perfuses the liver directly. These data indicate that in normal males, testosterone might be 5α-hydrogenated outside the liver. By contrast in patient with feminizing testes, because the contribution to androstanediol of radioactive testosterone is identical whatever its mode of administration, the extrahepatic 5α-reduction of this substrate seems very unlikely.

The metabolic abnormalities observed in patients with testicular feminization syndrome may be reproduced in normal males by estrogen treatment. Nevertheless, the sensitivity of the patients to estrogen seems to be 10 times greater than that of normal males. This sensitivity was appreciated from the reduction of radioactive testosterone intravenously injected to urinary 17β-hydroxy-5α-androstan-3-one and androstanediol and also from the level of plasma binding for testosterone. This level was significantly higher (P < 0.05) in patients with feminizing testes than in normal males. The level increased dramatically after administration of a low dose of estrogen whereas this effect was not observed in normal males under the same experimental conditions.

In light of these results the defect of extrahepatic 5α-reduction of testosterone observed in patients with feminizing testes does not necessarily reflect an enzymatic impairment but might be related to an abnormal synthesis of plasma binding protein(s) under the effect of circulating estrogens so that an abnormally small amount of unbound testosterone may be available in target cells for 5α-reduction.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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