|
|
J Clin Invest. 1970 January; 49(1): 31–40. doi: 10.1172/JCI106219. | PMCID: PMC322441 |
Studies on testosterone metabolism in subjects with testicular feminization syndrome P. Mauvais-Jarvis, J. P. Bercovici, O. Crepy, and F. Gauthier 1Laboratoire de Chimie Biologique, C.H.U. La Pitié, Paris 13, France 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. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. These references are in PubMed. This may not be the complete list of references from this article. - French FS, Van Wyk JJ, Baggett B, Easterling WE, Talbert LM, Johnston FR, Forchielli E, Dey AC. Further evidence of a target organ defect in the syndrome of testicular feminization. J Clin Endocrinol Metab. 1966 May;26(5):493–503. [PubMed]
- Rivarola MA, Saez JM, Meyer WJ, Kenny FM, Migeon CJ. Studies of androgens in the syndrome of male pseudohermaphroditism with testicular feminization. J Clin Endocrinol Metab. 1967 Mar;27(3):371–378. [PubMed]
- Mauvais-Jarvis P. Etude du métabolisme 17-beta-hydroxylé de la testostérone en fonction de la différenciation sexuelle humaine. C R Acad Sci Hebd Seances Acad Sci D. 1966 Jun 27;262(26):2753–2756. [PubMed]
- Mauvais-Jarvis P, Floch HH, Bercovici JP. Studies on testosterone metabolism in human subjects with normal and pathological sexual differentiation. J Clin Endocrinol Metab. 1968 Apr;28(4):460–471. [PubMed]
- Mauvais-Jarvis P, Bercovici JP, Floch HH. Influence des hormones sexuelles sur le métabolisme des androgènes. Rev Fr Etud Clin Biol. 1969 Feb;14(2):159–168. [PubMed]
- FARNSWORTH WE, BROWN JR. TESTOSTERONE METABOLISM IN THE PROSTATE. Natl Cancer Inst Monogr. 1963 Oct;12:323–329. [PubMed]
- Chamberlain J, Jagarinec N, Ofner P. Catabolism of [4-14C]testosterone by subcellular fractions of human prostate. Biochem J. 1966 Jun;99(3):610–616. [PubMed]
- Bruchovsky N, Wilson JD. The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one by rat prostate in vivo and in vitro. J Biol Chem. 1968 Apr 25;243(8):2012–2021. [PubMed]
- Anderson KM, Liao S. Selective retention of dihydrotestosterone by prostatic nuclei. Nature. 1968 Jul 20;219(5151):277–279. [PubMed]
- Mauvais-Jarvis P, Bercovici JP, Gauthier F. In vivo studies on testosterone metabolism by skin of normal males and patients with the syndrome of testicular feminization. J Clin Endocrinol Metab. 1969 Mar;29(3):417–421. [PubMed]
- BAULIEU EE, MAUVAIS-JARVIS P. STUDIES ON TESTOSTERONE METABOLISM. I. CONVERSION OF TESTOSTERONE-17-ALPHA-3H TO 5-ALPHA- AND 5-BETA-ANDROSTANE-3-ALPHA, 17-BETA-DEOL-17-ALPHA-3H: A NEW "17-BETA-HYDROXYL PATHWAY". J Biol Chem. 1964 May;239:1569–1577. [PubMed]
- Mauvais-Jarvis P, Floch H, Jung I, Robel P, Baulieu EE. Studies on testosterone metabolism. VI. Precursors of urinary androstanediols. Steroids. 1968 Feb;11(2):207–224. [PubMed]
- Pearlman WH, Crépy O. Steroid-protein interaction with particular reference to testosterone binding by human serum. J Biol Chem. 1967 Jan 25;242(2):182–189. [PubMed]
- Rongone EL. Testosterone metabolism by human male mammary skin. I. Steroids. 1966 Jun;7(6):489–504. [PubMed]
- Gomez EC, Hsia SL. In vitro metabolism of testosterone-4-14C and delta-4-androstene-3,17-dione-4-14C in human skin. Biochemistry. 1968 Jan;7(1):24–32. [PubMed]
- Wilson JD, Walker JD. The conversion of testosterone to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone) by skin slices of man. J Clin Invest. 1969 Feb;48(2):371–379. [PubMed]
- Northcutt RC, Island DP, Liddle GW. An explanation for the target organ unresponsiveness to testosterone in the testicular feminization syndrome. J Clin Endocrinol Metab. 1969 Mar;29(3):422–425. [PubMed]
- Longcope Christopher, Layne Donald S, Tait James F. Metabolic clearance rates and interconversions of estrone and 17beta-estradiol in normal males and females. J Clin Invest. 1968 Jan;47(1):93–106. [PubMed]
- MacDonald PC, Rombaut RP, Siiteri PK. Plasma precursors of estrogen. I. Extent of conversion of plasma delta-4-androstenedione to estrone in normal males and nonpregnant normal, castrate and adrenalectomized females. J Clin Endocrinol Metab. 1967 Aug;27(8):1103–1111. [PubMed]
- Pearlman WH, Crépy O, Murphy M. Testosterone-binding levels in the serum of women during the normal menstrual cycle, pregnancy, and the post-partum period. J Clin Endocrinol Metab. 1967 Jul;27(7):1012–1018. [PubMed]
- Rosner W, Deakins SM. Testosterone-binding globulins in human plasma: studies on sex distribution and specificity. J Clin Invest. 1968 Sep;47(9):2109–2116. [PubMed]
- Southren AL, Tochimoto S, Carmody NC, Isurugi K. Plasma production rates of testosterone in normal adult men and women and in patients with the syndrome of feminizing testes. J Clin Endocrinol Metab. 1965 Nov;25(11):1441–1450. [PubMed]
|
This article has been