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Research Article Free access | 10.1172/JCI108796

Massive Extraglandular Aromatization of Plasma Androstenedione Resulting in Feminization of a Prepubertal Boy

David L. Hemsell, Clare D. Edman, James F. Marks, Pentti K. Siiteri, and Paul C. MacDonald

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics and Gynecology of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Pediatrics of the University of Texas Southwestern Medical School, Dallas, Texas 75235

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Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics and Gynecology of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Pediatrics of the University of Texas Southwestern Medical School, Dallas, Texas 75235

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Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics and Gynecology of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Pediatrics of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Find articles by Marks, J. in: JCI | PubMed | Google Scholar

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics and Gynecology of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Pediatrics of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Find articles by Siiteri, P. in: JCI | PubMed | Google Scholar

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics and Gynecology of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Pediatrics of the University of Texas Southwestern Medical School, Dallas, Texas 75235

Find articles by MacDonald, P. in: JCI | PubMed | Google Scholar

Published August 1, 1977 - More info

Published in Volume 60, Issue 2 on August 1, 1977
J Clin Invest. 1977;60(2):455–464. https://doi.org/10.1172/JCI108796.
© 1977 The American Society for Clinical Investigation
Published August 1, 1977 - Version history
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Abstract

This report describes the mechanism of origin and the quantity of estrogen produced in a prepubertal boy who developed severe feminization at 8 yr of age as the result of a heretofore undescribed metabolic abnormality. The clinical findings were gynecomastia and accelerated linear growth and bone maturation. At the time feminization developed, there were no signs of growth or development of the otherwise normal prepubertal male external genitalia or any increase of muscle mass that normally accompanies male puberty.

The hyperestrogenism was found to be the consequence of massive extraglandular conversion of plasma androstenedione to estrone. During a 6-mo period of study, the plasma production rate of androstenedione ranged from 1.2 to 1.6 mg/day. More than 55% of plasma androstenedione was metabolized by aromatization to estrone which, in turn, was extensively sulfurylated in the tissue sites of aromatization before its entry into the blood. Thus, estrone sulfate was the final product in the aromatizing sites, and the plasma production rate of estrone sulfate derived from plasma androstenedione was 782 μg/24 h.

The extent of extraglandular conversion of plasma androstenedione to estrone measured in this boy was 50 times that observed in two normal prepubertal boys. Moreover, 94% of the extraglandular aromatization occurred in extrahepatic sites. The metabolic clearance rate of plasma androstenedione, 2,380 liters/day per m2, was markedly increased in this boy. Approximately 1,500 liters of plasma androstenedione clearance was accounted for by extrahepatic, extraglandular aromatization. The fractional conversion of testosterone to estradiol, 0.16, was 50 times greater in this boy than that observed in normal young adult men. The total extent of aromatization of plasma prehormones was even greater in this boy inasmuch as evidence was obtained that aromatization of 16-hydroxysteroids, e.g. 16α-hydroxy androstenedione and 16α-hydroxy dehydroisoandrosterone (sulfate), resulted in estriol formation independent of estrone formation. Thus, extensive extrahepatic, extraglandular aromatization resulted in advanced feminization in this prepubertal boy by a previously undescribed metabolic abnormality.

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