Hemsell D L, Edman C D, Marks J F, Siiteri P K, MacDonald P C
J Clin Invest. 1977 Aug;60(2):455-64. doi: 10.1172/JCI108796.
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 mug/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 m(2), 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. 16alpha-hydroxy androstenedione and 16alpha-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.
本报告描述了一名青春期前男孩雌激素产生的机制及数量。该男孩因一种前所未有的代谢异常，在8岁时出现严重女性化。临床发现为乳腺增生、线性生长加速和骨骼成熟加快。女性化出现时，这个原本正常的青春期前男性外生殖器没有生长或发育的迹象，也没有伴随男性青春期通常出现的肌肉量增加。发现高雌激素血症是血浆雄烯二酮大量在腺体外转化为雌酮的结果。在为期6个月的研究期间，雄烯二酮的血浆生成率为1.2至1.6毫克/天。超过55%的血浆雄烯二酮通过芳香化作用代谢为雌酮，而雌酮在进入血液之前，在芳香化的组织部位被广泛硫酸化。因此，硫酸雌酮是芳香化部位的最终产物，由血浆雄烯二酮衍生的硫酸雌酮的血浆生成率为782微克/24小时。在这个男孩身上测得的血浆雄烯二酮向雌酮的腺体外转化程度是两个正常青春期前男孩的50倍。此外，94%的腺体外芳香化发生在肝外部位。这个男孩血浆雄烯二酮的代谢清除率为2380升/天·平方米，明显升高。约1500升血浆雄烯二酮清除是由肝外、腺体外芳香化作用所致。该男孩睾酮向雌二醇的转化率为0.16，是正常年轻成年男性的50倍。这个男孩血浆前体激素的总芳香化程度甚至更高，因为有证据表明16-羟基类固醇（如16α-羟基雄烯二酮和16α-羟基脱氢异雄酮（硫酸盐））的芳香化作用会导致雌三醇形成，且与雌酮形成无关。因此，广泛的肝外、腺体外芳香化作用通过一种前所未有的代谢异常，导致了这个青春期前男孩的早熟女性化。
