Incomplete masculinization due to a deficiency of 17 beta-hydroxysteroid dehydrogenase: comparison of prepubertal and peripubertal siblings.
Incomplete masculinization due to a deficiency of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was investigated in siblings aged 4 years (Case 1) and 12 years (Case 2). Diagnosis was based on increased ratios of androstenedione (A) to testosterone (T) in blood, and impaired reduction of A to T by 17 beta-HSD in vitro in the testes. Impairment was total in Case 2 but partial in Case 1. Case 2 also showed deficient conversion of dehydroepiandrosterone (DHA) to androstenediol and of oestrone to oestradiol by 17 beta-HSD which were normal in Case 1. Oxidation of T to A by 17 beta-HSD and conversion of 17 alpha-hydroxyprogesterone to A by 17,20 desmolase were normal in the testes of both siblings. 3 beta-HSD conversion of DHA to A was normal in Case 1, but markedly increased in Case 2. In contrast to testicular findings, 17 beta-HSD reduction of A to T in genital skin fibroblasts from Case 2 was normal and diagnosis would not have been possible from studies of measurements of this enzyme in skin. The severity of the testicular 17 beta-HSD deficiency in the peripubertal compared with the prepubertal sibling suggests either considerable intra-familial variation in the extent of the enzyme defect or that puberty may aggravate this disorder. The normal reductive action of 17 beta-HSD in skin, despite impaired action in testes, suggests involvement of more than one iso-enzyme.
Wilson
S C
SC
Division of Steroid Endocrinology, University of Leeds.
Hodgins
M B
MB
Scott
J S
JS
D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000446:Aldehyde-Lyases / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D012734:Disorders of Sex Development / Q000201:enzymology*; D005837:Genitalia, Male / Q000201:enzymology; D006801:Humans; D008297:Male; D011627:Puberty; D012867:Skin / Q000201:enzymology; D013254:Steroid 17-alpha-Hydroxylase; D013737:Testis / Q000201:enzymology
D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)); D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases