Document Detail

Age-specific changes in sex steroid biosynthesis and sex development.
MedLine Citation:
PMID:  17875487     Owner:  NLM     Status:  MEDLINE    
Normal male sex development requires the SRY gene on the Y chromosome, the regression of Müllerian structures via anti-Müllerian hormone (AMH) signalling, the development of the Wolffian duct system into normal male internal genital structures consequent to testosterone secretion by the testicular Leydig cells, and finally, sufficient activation of testosterone to dihydrotestosterone by 5alpha-reductase. All these events take place during weeks 8-12 of gestation, a narrow window of sexual differentiation. Recent studies in human fetal development have demonstrated the early fetal expression of the adrenocorticotrophic hormone (ACTH) receptor and all steroidogenic components necessary for the biosynthesis of cortisol. These findings provide compelling evidence for the assumed pathogenesis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, diminished feedback to the pituitary due to glucocorticoid deficiency, subsequent ACTH excess, and up-regulation of adrenal androgen production with subsequent virilization. Another CAH variant, P450 oxidoreductase deficiency, manifests with 46,XX disorder of sex development (DSD), i.e., virilized female genitalia, despite concurrently low circulating androgens. This CAH variant illustrates the existence of an alternative pathway toward the biosynthesis of active androgens in humans which is active in human fetal life only. Thus CAH teaches important lessons from nature, providing privileged insights into the window of human sexual differentiation, and particularly highlighting the importance of steroidogenesis in the process of human sexual differentiation.
Nils Krone; Neil A Hanley; Wiebke Arlt
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Best practice & research. Clinical endocrinology & metabolism     Volume:  21     ISSN:  1521-690X     ISO Abbreviation:  Best Pract. Res. Clin. Endocrinol. Metab.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-18     Completed Date:  2007-11-30     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101120682     Medline TA:  Best Pract Res Clin Endocrinol Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  393-401     Citation Subset:  IM    
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MeSH Terms
Adrenal Hyperplasia, Congenital / classification,  embryology,  metabolism
Aging / metabolism
Feedback, Physiological
Gonadal Dysgenesis, 46,XX / classification,  embryology*,  metabolism
Gonadal Steroid Hormones / biosynthesis*,  physiology*
Hypothalamo-Hypophyseal System / embryology,  physiology
NADPH-Ferrihemoprotein Reductase / deficiency
Pituitary-Adrenal System / embryology,  physiology
Sexual Development* / genetics,  physiology
Steroid 21-Hydroxylase / biosynthesis
Grant Support
G116/172//Medical Research Council
Reg. No./Substance:
0/Gonadal Steroid Hormones; EC 21-Hydroxylase; EC Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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