| Age-specific changes in sex steroid biosynthesis and sex development. | |
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MedLine Citation:
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PMID: 17875487 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Nils Krone; Neil A Hanley; Wiebke Arlt |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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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:
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Created Date: 2007-09-18 Completed Date: 2007-11-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101120682 Medline TA: Best Pract Res Clin Endocrinol Metab Country: England |
Other Details:
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Languages: eng Pagination: 393-401 Citation Subset: IM |
Affiliation:
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Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Hyperplasia, Congenital
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classification,
embryology,
metabolism Aging / metabolism Animals Feedback, Physiological Female Gonadal Dysgenesis, 46,XX / classification, embryology*, metabolism Gonadal Steroid Hormones / biosynthesis*, physiology* Humans Hypothalamo-Hypophyseal System / embryology, physiology Male NADPH-Ferrihemoprotein Reductase / deficiency Pituitary-Adrenal System / embryology, physiology Sexual Development* / genetics, physiology Steroid 21-Hydroxylase / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Gonadal Steroid Hormones; EC 1.14.99.10/Steroid 21-Hydroxylase; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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