title: Defects in steroidogenic enzymes. Discrepancies between clinical steroid research and molecular biology results.
abstract: Molecular biology has clarified the understanding of steroidogenic enzyme genetics. Nevertheless, there are discrepancies between fundamental and clinical experience. (1) Why do patients with "pure" 17 alpha-hydroxylase or 17,20-desmolase deficiency exist, when one cytochrome regulates both steps? A case of interest is discussed, who had "pure" 17,20-desmolase deficiency until adolescence, but additional 17 alpha-hydroxylase deficiency thereafter. (2) In 11 beta-hydroxylase deficiency, it was puzzling to find 18-hydroxylated compounds, and, in isolated hypoaldosteronism, normal cortisol, since 11 beta- and 18-hydroxylation were thought to be regulated together. This has now been explained by differences in the fasciculata and glomerulosa. The occurrence of 11 beta-hydroxylase deficiency of 17-hydroxylated steroids only, however, remains enigmatic. (3) 3 beta-Hydroxysteroid dehydrogenase deficiency does not only seem to exist in classic (mutations of type II gene), but also in late-onset cases. In them, no molecular basis could be found. (4) Also, in cholesterol side-chain cleavage, there is an inequity: while evidently one cytochrome regulates 20- and 22-hydroxylation, pregnenolone is formed when 20 alpha OH-cholesterol, but not when cholesterol, is added to adrenal tissue of deficient patients. Other factors (promoters, fusion proteins, adrenodoxin, cAMP-dependent expression of genes, and/or proteases), or hormonal replacement in patients may be responsible for these discrepancies.
authors.affiliation: Department of Pediatrics, University of Zurich, Kinderspital, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Zachmann
mesh_terms: D000312:Adrenal Hyperplasia, Congenital; D000446:Aldehyde-Lyases / Q000172:deficiency / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000172:deficiency / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency / Q000235:genetics; D006801:Humans; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000172:deficiency* / Q000235:genetics*; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D000446:Aldehyde-Lyases