Recent aspects of steroid biosynthesis in male sex differentiation. Clinical studies.
Recent discoveries in molecular biology have much clarified the regulation and function of steroid-converting enzymes. Most progress has been made in the area of cytochromes, which regulate the side chain cleavage of cholesterol (P-450 SCC) and the 17 alpha-hydroxylase and 17,20-desmolase (or 17,20-lyase) activities (P-450 17 alpha), as well as in 3 beta-hydroxysteroid dehydrogenase. Nevertheless, there are some discrepancies between fundamental knowledge and clinical experience, which are difficult to understand: why is it for example possible that cases with 'pure' 17 alpha-hydroxylase or 17,20-desmolase deficiency exist, when there is only one cytochrome regulating both steps? After a brief review of clinical and biochemical findings in the various defects of testosterone biosynthesis, a case is discussed, which is of interest in this respect. This XY patient with female external genitalia, who has been shown to have compound heterozygous mutations, had 'pure' 17,20-desmolase deficiency up to adolescence, but additional 17 alpha-hydroxylase deficiency with hypertension developed thereafter. From this observation, it has to be concluded that as yet unknown, possibly age-dependent modulating factors exist, which influence the activity of the cytochrome. Also the estrogen replacement given to the patient might have played a role in this change.
Zachmann
M
M
Department of Pediatrics, University of Zurich, Switzerland.
D000312:Adrenal Hyperplasia, Congenital; D000328:Adult; D000446:Aldehyde-Lyases / Q000172:deficiency; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency; D012734:Disorders of Sex Development / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D012733:Sex Differentiation / Q000235:genetics / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis*
D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D000446:Aldehyde-Lyases