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Document 7 <strong>Structure</strong>—Function Relationships in Hydroxysteroid Dehydrogenases Igor Tsigelny and Michael E. Baker University of California, San Diego, La Jolla, California I. Introduction Page 191 Steroid hormones regulate a multitude of physiological processes in humans. Androgens and estrogens regulate sexual development and reproduction; glucocorticoids are important in the response to stress; vitamin D is important in bone growth; progestins are important for a viable fetus during pregnancy; mineralocorticoids regulate sodium and potassium balance to maintain normal blood pressure. Moreover, the growth of some breast and prostate tumors depends on steroids. With this multitude of medically important steroid-dependent actions, much research has gone into understanding their mode of action, with most of the effort concerned with the receptors that mediate the actions of steriods. A. High Blood Pressure and 11β-Hydroxysteroid Dehydrogenase It is only in the last decade that the role of hydroxysteroid dehydrogenases (Figure 1) in regulating the actions of steroids has been appreciated [1–6]. This mechanism for regulating steroid hormone action was uncovered in several laboratories studying various aspects of high blood pressure. One source was the study in the 1970s that identified the syndrome, Apparent Mineralocorticoid Excess (AME), a genetic disease that results in high blood pressure in children [7–10]. Also important is the work from laboratories investigating paradoxes in the mechanism of action of aldosterone in the kidney [1–4,9,10]. These studies identified 11β-hydroxysteroid dehydrogenase (11β-HSD) as a key enzyme. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_191.html [4/5/2004 5:04:54 PM]
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