Journal
HORMONE MOLECULAR BIOLOGY AND CLINICAL INVESTIGATION
Volume 20, Issue 3, Pages 73-80Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/hmbci-2014-0025
Keywords
5 alpha-reductases; cardiovascular disease; diabetes; glucocorticoids; insulin resistance
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Funding
- Department of Urology, Boston University School of Medicine
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5 alpha-reductases, a unique family of enzymes with a wide host of substrates and tissue distributions, play a key role in the metabolism of androgens, progestins, mineralocorticoids and glucocorticoids. These enzymes are the rate-limiting step in the synthesis of a host of neurosteroids, which are critical for central nervous system function. Androgens and glucocorticoids modulate mitochondrial function, carbohydrate, protein and lipid metabolism and energy balance. Thus, the inhibition of these regulatory enzymes results in an imbalance in steroid metabolism and clearance rates, which leads to altered physiological processes. In this report, we advance the hypothesis that inhibition of 5 alpha-reductases by finasteride and dutasteride alters not only steroid metabolism but also interferes with the downstream actions and signaling of these hormones. We suggest that finasteride and dutasteride inhibit 5 alpha-reductase activities and reduce the clearance of glucocorticoids and mineralocorticoids, potentiating insulin resistance, diabetes and vascular disease.
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