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5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis

  • Abdulmaged M. Traish EMAIL logo , Andre T. Guay and Michael Zitzmann
Published/Copyright: October 14, 2014
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 20 Issue 3

Abstract

5α-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 5α-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 5α-reductase activities and reduce the clearance of glucocorticoids and mineralocorticoids, potentiating insulin resistance, diabetes and vascular disease.

Keywords: 5α-reductases; cardiovascular disease; diabetes; glucocorticoids; insulin resistance
Corresponding author: Abdulmaged M. Traish, Departments of Biochemistry and Urology, Boston University School of Medicine, 715 Albany Street, A502, Boston, MA 02118, USA, Phone: +617 638 4578, Fax: +617 638 5412, E-mail:

Acknowledgments

This work was solely supported by the Department of Urology, Boston University School of Medicine.

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Received: 2014-8-27
Accepted: 2014-9-9
Published Online: 2014-10-14
Published in Print: 2014-12-1

©2014 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Letter to the Editor
  3. Acute mental feelings and professional stress are controlling health. Mechanism and role of hormones and “solvated electrons” (eaq–)
  4. Review Article
  5. 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis
  6. Original Articles
  7. The potent inhibition of human cytosolic sulfotransferase 1A1 by 17α-ethinylestradiol is due to interactions with isoleucine 89 on loop 1
  8. In women, no significant variances of calculated free testosterone (cFT) are observed when a fixed value of albumin (Alb: 4.3 g/dL) is used instead of measured albumin values
  9. Regulation of flavin-containing mono-oxygenase (Fmo3) gene expression by steroids in mice and humans
https://doi.org/10.1515/hmbci-2014-0025
Keywords for this article
5α-reductases; cardiovascular disease; diabetes; glucocorticoids; insulin resistance

Articles in the same Issue

  1. Frontmatter
  2. Letter to the Editor
  3. Acute mental feelings and professional stress are controlling health. Mechanism and role of hormones and “solvated electrons” (eaq–)
  4. Review Article
  5. 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis
  6. Original Articles
  7. The potent inhibition of human cytosolic sulfotransferase 1A1 by 17α-ethinylestradiol is due to interactions with isoleucine 89 on loop 1
  8. In women, no significant variances of calculated free testosterone (cFT) are observed when a fixed value of albumin (Alb: 4.3 g/dL) is used instead of measured albumin values
  9. Regulation of flavin-containing mono-oxygenase (Fmo3) gene expression by steroids in mice and humans
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