Semin Reprod Med 2004; 22(4): 281-288
DOI: 10.1055/s-2004-861545
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Overview of Dehydroepiandrosterone Biosynthesis

Richard J. Auchus1
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
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Publication History

Publication Date:
05 January 2005 (online)

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ABSTRACT

The biosynthesis of dehydroepiandrosterone (DHEA) from cholesterol involves only two enzymes, both cytochrome P450s. The conversion of cholesterol to pregnenolone is mediated by cholesterol side-chain cleavage enzyme (CYP11A1), which is found in the mitochondria. The cleavage of pregnenolone to DHEA requires both the 17α-hydroxylase and 17,20-lyase activities of CYP17, which is found in the endoplasmic reticulum. These conversions require pairs of electron transfer proteins or redox partners, which are adrenodoxin and adrenodoxin reductase for CYP11A1 and cytochrome P450-oxidoreductase and cytochrome b5 for CYP17. In addition, the steroidogenic acute regulatory (StAR) protein regulates the flux of cholesterol into the biosynthetic pathway and represents the mechanism of acute regulation. Finally, in addition to possessing CYP11A1 and CYP17, it is equally important that a steroidogenic cell not contain other enzymes that drain the flux of pregnenolone to DHEA. These characteristics are illustrated by the fetal adrenal cortex and the zona reticularis, which are dedicated to the synthesis of DHEA and DHEA-sulfate.

REFERENCES

Richard J AuchusM.D. Ph.D. 

5323 Harry Hines Blvd., Dallas

TX 75390-8857

Email: richard.auchus@UTSouthwestern.edu