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Dehydroepiandrosterone metabolism

C Longcope1

  • 1Department of Obstetrics/Gynecology, University of Massachuselts Medical School, Worcester 01655-0321, USA.

The Journal of Endocrinology
|September 1, 1996
PubMed
Summary
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Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are steroid hormones with differing blood clearance rates. These hormones interconvert and can be converted to androgens and estrogens in tissues, with DHEAS being a key source of ovarian testosterone.

Area of Science:

  • Endocrinology
  • Steroid Biochemistry

Background:

  • Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are key circulating steroid hormones.
  • Most DHEA and DHEAS in blood are protein-bound, with a small free fraction.
  • DHEA and DHEAS exhibit distinct metabolic clearance rates (MCRs), with DHEA being cleared much faster than DHEAS.

Purpose of the Study:

  • To elucidate the pharmacokinetic differences between DHEA and DHEAS.
  • To describe the interconversion and metabolic pathways of DHEA and DHEAS.
  • To highlight the role of DHEAS in ovarian steroidogenesis.

Main Methods:

  • Pharmacokinetic analysis of DHEA and DHEAS.
  • Metabolic clearance rate (MCR) determination.
  • Investigation of steroid hormone interconversion and peripheral tissue metabolism.

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Main Results:

  • DHEA has a high MCR (~2000 L/day), while DHEAS has a significantly lower MCR (~13 L/day).
  • DHEA and DHEAS readily interconvert, with DHEA converting to DHEAS (6%) and DHEAS converting to DHEA (60-70%).
  • Both hormones are precursors to androgens (androstenedione, testosterone, dihydrotestosterone) and estrogens via aromatization in peripheral tissues.

Conclusions:

  • DHEAS serves as a significant reservoir for DHEA due to its slower clearance and substantial interconversion.
  • DHEA and DHEAS are versatile precursors for various active steroid hormones.
  • DHEAS plays a crucial role within the ovarian follicle as a source of testosterone, impacting reproductive function.