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Cited by 90Hormonal and reproductive studiesAdrenal Hormones and DisordersSteroid Chemistry and Biochemistry

No evidence for hepatic conversion of dehydroepiandrosterone (DHEA) sulfate to DHEA: in vivo and in vitro studies

Hammer, Fabian, Subtil, Sandra, Lux, Philipp, Maser-Gluth, Christiane, Stewart, Paul M., Allolio, Bruno, Arlt, Wiebke·2005·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2004-2386
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Abstract

Dehydroepiandrosterone (DHEA) sulfate (DHEAS) is the most abundant steroid in the human circulation and is thought to be the circulating hydrophilic storage form of DHEA. It is generally accepted that DHEA and DHEAS inter-convert freely and continuously via hydroxysteroid sulfotransferases and steroid sulfatase and that only desulfated DHEA can be converted downstream to sex steroids. Here we analyzed DHEA/DHEAS interconversion in vivo and in vitro. We administered oral DHEA (100 mg) and iv DHEAS (25 mg) to eight healthy young men, resulting in similar increases in serum DHEAS compared with baseline. However, although DHEA administration significantly increased serum DHEA (P < 0.05), no such increase was observed after DHEAS. Similarly, DHEA but not DHEAS was converted downstream to androstenedione, estrone, and androstanediol glucuronide. The striking absence of conversion of DHEAS to DHEA was mirrored by our in vitro findings in HepG2 cells, revealing dose-dependent conversion of DHEA (0.1-2 mum) to DHEAS but no conversion of DHEAS (0.1-2 mum). These results clearly illustrate a lack of hepatic conversion of DHEAS to DHEA, challenging the concept of free interconversion of DHEA and DHEAS. DHEAS does not seem to represent a circulating storage pool for DHEA regeneration, and therefore serum DHEAS is unlikely to reflect bioavailable DHEA.

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Crossref · 10.1210/jc.2004-2386

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  • DHEAS is primarily thought to serve as an inactive waste product of adrenal steroidogenesis, produced to prevent an excessive androgen load.

    “However, it is primarily thought to serve as an inactive waste product of adrenal steroidogenesis, produced to prevent an excessive androgen load [39,40,279].”

    From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [279]

  • Administration of DHEA yields significant increases in both DHEAS and active androgens, while administration of DHEAS does not result in any increase of DHEA and downstream androgens in healthy adults.

    “However, while administration of DHEA yields significant increases in both DHEAS and active androgens (Arlt et al., 1998, Arlt et al., 1999b), the administration of DHEAS does not result in any increase of DHEA and downstream androgens in healthy adults (Hammer et al., 2005).”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Hammer et al., 2005

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Authors
Hammer, F., Subtil, S., Lux, P., Maser-Gluth, C., Stewart, P. M., Allolio, B., & Arlt, W.
Affiliations
  • University of Würzburg (DE)
  • Department of Pharmacology (C.M.-G.), University of Heidelberg, 69120 Heidelberg, Germany;
  • University of Birmingham (GB)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2005-06-01
Volume
90
Issue
6
Pages
3600-3605
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2004-2386
OpenAlex
W2104662014
Cited by
90
References
25
Citations by year
2026: 1 · 2025: 4 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 4
FWCI
3.52
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Keywords
dehydroepiandrosterone sulfate, dehydroepiandrosterone, hepatic steroid metabolism, hydroxysteroid sulfotransferase, steroid sulfatase, androstenedione, estrone, androstanediol glucuronide, HepG2 cells
MeSH terms
Adolescent, Adult, Biotransformation, Dehydroepiandrosterone, Humans, Liver, Male, Sulfotransferases, Body Mass Index, Polymerase Chain Reaction, Dehydroepiandrosterone Sulfate

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