Intracrine androgen biosynthesis, metabolism and action revisited
File(s)
Published version
Author(s)
Schiffer, Lina
Arlt, Wiebke
Storbeck, Karl-Heinz
Type
Journal Article
Abstract
Androgens play an important role in metabolic homeostasis and reproductive health in both men and women. Androgen signalling is dependent on androgen receptor activation, mostly by testosterone and 5α-dihydrotestosterone. However, the intracellular or intracrine activation of C19 androgen precursors to active androgens in peripheral target tissues of androgen action is of equal importance. Intracrine androgen synthesis is often not reflected by circulating androgens but rather by androgen metabolites and conjugates. In this review we provide an overview of human C19 steroid biosynthesis including the production of 11-oxygenated androgens, their transport in circulation and uptake into peripheral tissues. We conceptualise the mechanisms of intracrinology and review the intracrine pathways of activation and inactivation in selected human tissues. The contribution of liver and kidney as organs driving androgen inactivation and renal excretion are also highlighted. Finally, the importance of quantifying androgen metabolites and conjugates to assess intracrine androgen production is discussed.
Date Issued
2018-04-15
Date Acceptance
2017-08-28
Citation
Molecular and Cellular Endocrinology, 2018, 465 (C), pp.4-26
ISSN
0303-7207
Publisher
Elsevier
Start Page
4
End Page
26
Journal / Book Title
Molecular and Cellular Endocrinology
Volume
465
Issue
C
Copyright Statement
© 2018 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/28865807
PII: S0303-7207(17)30452-5
Subjects
11-oxygenated androgens
5 17-BETA-HYDROXYSTEROID-DEHYDROGENASE AKR1C3
Androgens
Cell Biology
CONGENITAL ADRENAL-HYPERPLASIA
Endocrinology & Metabolism
FATTY-ACID ESTERS
HORMONE-BINDING GLOBULIN
Hormone-dependent cancer
HUMAN DELTA(4)-3-OXOSTEROID 5-BETA-REDUCTASE
Intracrinology
KETO REDUCTASE SUPERFAMILY
Life Sciences & Biomedicine
POLYCYSTIC-OVARY-SYNDROME
RESISTANT PROSTATE-CANCER
Science & Technology
Steroid biosynthesis
STEROID SULFATASE INHIBITORS
TANDEM-MASS-SPECTROMETRY
Testosterone
Publication Status
Published
Coverage Spatial
Ireland
Date Publish Online
2017-09-01