Intracrine androgen biosynthesis, metabolism and action revisited

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...

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Bibliographic Details
Published inMolecular and cellular endocrinology Vol. 465; pp. 4 - 26
Main Authors Schiffer, Lina, Arlt, Wiebke, Storbeck, Karl-Heinz
Format Journal Article
LanguageEnglish
Published Ireland Elsevier B.V 15.04.2018
North Holland Publishing
Subjects
11-oxygenated androgens
androgen receptors
Androgens
Androgens - biosynthesis
Androgens - metabolism
Animals
biosynthesis
Biosynthetic Pathways
excretion
homeostasis
Hormone-dependent cancer
Humans
Intracrinology
kidneys
liver
men
metabolites
Organ Specificity
Reproduction
Steroid biosynthesis
Steroids - biosynthesis
Testosterone
women
DHEA
PREG
UGT
E1S
17αHP
11-oxygenated androgens
E1
E2
SULT
DHT
PAPS
A4
DHEAS
STS
PORD
T
StAR
3α-adiol
HSD
CYP
CHOL
11KT
11OHDHT
5-diol
17OHPROG
AST
Pdiol
AKR
OATP
5α-dione
Steroid biosynthesis
Hormone-dependent cancer
Testosterone
AR
Androgens
11OHT
PCOS
ETIO
Intracrinology
11KDHT
11KA4
EpiT
11OHA4
SHBG
CRPC
EpiAST
PROG
Online AccessGet full text

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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. •Serum concentrations of active androgens do not account for all androgen activity.•Dysregulation of intracrine androgen pathways is relevant to numerous disease states.•Androgen metabolites and conjugates can be of diagnostic value.•11-oxygenated C19 steroids contribute to the androgen pool.•11βHSD enzymes are important modulators of both glucocorticoid and androgen activity.
AbstractList 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.
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 C 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 C 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.
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 C 19 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 C 19 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. • Serum concentrations of active androgens do not account for all androgen activity. • Dysregulation of intracrine androgen pathways is relevant to numerous disease states. • Androgen metabolites and conjugates can be of diagnostic value. • 11-oxygenated C 19 steroids contribute to the androgen pool. • 11βHSD enzymes are important modulators of both glucocorticoid and androgen activity.
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. •Serum concentrations of active androgens do not account for all androgen activity.•Dysregulation of intracrine androgen pathways is relevant to numerous disease states.•Androgen metabolites and conjugates can be of diagnostic value.•11-oxygenated C19 steroids contribute to the androgen pool.•11βHSD enzymes are important modulators of both glucocorticoid and androgen activity.
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.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.
Author Storbeck, Karl-Heinz
Arlt, Wiebke
Schiffer, Lina
AuthorAffiliation b Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa
a Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
AuthorAffiliation_xml – name: b Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa
– name: a Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Author_xml – sequence: 1
  givenname: Lina
  surname: Schiffer
  fullname: Schiffer, Lina
  organization: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
– sequence: 2
  givenname: Wiebke
  orcidid: 0000-0001-5106-9719
  surname: Arlt
  fullname: Arlt, Wiebke
  email: w.arlt@bham.ac.uk
  organization: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
– sequence: 3
  givenname: Karl-Heinz
  orcidid: 0000-0003-1669-6383
  surname: Storbeck
  fullname: Storbeck, Karl-Heinz
  organization: Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28865807$$D View this record in MEDLINE/PubMed
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Thu Apr 24 23:00:35 EDT 2025
Fri Feb 23 02:20:49 EST 2024
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Keywords DHEA
PREG
UGT
E1S
17αHP
11-oxygenated androgens
E1
E2
SULT
DHT
PAPS
A4
DHEAS
STS
PORD
T
StAR
3α-adiol
HSD
CYP
CHOL
11KT
11OHDHT
5-diol
17OHPROG
AST
Pdiol
AKR
OATP
5α-dione
Steroid biosynthesis
Hormone-dependent cancer
Testosterone
AR
Androgens
11OHT
PCOS
ETIO
Intracrinology
11KDHT
11KA4
EpiT
11OHA4
SHBG
CRPC
EpiAST
PROG
Language English
License This is an open access article under the CC BY license.
Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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PublicationTitle Molecular and cellular endocrinology
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Snippet Androgens play an important role in metabolic homeostasis and reproductive health in both men and women. Androgen signalling is dependent on androgen receptor...
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SubjectTerms 11-oxygenated androgens
androgen receptors
Androgens
Androgens - biosynthesis
Androgens - metabolism
Animals
biosynthesis
Biosynthetic Pathways
excretion
homeostasis
Hormone-dependent cancer
Humans
Intracrinology
kidneys
liver
men
metabolites
Organ Specificity
Reproduction
Steroid biosynthesis
Steroids - biosynthesis
Testosterone
women
Title Intracrine androgen biosynthesis, metabolism and action revisited
URI https://dx.doi.org/10.1016/j.mce.2017.08.016
https://www.ncbi.nlm.nih.gov/pubmed/28865807
https://www.proquest.com/docview/1935389210
https://www.proquest.com/docview/2010217805
https://pubmed.ncbi.nlm.nih.gov/PMC6565845
Volume 465
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