Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells: role of AMPK and MAPK kinase pathways

Manjunath Ramanjaneya, Alex C. Conner, James Brown, Jing Chen, Janet E. Digby, Thomas M. Barber, Hendrik Lehnert, Harpal S. Randeva

Research output: Contribution to journalArticle

Abstract

Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production. A key rate-limiting step in steroidogenesis is cholesterol transportation across the mitochondrial membrane by steroidogenic acute regulatory protein (StAR). Several signalling pathways regulate StAR expression. The actions of adiponectin and its role in human adrenocortical steroid biosynthesis are not fully understood. The aim of this study was to investigate the effects of adiponectin on StAR protein expression, steroidogenic genes, and cortisol production and to dissect the signalling cascades involved in the activation of StAR expression. Using qRT-PCR, Western blot analysis and ELISA, we have demonstrated that stimulation of human adrenocortical H295R cells with adiponectin results in increased cortisol secretion. This effect is accompanied by increased expression of key steroidogenic pathway genes including StAR protein expression via ERK1/2 and AMPK-dependent pathways. This has implications for our understanding of adiponectin receptor activation and peripheral steroidogenesis. Finally, our study aims to emphasise the key role of adipokines in the integration of metabolic activity and energy balance partly via the regulation of adrenal steroid production.
LanguageEnglish
Pages802-809
Number of pages9
JournalBBA - Molecular Cell Research
Volume1813
Issue number5
Early online date18 Feb 2011
DOIs
Publication statusPublished - May 2011

Fingerprint

Adipokines
Adiponectin
Mitogen-Activated Protein Kinase Kinases
Hydrocortisone
Steroids
Adiponectin Receptors
AMP-Activated Protein Kinases
Mitochondrial Membranes
Neuropeptides
Western Blotting
Enzyme-Linked Immunosorbent Assay
Cholesterol
Gene Expression
Polymerase Chain Reaction
steroidogenic acute regulatory protein
AMP-activated protein kinase kinase
Genes

Keywords

  • steroidogenesis
  • MAPK
  • AMPK
  • adiponectin
  • cortisol
  • StAR

Cite this

Ramanjaneya, Manjunath ; Conner, Alex C. ; Brown, James ; Chen, Jing ; Digby, Janet E. ; Barber, Thomas M. ; Lehnert, Hendrik ; Randeva, Harpal S. / Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells : role of AMPK and MAPK kinase pathways. In: BBA - Molecular Cell Research. 2011 ; Vol. 1813, No. 5. pp. 802-809.
@article{1eba173d34004d378b5efe4f71e59e75,
title = "Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells: role of AMPK and MAPK kinase pathways",
abstract = "Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production. A key rate-limiting step in steroidogenesis is cholesterol transportation across the mitochondrial membrane by steroidogenic acute regulatory protein (StAR). Several signalling pathways regulate StAR expression. The actions of adiponectin and its role in human adrenocortical steroid biosynthesis are not fully understood. The aim of this study was to investigate the effects of adiponectin on StAR protein expression, steroidogenic genes, and cortisol production and to dissect the signalling cascades involved in the activation of StAR expression. Using qRT-PCR, Western blot analysis and ELISA, we have demonstrated that stimulation of human adrenocortical H295R cells with adiponectin results in increased cortisol secretion. This effect is accompanied by increased expression of key steroidogenic pathway genes including StAR protein expression via ERK1/2 and AMPK-dependent pathways. This has implications for our understanding of adiponectin receptor activation and peripheral steroidogenesis. Finally, our study aims to emphasise the key role of adipokines in the integration of metabolic activity and energy balance partly via the regulation of adrenal steroid production.",
keywords = "steroidogenesis, MAPK, AMPK, adiponectin, cortisol, StAR",
author = "Manjunath Ramanjaneya and Conner, {Alex C.} and James Brown and Jing Chen and Digby, {Janet E.} and Barber, {Thomas M.} and Hendrik Lehnert and Randeva, {Harpal S.}",
year = "2011",
month = "5",
doi = "10.1016/j.bbamcr.2011.02.010",
language = "English",
volume = "1813",
pages = "802--809",
journal = "BBA - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "5",

}

Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells : role of AMPK and MAPK kinase pathways. / Ramanjaneya, Manjunath; Conner, Alex C.; Brown, James; Chen, Jing; Digby, Janet E.; Barber, Thomas M.; Lehnert, Hendrik; Randeva, Harpal S.

In: BBA - Molecular Cell Research, Vol. 1813, No. 5, 05.2011, p. 802-809.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells

T2 - BBA - Molecular Cell Research

AU - Ramanjaneya, Manjunath

AU - Conner, Alex C.

AU - Brown, James

AU - Chen, Jing

AU - Digby, Janet E.

AU - Barber, Thomas M.

AU - Lehnert, Hendrik

AU - Randeva, Harpal S.

PY - 2011/5

Y1 - 2011/5

N2 - Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production. A key rate-limiting step in steroidogenesis is cholesterol transportation across the mitochondrial membrane by steroidogenic acute regulatory protein (StAR). Several signalling pathways regulate StAR expression. The actions of adiponectin and its role in human adrenocortical steroid biosynthesis are not fully understood. The aim of this study was to investigate the effects of adiponectin on StAR protein expression, steroidogenic genes, and cortisol production and to dissect the signalling cascades involved in the activation of StAR expression. Using qRT-PCR, Western blot analysis and ELISA, we have demonstrated that stimulation of human adrenocortical H295R cells with adiponectin results in increased cortisol secretion. This effect is accompanied by increased expression of key steroidogenic pathway genes including StAR protein expression via ERK1/2 and AMPK-dependent pathways. This has implications for our understanding of adiponectin receptor activation and peripheral steroidogenesis. Finally, our study aims to emphasise the key role of adipokines in the integration of metabolic activity and energy balance partly via the regulation of adrenal steroid production.

AB - Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production. A key rate-limiting step in steroidogenesis is cholesterol transportation across the mitochondrial membrane by steroidogenic acute regulatory protein (StAR). Several signalling pathways regulate StAR expression. The actions of adiponectin and its role in human adrenocortical steroid biosynthesis are not fully understood. The aim of this study was to investigate the effects of adiponectin on StAR protein expression, steroidogenic genes, and cortisol production and to dissect the signalling cascades involved in the activation of StAR expression. Using qRT-PCR, Western blot analysis and ELISA, we have demonstrated that stimulation of human adrenocortical H295R cells with adiponectin results in increased cortisol secretion. This effect is accompanied by increased expression of key steroidogenic pathway genes including StAR protein expression via ERK1/2 and AMPK-dependent pathways. This has implications for our understanding of adiponectin receptor activation and peripheral steroidogenesis. Finally, our study aims to emphasise the key role of adipokines in the integration of metabolic activity and energy balance partly via the regulation of adrenal steroid production.

KW - steroidogenesis

KW - MAPK

KW - AMPK

KW - adiponectin

KW - cortisol

KW - StAR

UR - http://www.scopus.com/inward/record.url?scp=79955690235&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2011.02.010

DO - 10.1016/j.bbamcr.2011.02.010

M3 - Article

VL - 1813

SP - 802

EP - 809

JO - BBA - Molecular Cell Research

JF - BBA - Molecular Cell Research

SN - 0167-4889

IS - 5

ER -