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Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha.

Publication ,  Journal Article
Grasfeder, LL; Gaillard, S; Hammes, SR; Ilkayeva, O; Newgard, CB; Hochberg, RB; Dwyer, MA; Chang, C-Y; McDonnell, DP
Published in: Mol Endocrinol
August 2009

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is involved in the coordinate induction of changes in gene expression in the liver that enable a homeostatic response to alterations in metabolic state, environmental cues, and nutrient availability. In exploring the specific pathways under PGC-1alpha regulation in the liver, we have made the surprising observation that this coactivator can induce the expression of CYP11A1 and CYP17A1, key rate-limiting enzymes involved in the initial steps of steroidogenesis. Both of these enzymes function to produce C(19)-steroids, converting cholesterol into pregnenolone, and then to dehydroepiandrosterone (DHEA). Estrogen-related receptor (ERR)-alpha mediates PGC-1alpha's induction of CYP11A1 and binds within the first intron of the CYP11A1 gene. Both ERR-alpha and hepatocyte nuclear factor-4alpha are required for PGC-1alpha-mediated induction of CYP17A1, and specific binding sites for these receptors have been identified in the regulatory regions of this gene. The potential physiological significance of these observations was highlighted in rats where fasting induced hepatic expression of PGC-1alpha and CYP17A1 and was associated with an increase in hepatic levels of DHEA. These data suggest that DHEA could be playing a role as an intracellular signaling molecule involved in modulating hepatic activity in response to fasting conditions.

Duke Scholars

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

August 2009

Volume

23

Issue

8

Start / End Page

1171 / 1182

Location

United States

Related Subject Headings

  • Transcription Factors
  • Steroids
  • Steroid 17-alpha-Hydroxylase
  • Signal Transduction
  • Receptors, Estrogen
  • Rats, Wistar
  • Rats
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Male
  • Liver
 

Citation

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MLA
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Grasfeder, L. L., Gaillard, S., Hammes, S. R., Ilkayeva, O., Newgard, C. B., Hochberg, R. B., … McDonnell, D. P. (2009). Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha. Mol Endocrinol, 23(8), 1171–1182. https://doi.org/10.1210/me.2009-0024
Grasfeder, Linda L., Stephanie Gaillard, Stephen R. Hammes, Olga Ilkayeva, Christopher B. Newgard, Richard B. Hochberg, Mary A. Dwyer, Ching-Yi Chang, and Donald P. McDonnell. “Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha.Mol Endocrinol 23, no. 8 (August 2009): 1171–82. https://doi.org/10.1210/me.2009-0024.
Grasfeder LL, Gaillard S, Hammes SR, Ilkayeva O, Newgard CB, Hochberg RB, et al. Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha. Mol Endocrinol. 2009 Aug;23(8):1171–82.
Grasfeder, Linda L., et al. “Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha.Mol Endocrinol, vol. 23, no. 8, Aug. 2009, pp. 1171–82. Pubmed, doi:10.1210/me.2009-0024.
Grasfeder LL, Gaillard S, Hammes SR, Ilkayeva O, Newgard CB, Hochberg RB, Dwyer MA, Chang C-Y, McDonnell DP. Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha. Mol Endocrinol. 2009 Aug;23(8):1171–1182.

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

August 2009

Volume

23

Issue

8

Start / End Page

1171 / 1182

Location

United States

Related Subject Headings

  • Transcription Factors
  • Steroids
  • Steroid 17-alpha-Hydroxylase
  • Signal Transduction
  • Receptors, Estrogen
  • Rats, Wistar
  • Rats
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Male
  • Liver