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Mech Ageing Dev. 2015 Sep;150:74-82. doi: 10.1016/j.mad.2015.08.007. Epub 2015 Aug 21.

Up-regulation of steroid biosynthesis by retinoid signaling: Implications for aging.

Author information

1
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address: pulak.manna@ttuhsc.edu.
2
Dermatology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
3
Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
4
Physiologie de l'Axe Gonadotrope, INSERM U1133, F-75013 Paris, France.
5
Physiologie de l'Axe Gonadotrope, INSERM U1133, F-75013 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS, UMR 8251, F-75013 Paris, France.
6
Institute of Reproductive and Developmental Biology, Hammersmith Campus, Imperial College London, London W12 0NN, UK.
7
Department of Dermatology, University of Alabama at Birmingham, VA Medical Center at Birmingham, Birmingham, AL.
8
Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
9
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Abstract

Retinoids (vitamin A and its derivatives) are critical for a spectrum of developmental and physiological processes, in which steroid hormones also play indispensable roles. The StAR protein predominantly regulates steroid biosynthesis in steroidogenic tissues. We have reported that regulation of retinoid, especially atRA and 9-cis RA, responsive StAR transcription is largely mediated by an LXR-RXR/RAR heterodimeric motif in the mouse StAR promoter. Herein we demonstrate that retinoids are capable of enhancing StAR protein, P-StAR, and steroid production in granulosa, adrenocortical, glial, and epidermal cells. Whereas transient expression of RARα and RXRα enhanced 9-cis RA induced StAR gene transcription, silencing of RXRα with siRNA, decreased StAR and steroid levels. An oligonucleotide probe encompassing an LXR-RXR/RAR motif bound to adrenocortical and epidermal keratinocyte nuclear proteins in EMSAs. ChIP studies revealed association of RARα and RXRα with the StAR proximal promoter. Further studies demonstrated that StAR mRNA levels decreased in diseased and elderly men and women skin tissues and that atRA could restore steroidogenesis in epidermal keratinocytes of aged individuals. These findings provide novel insights into the relevance of retinoid signaling in the up-regulation of steroid biosynthesis in various target tissues, and indicate that retinoid therapy may have important implications in age-related complications and diseases.

KEYWORDS:

RAR; RXR; Retinoids; StAR expression; Steroid biosynthesis; Steroidogenic cells; cAMP/PKA

PMID:
26303142
PMCID:
PMC4583817
DOI:
10.1016/j.mad.2015.08.007
[Indexed for MEDLINE]
Free PMC Article

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