title: Up-regulation of steroid biosynthesis by retinoid signaling: Implications for aging.
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.
authors: 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.
authors: Pulak R
authors: PR
authors: Manna
authors: Dermatology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors: Cloyce L
authors: CL
authors: Stetson
authors: Dermatology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors: Carol
authors: C
authors: Daugherty
authors: Dermatology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors: Ikue
authors: I
authors: Shimizu
authors: Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors: Peter J
authors: PJ
authors: Syapin
authors: Physiologie de l'Axe Gonadotrope, INSERM U1133, F-75013 Paris, France.
authors: Ghislaine
authors: G
authors: Garrel
authors: 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.
authors: Joelle
authors: J
authors: Cohen-Tannoudji
authors: Institute of Reproductive and Developmental Biology, Hammersmith Campus, Imperial College London, London W12 0NN, UK.
authors: Ilpo
authors: I
authors: Huhtaniemi
authors: Department of Dermatology, University of Alabama at Birmingham, VA Medical Center at Birmingham, Birmingham, AL.
authors: Andrzej T
authors: AT
authors: Slominski
authors: Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors: Kevin
authors: K
authors: Pruitt
authors: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors: Douglas M
authors: DM
authors: Stocco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009928:Organ Specificity; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D015595:Skin Aging; D013256:Steroids / Q000096:biosynthesis*; D015854:Up-Regulation; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D014801:Vitamin A
keywords: RAR; RXR; Retinoids; StAR expression; Steroid biosynthesis; Steroidogenic cells; cAMP/PKA