title: Retinoids and retinol differentially regulate steroid biosynthesis in ovarian theca cells isolated from normal cycling women and women with polycystic ovary syndrome.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is characterized by ovarian androgen excess and infertility. Recent experiments have suggested that several genes involved in retinoic acid synthesis may be differentially expressed in PCOS theca cells and may contribute to excessive theca-derived androgen production.
  
  
  OBJECTIVE
  The study was performed to examine whether there are differential effects of retinol and retinoids on normal and PCOS theca cell function.
  
  
  METHODS
  We used in vitro assays.
  
  
  METHODS
  The study was conducted at the university laboratory.
  
  
  METHODS
  We studied theca interna cells isolated from normal-cycling women and women with PCOS.
  
  
  METHODS
  Theca cells were treated with all-trans-retinoic acid (atRA), 9-cis retinoic acid (9-cis RA), or the retinoic acid precursor retinol.
  
  
  METHODS
  We measured dehydroepiandrosterone, testosterone, and progesterone biosynthesis as well as cytochrome P450 17alpha-hydroxylase (CYP17), cytochrome P450 cholesterol side-chain cleavage, and steroidogenic acute regulatory protein mRNA abundance and promoter function.
  
  
  RESULTS
  Dehydroepiandrosterone production was increased by atRA and 9-cis RA in normal cells and by atRA, 9-cis RA, and retinol in PCOS. Testosterone production was increased by atRA in normal and by atRA, 9-cis RA, and retinol in PCOS. Progesterone production was not altered by retinoid treatment. Retinoids stimulated mRNA abundance and promoter function for CYP17 and steroidogenic acute regulatory protein in both cell types and cytochrome P450 cholesterol side-chain cleavage in normal cells. Retinol stimulated CYP17 mRNA accumulation and promoter function in PCOS but not normal theca cells. P < 0.05 was considered statistically significant.
  
  
  CONCLUSIONS
  Differential responses to retinol and retinoids in normal and PCOS theca suggest that altered retinoic acid synthesis and action may be involved in augmented CYP17 gene expression and androgen production in PCOS.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State Hershey College of Medicine, 500 University Drive, C4723, Hershey, Pennsylvania 17033, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Wickenheisser
authors.forename: Velen L
authors.initials: VL
authors.lastname: Nelson-DeGrave
authors.forename: Karen L
authors.initials: KL
authors.lastname: Hendricks
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
authors.forename: Jan M
authors.initials: JM
authors.lastname: McAllister
mesh_terms: D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000378:metabolism; D066298:In Vitro Techniques; D010750:Phosphoproteins / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis; D013799:Theca Cells / Q000187:drug effects* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000970:Antineoplastic Agents; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D014801:Vitamin A; D000077556:Alitretinoin; D013739:Testosterone; D003687:Dehydroepiandrosterone; D014212:Tretinoin; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme