title: Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome.
abstract: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes including Cyp11a1, StAR, Cyp19a1, and 3β-HSD were upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3β-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS.
  
  
  BACKGROUND
  AMHR-II: anti-müllerian hormone receptor-II; 3β-HSD: 3β-hydroxysteroid dehydrogenase; Cyp11a1: Cytochrome P450 Family 11 Subfamily A Member 1; Cyp19a1: cytochrome P450 aromatase; DHEA: dehydroepiandrosterone; FSH: follicle stimulating hormone; FSHR: follicle stimulating hormone receptor; IVF: in vitro fertilization; 25OHD: 25-hydroxy vitamin D; OHSS: ovarian hyperstimulation syndrome; PCOS: polycystic ovarian syndrome; P450scc: P450 side-chain cleavage enzyme; StAR: steroidogenic acute regulatory protein; VDRs: vitamin D receptors.
authors.affiliation: a Department of Anatomy, School of medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Bakhshalizadeh
authors.affiliation: a Department of Anatomy, School of medicine , Tehran University of Medical Sciences , Tehran , Iran.|b Department of Infertility, Shariati Hospital , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Fardin
authors.initials: F
authors.lastname: Amidi
authors.affiliation: c Department of Obstetrics and Gynecology, Shariati Hospital , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Alleyassin
authors.affiliation: d Department of Hematology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: e Cellular and Molecular Research Center , Iran University of Medical Sciences , Tehran , Iran.|f Department of Anatomical Sciences, Faculty of Medicine , Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Shirazi
authors.affiliation: a Department of Anatomy, School of medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shabani Nashtaei
mesh_terms: D000818:Animals; D002762:Cholecalciferol / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D030762:Estrous Cycle; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis* / Q000097:blood; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology; D008807:Mice, Inbred BALB C; D010053:Ovary / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D012739:Gonadal Steroid Hormones; D002762:Cholecalciferol
keywords: Granulosa cells; hyperandrogenism; polycystic ovarian syndrome (PCOS); steroidogenic enzymes; vitamin D3