title: Chemerin, a novel regulator of follicular steroidogenesis and its potential involvement in polycystic ovarian syndrome.
abstract: Polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome associated with follicle growth arrest, minimal granulosa cell proliferation, dysregulated sex hormone profile, hyperthecosis, and insulin resistance. Using a 5α-dihydrotestosterone (DHT)-induced rat model that recapitulates the reproductive and metabolic phenotypes of human PCOS, we have examined the steroidogenic capability of granulosa cells from DHT-treated rats. Gene expression of several key steroidogenic enzymes including p450 side-chain cleavage enzyme (p450scc), aromatase, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenase-17β, and hydroxysteroid dehydrogenase-3β were markedly lower in DHT-treated rats than the controls, although the responsiveness of their granulosa cells to FSH was higher. Expression of the adipokine chemerin and its receptor, chemokine receptor-like 1, was evident in control and DHT-treated rats, with significantly higher ovarian mRNA abundances and protein contents of chemerin and its receptor. Recombinant chemerin decreases basal estradiol secretion in granulosa cells from DHT-treated rats. When the inhibitory role of chemerin on steroidogenesis was further examined in vitro, chemerin suppressed FSH-induced progesterone and estradiol secretion in cultured preantral follicles and granulosa cells. Chemerin also inhibits FSH-induced aromatase and p450scc expression in granulosa cells. Overexpression of nuclear receptors NR5a1 and NR5a2 promotes p450scc and aromatase expression, respectively, which is suppressed by chemerin. These findings suggest that chemerin is a novel negative regulator of FSH-induced follicular steroidogenesis and may contribute to the pathogenesis of PCOS.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kai
authors.initials: K
authors.lastname: Xue
authors.forename: Jia-yin
authors.initials: JY
authors.lastname: Liu
authors.forename: Arthur
authors.initials: A
authors.lastname: Leader
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D018925:Chemokines; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D054392:Adipokines; D018925:Chemokines; D012739:Gonadal Steroid Hormones; D036341:Intercellular Signaling Peptides and Proteins; C560738:Rarres2 protein, rat; D019707:Receptors, Chemokine; D054339:Steroidogenic Factor 1; D013196:Dihydrotestosterone; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme