title: Induction of G protein-coupled estrogen receptor (GPER) and nuclear steroid hormone receptors by gonadotropins in human granulosa cells.
abstract: Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and estrogen receptor β (ERβ) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation. The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH. Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH and LH increased ERβ, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERβ and PR in luteinized granulosa cells.
authors.affiliation: Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University, Innenstadt, Maistrasse, Munich, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Pavlik
authors.forename: Gabriela
authors.initials: G
authors.lastname: Wypior
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hecht
authors.forename: Panos
authors.initials: P
authors.lastname: Papadopoulos
authors.forename: Markus
authors.initials: M
authors.lastname: Kupka
authors.forename: Christian
authors.initials: C
authors.lastname: Thaler
authors.forename: Irmi
authors.initials: I
authors.lastname: Wiest
authors.forename: Aurelia
authors.initials: A
authors.lastname: Pestka
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
mesh_terms: D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology* / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C109584:GPER1 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone