title: The role of GPR1 signaling in mice corpus luteum.
abstract: Chemerin, a chemokine, plays important roles in immune responses, inflammation, adipogenesis, and carbohydrate metabolism. Our recent research has shown that chemerin has an inhibitory effect on hormone secretion from the testis and ovary. However, whether G protein-coupled receptor 1 (GPR1), the active receptor for chemerin, regulates steroidogenesis and luteolysis in the corpus luteum is still unknown. In this study, we established a pregnant mare serum gonadotropin-human chorionic gonadotropin (PMSG-hCG) superovulation model, a prostaglandin F2α (PGF2α) luteolysis model, and follicle and corpus luteum culture models to analyze the role of chemerin signaling through GPR1 in the synthesis and secretion of gonadal hormones during follicular/luteal development and luteolysis. Our results, for the first time, show that chemerin and GPR1 are both differentially expressed in the ovary over the course of the estrous cycle, with highest levels in estrus and metestrus. GPR1 has been localized to granulosa cells, cumulus cells, and the corpus luteum by immunohistochemistry (IHC). In vitro, we found that chemerin suppresses hCG-induced progesterone production in cultured follicle and corpus luteum and that this effect is attenuated significantly by anti-GPR1 MAB treatment. Furthermore, when the phosphoinositide 3-kinase (PI3K) pathway was blocked, the attenuating effect of GPR1 MAB was abrogated. Interestingly, PGF2α induces luteolysis through activation of caspase-3, leading to a reduction in progesterone secretion. Treatment with GPR1 MAB blocked the PGF2α effect on caspase-3 expression and progesterone secretion. This study indicates that chemerin/GPR1 signaling directly or indirectly regulates progesterone synthesis and secretion during the processes of follicular development, corpus luteum formation, and PGF2α-induced luteolysis.
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Shenzhen Key Laboratory of Birth DefectsShenzhen Baoan Maternal and Child Health Hospital, Shenzhen, Guangdong, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Ren
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Sun
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China University of Chinese Academy of SciencesShenzhen, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Tian-Xia
authors.initials: TX
authors.lastname: Xiao
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Bao-Bei
authors.initials: BB
authors.lastname: Wang
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology and Vascular BiologyDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA, and Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Zabel
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China peigen.ren@siat.ac.cn jian.zhang@siat.ac.cn.
authors.forename: Peigen
authors.initials: P
authors.lastname: Ren
authors.affiliation: Research Laboratory for Reproductive HealthShenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China peigen.ren@siat.ac.cn jian.zhang@siat.ac.cn.
authors.forename: Jian V
authors.initials: JV
authors.lastname: Zhang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D003341:Luteolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013480:Superovulation / Q000502:physiology*
chemical_list: D018925:Chemokines; D006063:Chorionic Gonadotropin; C000591279:GPR1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse; D011374:Progesterone; D004958:Estradiol; D015237:Dinoprost; D019869:Phosphatidylinositol 3-Kinases; D053148:Caspase 3
keywords: GPR1; chemerin; corpus luteum; progesterone