title: Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor 30 (GPR30) in Mouse Corpus Luteum.
abstract: The corpus luteum (CL) is a transient endocrine gland developed from the ovulated follicles, and the most important function is to synthesize and secrete progesterone (P(4)), a key hormone to maintain normal pregnancy and estrous cycle in most mammals. It is known that estrogen has a vital role in stimulating P(4) synthesis in CL, but it still remains unclear about the mechanism of estradiol (E(2)) regulating P(4) production in CL. Our results here first show that all of the CL cells express MAPK 8 (MAP3K8), and the MAP3K8 level is much higher at the midstage than at the early and late stages during CL development. The further functional studies show that the forced inhibition of endogenous MAP3K8 by using MAP3K8 small interfering RNA and MAP3K8 signaling inhibitor (MAP3K8i) in the luteal cells significantly block the P(4) synthesis and neutralize the enhancing effect of E(2) on P(4) production in the CL. In addition, our results here demonstrate that the stimulating effect of E(2) on P(4) synthesis relies on the estrogen no-classical protein-coupled receptor 30, and MAP3K8 is involved in mediating the protein-coupled receptor 30signaling of E(2) affecting P(4) synthesis via stimulating ERK phosphorylation. These novel findings are critical for our understanding the ovary physiology and pathological mechanism.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Jiali
authors.initials: J
authors.lastname: Liu
authors.forename: Kemian
authors.initials: K
authors.lastname: Gou
authors.forename: Sheng
authors.initials: S
authors.lastname: Cui
mesh_terms: D000818:Animals; D003338:Corpus Luteum / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D010064:Embryo Implantation; D004958:Estradiol / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C532507:GPER1 protein, mouse; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D011374:Progesterone; D004958:Estradiol; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020930:MAP Kinase Kinase Kinases; C489843:Map3k8 protein, mouse