title: Induction of chemokines and prostaglandin synthesis pathways in luteinized human granulosa cells: potential role of luteotropin withdrawal and prostaglandin F2α in regression of the human corpus luteum.
abstract: Our objective was to determine the effects of prostaglandin F2α (PGF2α) and withdrawal of luteotropic stimulants (forskolin or hCG) on expression of chemokines and prostaglandin-endoperoxide synthase 2 (PTGS2) in luteinized human granulosa cells. Human granulosa cells were collected from 12 women undergoing oocyte retrieval and were luteinized in vitro with forskolin or hCG. In first experiment, granulosa-lutein cells were treated with PGF2α, the primary luteolytic hormone in most species. In second experiment, granulosa cells that had been luteinized for 8 d had luteotropins withdrawn for 1, 2, or 3 d. Treatment with PGF2α induced mRNA for chemokine (c-x-c motif) ligand 2 (CXCL2) and CXC ligand 8 (CXCL8; also known as interleukin-8) in granulosa cells luteinized for 8 d but not in cells that were only luteinized for 2 d. Similarly, luteinization of human granulosa cells for 8 d with forskolin or hCG followed by withdrawal of luteotropic stimulants, not only decreased P4 production, but also increased mRNA concentrations for CXCL8, CXCL-2 (after forskolin withdrawal), and PTGS2. These results provide evidence for two key steps in differentiation of luteolytic capability in human granulosa cells. During 8 d of luteinization, granulosa cells acquire the ability to respond to luteolytic factors, such as PGF2α, with induction of genes involved in immune function and PG synthesis. Finally, a decline in luteotropic stimuli triggers similar pathways leading to induction of PTGS2 and possibly intraluteal PGF2α production, chemokine expression, leukocyte infiltration and activation, and ultimately luteal regression.
authors.affiliation: Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States; Endocrinology-Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI, United States.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Luo
authors.affiliation: Endocrinology-Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI, United States; Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI, United States.
authors.forename: Sana M
authors.initials: SM
authors.lastname: Salih
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bormann
authors.affiliation: Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States; Endocrinology-Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI, United States. Electronic address: wiltbank@wisc.edu.
authors.forename: Milo C
authors.initials: MC
authors.lastname: Wiltbank
mesh_terms: D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003338:Corpus Luteum / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D003341:Luteolysis / Q000502:physiology*; D010908:Pituitary Hormones, Anterior / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C499706:CXCL2 protein, human; C508606:CXCL8 protein, human; D054426:Chemokine CXCL2; D018925:Chemokines; D006063:Chorionic Gonadotropin; D016209:Interleukin-8; D010908:Pituitary Hormones, Anterior; D011453:Prostaglandins; D012333:RNA, Messenger; D005576:Colforsin; D011374:Progesterone; C045090:luteotropin, decidual; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Chemokines; Luteinized granulosa cells; Luteolysis; PGF(2α); PTGS2