title: A positive feedback loop between progesterone and microsomal prostaglandin E synthase-1-mediated PGE2 promotes production of both in mouse granulosa cells.
abstract: Microsomal prostaglandin E synthase-1 (mPGES-1) is primarily expressed in granulosa cells (GCs) in the preovulatory follicle. Both prostaglandin E2 (PGE2) and progesterone (P4) are implicated in various reproductive functions. Here, we demonstrate that mPges-1 may be a direct downstream target gene of the P4 receptor and P4-stimulated PGE2 secretion can stimulate P4 production in a newly generated mouse GC line (GtsT). Treatment of GtsT cells with a P4 receptor agonist, norgestrel, markedly increased mPGES-1 expression detected by RT-PCR analysis. PGE2 secretion measured by an enzyme-linked immunosorbent assay was enhanced by P4 treatment. Luciferase assays revealed that the proximal promoter region of the mPges-1 gene was responsible for the effects of P4 treatment. Conversely, PGE2 treatment stimulated P4 secretion, which coordinated with mRNA expression of steroidogenic acute regulatory protein. Taken together, P4 may regulate mPGES-1 expression to increase PGE2 secretion and in turn P4 production. An autocrine loop between P4 and PGE2 might function to maintain the increased levels of both in GCs.
authors.affiliation: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: hiro@toyaku.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Department of Cell Biology and Molecular Pathology, Iwate Medical University, School of Pharmacy, 2-1-1 Nishitokuta, Yahaba, Shiwa, Iwate 028-3694, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Naraba
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagayaku, Tokyo 156-85-06, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Yoshie
authors.affiliation: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogo
authors.affiliation: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tachikawa
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D009644:Norgestrel / Q000494:pharmacology; D061251:Primary Cell Culture; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000071876:Prostaglandin-E Synthases / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D011980:Receptors, Progesterone; D009644:Norgestrel; D011374:Progesterone; D008156:Luciferases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate
keywords: Granulosa cell; Microsomal prostaglandin E synthase-1; Progesterone; Prostaglandin E2; Steroidogenic acute regulatory protein