title: Prostaglandin F2-alpha receptor regulation in human uterine myocytes.
abstract: Investigations of the modulation of prostaglandin F(2alpha) receptor (FP) expression in primary cultures of human uterine myocytes showed that FP mRNA expression was reduced by progesterone, unaltered by cAMP (8-bromo cAMP or forskolin), but increased by the PKA antagonist H89. Interleukin (IL)-1beta, tumour necrosis factor-alpha and oxytocin increased FP mRNA expression and IL-6 and prostaglandin E(2) reduced FP mRNA expression. The changes in FP protein levels were similar to the mRNA responses. We found that the IL-1beta-induced increase in FP expression was mediated at least in part via protein kinase C (PKC), but was independent of mitogen-activated protein kinase, phospholipase C and PI3 kinase. Since IL-1beta activates NFkappaB, AP-1 and C/EBP, we over-expressed these transcription factors alone and in combination and found that only NFkappaB alone increased FP mRNA expression. Finally, we found that the IL-1beta-induced increase in FP expression was unaffected by progesterone and/or cAMP, but was accentuated by H89. These data suggest that the pregnancy-induced down-regulation in myometrial FP expression is mediated by progesterone and cAMP and that the increase with labour is induced by inflammatory cytokine activation of PKC and NFkappaB.
authors.affiliation: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 430038, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liang
authors.forename: S R
authors.initials: SR
authors.lastname: Sooranna
authors.forename: N
authors.initials: N
authors.lastname: Engineer
authors.forename: M
authors.initials: M
authors.lastname: Tattersall
authors.forename: S
authors.initials: S
authors.lastname: Khanjani
authors.forename: P R
authors.initials: PR
authors.lastname: Bennett
authors.forename: L
authors.initials: L
authors.lastname: Myatt
authors.forename: M R
authors.initials: MR
authors.lastname: Johnson
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008525:Medroxyprogesterone / Q000494:pharmacology; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014599:Uterus / Q000166:cytology*
chemical_list: D053583:Interleukin-1beta; D007546:Isoquinolines; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C034671:prostaglandin F2alpha receptor; D005576:Colforsin; D011374:Progesterone; D000242:Cyclic AMP; D008525:Medroxyprogesterone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide