title: A prostaglandin f(2alpha) analog induces suppressors of cytokine signaling-3 expression in the corpus luteum of the pregnant rat: a potential new mechanism in luteolysis.
abstract: PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been shown to decrease cell sensitivity to cytokines, including PRL, and so here we have addressed the issue of whether luteolysis induced by prostaglandin F(2alpha) (PGF(2alpha)) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19 pregnant rats, cloprostenol, a PGF(2alpha) analog, rapidly induced transcripts for SOCS-3 and, to a lesser extent, SOCS-1. We also found increased SOCS-3 protein in the ovary by immunoblot and in the corpus luteum by immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was maintained for 4 h, as determined by gel shift and immunohistochemistry. Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF(2alpha) may be an important element in the initiation of luteolysis via rapid suppression of luteotropic support from PL.
authors.affiliation: School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, Australia. j.curlewis@mailbox.uq.edu.au
authors.forename: J D
authors.initials: JD
authors.lastname: Curlewis
authors.forename: S P
authors.initials: SP
authors.lastname: Tam
authors.forename: P
authors.initials: P
authors.lastname: Lau
authors.forename: D H L
authors.initials: DH
authors.lastname: Kusters
authors.forename: J L
authors.initials: JL
authors.lastname: Barclay
authors.forename: S T
authors.initials: ST
authors.lastname: Anderson
authors.forename: M J
authors.initials: MJ
authors.lastname: Waters
mesh_terms: D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000031:analogs & derivatives*; D015536:Down-Regulation; D005260:Female; D007267:Injections; D008894:Milk Proteins; D010053:Ovary / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011388:Prolactin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011981:Receptors, Prolactin / Q000502:physiology; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011506:Proteins; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011388:Prolactin; D015237:Dinoprost