title: Differential regulation of suppressor of cytokine signaling-3 in the liver and adipose tissue of the sheep fetus in late gestation.
abstract: It is unknown whether the JAK/STAT/suppressor of cytokine signaling-3 (SOCS-3) intracellular signaling pathway plays a role in tissue growth and metabolism during fetal life. We investigated whether there is a differential profile of SOCS-3 expression in the liver and perirenal adipose tissue during the period of increased fetal growth in late gestation and the impact of fetal growth restriction on SOCS-3 expression in the fetal liver. We also determined whether basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is regulated by endogenous fetal prolactin (PRL). SOCS-3 mRNA abundance was higher in the liver than in the pancreas, spleen, and kidney of the sheep fetus during late gestation. In the liver, SOCS-3 mRNA expression was increased (P < 0.05) between 125 (n = 4) and 145 days (n = 7) gestation and lower (P < 0.05) in growth-restricted compared with normally grown fetal sheep in late gestation. The relative expression of SOCS-3 mRNA in the fetal liver was directly related to the mean plasma PRL concentrations during a 48-h infusion of either a dopaminergic agonist, bromocriptine (n = 7), or saline (n = 5), such that SOCS-3 mRNA expression was lower when plasma PRL concentrations decreased below approximately 20 ng/ml [y = 0.99 - (2.47/x) + (4.96/x(2)); r(2) = 0.91, P < 0.0001, n = 12]. No relationship was shown between the abundance of phospho-STAT5 in the fetal liver and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased (P < 0001) between 90-91 (n = 6) and 140-145 days (n = 9) gestation and was not related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed and regulated in key fetal tissues and may play an important and tissue-specific role in the regulation of cellular proliferation and differentiation before birth.
authors.affiliation: Centre for the Early Origins of Adult Health, Discipline of Physiology, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Sheridan
authors.initials: S
authors.lastname: Gentili
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Waters
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
mesh_terms: D000273:Adipose Tissue / Q000196:embryology* / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D010920:Placenta / Q000502:physiology; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012756:Sheep / Q000196:embryology*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C106644:SOCS3 protein, human; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D001971:Bromocriptine; D011388:Prolactin