title: Growth hormone regulation of SOCS-2, SOCS-3, and CIS messenger ribonucleic acid expression in the rat.
abstract: The SOCS (suppressors of cytokine signaling) proteins have been suggested to function as inhibitors of cytokine receptor signaling. We have analyzed SOCS-2, SOCS-3, and CIS expression in relation to GH actions in the rat. SOCS-2, SOCS-3, and CIS transcripts were detected in various GH responsive tissues, including liver, muscle, and fat. In addition to the finding that different tissues express different levels of SOCS-2, SOCS-3, and CIS messenger RNA (mRNA), the steady-state levels of these SOCS transcripts were dependent on the endocrine status of the animal. SOCS-3 expression was 5-fold higher in fat from old compared with younger rats. Hypophysectomy reduced the levels of SOCS-2 and CIS mRNA in liver, muscle, and fat, whereas SOCS-3 expression was unchanged. Using primary cultures of rat hepatocytes, GH was shown to increase SOCS-2, SOCS-3, and CIS mRNA levels with different kinetics. SOCS-3 was rapidly and transiently induced, whereas SOCS-2 and CIS were increased in a slower fashion. Glucocorticoids blocked GH-induced SOCS-3 expression in cultured hepatocytes, whereas SOCS-2 and CIS expression was potentiated. Our data fit well with a concept of SOCS proteins acting as modulators of GH signal transduction.
authors.affiliation: Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. petra.tollet.egnell@molmed.ki.se
authors.forename: P
authors.initials: P
authors.lastname: Tollet-Egnell
authors.forename: A
authors.initials: A
authors.lastname: Flores-Morales
authors.forename: A
authors.initials: A
authors.lastname: Stavréus-Evers
authors.forename: L
authors.initials: L
authors.lastname: Sahlin
authors.forename: G
authors.initials: G
authors.lastname: Norstedt
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000172:deficiency / Q000502:physiology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007016:Hypophysectomy; D017874:Immediate-Early Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D018909:src Homology Domains
chemical_list: D004268:DNA-Binding Proteins; D003907:Dexamethasone; D013006:Growth Hormone; D019382:Human Growth Hormone; D017874:Immediate-Early Proteins; D007334:Insulin-Like Growth Factor I; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; C491408:Socs2 protein, rat; C491410:Socs3 protein, rat