Growth hormone regulation of SOCS-2, SOCS-3, and CIS messenger ribonucleic acid expression in the rat.
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.
Tollet-Egnell
P
P
Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. petra.tollet.egnell@molmed.ki.se
Flores-Morales
A
A
Stavréus-Evers
A
A
Sahlin
L
L
Norstedt
G
G
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
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