[Role of the cytokine-3 signaling suppressor protein (SOCS 3) in growth hormone resistance induced by malnutrition].
Nutrition is an important regulator of growth hormone (GH) action. Nutritional deprivation causes a GH resistance involving post-receptor alterations in the signaling pathway, but the responsible mechanisms remain unknown. Herein, suppressors of cytokine signaling proteins (SOCS) were investigated as potential agents in GH-resistance induced by malnutrition which inhibits activation of Janus kinase 2/signal transductor and activator of transcription 5 (JAK2/STAT5) pathway. Growth hormone receptor (GHR), IGF-I and SOCS3 mRNA expression was measured in the liver of rats fed with a low protein diet and with GH stimulation. Protein diet restriction significantly diminished GHR mRNA and receptor binding sites (p < 0.05), but caused a highly increased SOCS3 gene expression. In diet-restricted rats, GH administration increased GHR and IGF-I mRNA; however, GHR reached basal levels observed in animals feeding with a high protein diet. The malnourished group increased SOCS3 gene transcription in response to GH administration. These results suggested that a reduced hepatic sensitivity to GH was associated with SOCS3 over-expression. In addition, ubiquitous distribution of SOCS3 and CIS suggests a role for SOCS proteins as tissue specific modulators of cytokine sensitivity.
Umaña
Adriana
A
Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, D.C., Colombia. yumana@ciencias.ciencias.unal.edu.co
Carrasco
Stella
S
Sánchez
Myriam
M
D000818:Animals; D005260:Female; D006130:Growth Disorders / Q000209:etiology*; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D044342:Malnutrition / Q000150:complications*; D011506:Proteins / Q000502:physiology*; 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; D014157:Transcription Factors
D011506:Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I