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This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/E600    most recent 00085.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Miquet, J. G. Articles by Turyn, D. Search for Related Content PubMed PubMed Citation Articles by Miquet, J. G. Articles by Turyn, D.

Desensitization of the JAK2/STAT5 GH signaling pathway associated with increased CIS protein content in liver of pregnant mice

¹Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológicas [University of Buenos Aires- Consejo Nacional de Investigaciones Cientificar y Techicas (CONICET)], Buenos Aires, Argentina; and ²Geriatrics Research, Departments of Internal Medicine and Physiology, School of Medicine, Southern Illinois University, Springfield, Illinois

Submitted 25 February 2005 ; accepted in final form 1 May 2005

Chronic exposure to growth hormone (GH) was related to the desensitization of the JAK2/STAT5 signaling pathway in liver, as demonstrated in cells, female rats, and transgenic mice overexpressing GH. The cytokine-induced suppressor (CIS) is considered a major mediator of this desensitization. Pregnancy is accompanied by an increment in GH circulating levels, which were reported to be associated with hepatic GH resistance, although the molecular mechanisms involved in this resistance are not clearly elucidated. We thus evaluated the JAK2/STAT5b signaling pathway and its regulation by the suppressors of cytokine signaling (SOCS)/CIS family and the JAK2-interacting protein SH2-B in pregnant mouse liver, a model with physiological prolonged exposure to high GH levels. Basal tyrosyl phosphorylation levels of JAK2 and STAT5b in pregnant mice were similar to values obtained for virgin animals, in spite of the important increment of GH they exhibit. Moreover, these signaling mediators were not phosphorylated upon GH stimulation in pregnant mice. A 3.3-fold increase of CIS protein content was found for pregnant mice, whereas the abundance of the other SOCS proteins analyzed and SH2-B did not significantly change compared with virgin animals. The desensitization of the JAK2/STAT5b GH signaling pathway observed in pregnant mice would then be mainly related to increased CIS levels rather than to the other regulatory proteins examined.

pregnant mice; growth hormone signaling; growth hormone receptor; suppressors of cytokine signaling/cytokine induced suppressors; signal transducer and activator of transcription