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Growth hormone STAT5-mediated signaling and its modulation in mice liver during the growth period.
- Source :
-
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society [Growth Horm IGF Res] 2013 Feb-Apr; Vol. 23 (1-2), pp. 19-28. Date of Electronic Publication: 2012 Dec 11. - Publication Year :
- 2013
-
Abstract
- Postnatal growth exhibits two instances of rapid growth in mice: the first is perinatal and independent of growth hormone (GH), the second is peripuberal and GH-dependent. Signal transducer and activator of transcription 5b (STAT5b) is the main GH-signaling mediator and it is related to IGF1 synthesis and somatic growth. The aim of this work was to assess differential STAT5 sensitivity to GH during the growth period in mouse liver of both sexes. Three representative ages were selected: 1-week-old animals, in the GH-independent phase of growth; 2.5-week-old mice, at the onset of the GH-dependent phase of growth; and 9-week-old young adults. GH-signaling mediators were assessed by immunoblotting, quantitative RT-PCR and immunohistochemistry. GH-induced STAT5 phosphorylation is low at one-week and maximal at 2.5-weeks of age when compared to young adults, accompanied by higher protein content at the onset of growth. Suppressor CIS and phosphatase PTP1B exhibit high levels in one-week animals, which gradually decline, while SOCS2 and SOCS3 display higher levels at adulthood. Nuclear phosphorylated STAT5 is low in one-week animals while in 2.5-week animals it is similar to 9-week control; expression of SOCS3, an early response GH-target gene, mimics this pattern. STAT5 coactivators glucocorticoid receptor (GR) and hepatic nuclear factor 1 (HNF1) abundance is higher in adulthood. Therefore, GH-induced STAT5 signaling presents age-dependent activity in liver, with its maximum coinciding with the onset of GH-dependent phase of growth, accompanied by an age-dependent variation of modulating factors. This work contributes to elucidate the molecular mechanisms implicated in GH responsiveness during growth.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Age Factors
Animals
Cell Nucleus drug effects
Cell Nucleus genetics
Cell Nucleus metabolism
Female
Growth Hormone pharmacology
Janus Kinase 2 metabolism
Liver drug effects
Male
Mice
Phosphorylation drug effects
Receptors, Somatotropin genetics
Receptors, Somatotropin metabolism
Signal Transduction drug effects
Signal Transduction physiology
Growth Hormone metabolism
Growth and Development drug effects
Growth and Development genetics
Growth and Development physiology
Liver growth & development
Liver metabolism
STAT5 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1532-2238
- Volume :
- 23
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
- Publication Type :
- Academic Journal
- Accession number :
- 23245546
- Full Text :
- https://doi.org/10.1016/j.ghir.2012.11.002