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Developmental changes in the human GH receptor and its signal transduction pathways.
- Source :
-
The Journal of endocrinology [J Endocrinol] 2008 Jul; Vol. 198 (1), pp. 71-82. Date of Electronic Publication: 2008 Apr 17. - Publication Year :
- 2008
-
Abstract
- We previously reported the presence of functional human GH receptors (hGHRs) in the human fetal hepatocyte (FH) as early as the first trimester. Interestingly, fetal serum levels of hGH are in the acromegalic range, yet certain hGH-dependent factors are expressed at very low levels (IGF-I, IGF-binding protein-3), suggesting that fetal liver has limited responsiveness to hGH. To determine whether this is due to the fetal tissue levels of hGHR or factors in the hGH/hGHR axis that might influence hGHR function, we compared hGHR isoforms and downstream signaling proteins in FH versus human adult liver (HAL). Immunoprecipitation/immunoblotting (IB) analyses found similar precursor and mature hGHR forms while RT-PCR assays of truncated (T) hGHR(1-279), dominant negative for the full-length (FL) receptor, showed similar T/FL mRNA ratios in FH and HAL. IB demonstrated that Janus kinase (JAK) 2, signal transducers and activators of transcription (STAT(1, 3, 5A/B)), and suppressors of cytokine signaling (SOCS(1, 2, 3, cytokine-inducible SH2-containing protein (CIS))) proteins were detectable in all FH and HAL tested (12 weeks of fetal age to 60 years); the levels were similar (STAT5B) or lower (JAK2/STAT1/STAT3/STAT5A: 38-53%, SOCS/CIS: 58-76%) in FH compared with HAL. Our studies to date demonstrate that, during hepatocyte development, hGHR levels are lower in the fetal cells but the hGHR isoforms, including the relative amount of truncated versus FL, remain unchanged. The JAK2/STAT/SOCS signaling molecules are present in the FH as early as the first trimester. However, they are generally at <50% level in postnatal liver. These data suggest that low expression of both hGHR and major hGHR signaling components may explain the limited responsiveness of the fetal cells to the high circulating levels of hGH.
- Subjects :
- Animals
Cell Line
Hepatocytes chemistry
Humans
Janus Kinase 2 analysis
Janus Kinase 2 physiology
Liver chemistry
Membrane Proteins genetics
Membrane Proteins physiology
RNA, Messenger analysis
STAT Transcription Factors analysis
STAT Transcription Factors physiology
Suppressor of Cytokine Signaling Proteins analysis
Suppressor of Cytokine Signaling Proteins physiology
Fetus chemistry
Membrane Proteins analysis
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1479-6805
- Volume :
- 198
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 18420710
- Full Text :
- https://doi.org/10.1677/JOE-07-0648