Developmental changes in the human GH receptor and its signal transduction pathways
Gurvinder Kenth1, Jennifer A Manalo Mergelas, Cynthia Gates Goodyer
1Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
The Journal of Endocrinology
|April 19, 2008
Summary
Functional human growth hormone receptors (hGHRs) are present in fetal liver, but lower levels of hGHR and signaling proteins like JAK2/STAT/SOCS explain limited fetal response to high hGH levels.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- Functional human growth hormone receptors (hGHRs) are present in first-trimester fetal hepatocytes (FH).
- Fetal serum hGH levels are high, yet hGH-dependent factors are expressed at low levels, suggesting limited fetal liver responsiveness.
- The reasons for this limited responsiveness, whether hGHR levels or signaling pathway factors, require investigation.
Purpose of the Study:
- To compare hGHR isoforms and downstream signaling proteins in fetal liver versus adult liver.
- To investigate the potential impact of hGHR levels and signaling components on fetal liver responsiveness to hGH.
Main Methods:
- Immunoprecipitation/immunoblotting (IB) to analyze hGHR forms and signaling proteins (JAK2, STATs, SOCS, CIS).
- Reverse transcription-polymerase chain reaction (RT-PCR) to assess truncated (T) vs. full-length (FL) hGHR mRNA ratios.
- Comparison of protein and mRNA levels between fetal hepatocytes (FH) and human adult liver (HAL).
Main Results:
- Similar precursor and mature hGHR forms were found in FH and HAL.
- T/FL hGHR mRNA ratios were comparable between FH and HAL.
- Levels of JAK2, STAT1, STAT3, and STAT5A were lower (38-53%) in FH compared to HAL, while STAT5B levels were similar.
- SOCS/CIS protein levels were significantly lower (58-76%) in FH compared to HAL.
- Overall hGHR levels were lower in fetal liver cells.
Conclusions:
- Hepatocyte development involves lower hGHR expression in fetal cells, with unchanged hGHR isoforms.
- Key signaling molecules (JAK2/STAT/SOCS) are present in early fetal liver but at reduced levels compared to adult liver.
- The diminished expression of both hGHR and major signaling components likely accounts for the limited responsiveness of fetal hepatocytes to high circulating hGH.
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