Developmental changes in the human growth hormone receptor and its signal transduction pathways

Although tissue human growth hormone receptors (GHRs) have been identified from as early as the first trimester of fetal life, little is known about their functional role. We recently reported that fetal hGHRs appear to be relatively immature or have adapted to the in utero environment [194]. To further characterize these age-related differences, we have examined certain aspects of the hGHR structure as well as its signalling pathways. Initial cDNA sequencing and immunoblotting analyses showed no difference in hGHR molecular size. We then used RT-PCR to investigate levels of an alternatively spliced mRNA for a truncated (1--279) hGHR (T) which acts as a dominant negative to the full-length (FL) receptor; however, fetal hepatocytes showed T/FL ratios similar to postnatal liver (0.07 +/- 0.02 vs. 0.09 +/- 0.01, M +/- SEM). Western blotting was used to assess developmental differences in the relative abundance of downstream signalling factors. Stimulatory Jak and Stat proteins were detected in all fetal hepatocytes and postnatal livers tested (13 weeks fetal age to 62 years). (Abstract shortened by UMI.