Human growth hormone receptor gene expression is regulated by Gfi-1/1b and GAGA cis-elements.

Human growth hormone receptor (hGHR) gene regulation is complex: mRNAs are transcribed from multiple variant (V) 5'UTR exons, several ubiquitously while others only in the postnatal hepatocyte. The liver-specific V1 exon promoter contains Gfi-1/1b repressor sites adjacent to a GAGA box, a GH response element (GHRE) in several mammalian genes. GAGA boxes are also present in the ubiquitously expressing V3 exon promoter.

Developmental changes in the human GH receptor and its signal transduction pathways.

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).

Relationship of the human growth hormone receptor exon 3 genotype with final adult height and bone mineral density.

Context: Three recent clinical studies have reported that two of the most common isoforms of the human GH (hGH) receptor (hGHR), exon 3 full-length (3+) and exon 3 deleted (3-), may have differential effects on the growth response of children receiving hGH therapy, whereas others refute this. However, none of the investigations has explored the relationship between these hGHR isoforms and final adult height (FAH) or measures of bone mineral density (BMD) within a healthy adult population.

Objective: The aim of this study was to investigate the possible influences of hGHR exon 3 isoforms on FAH and BMD measures of a normal population.