Expression of Growth Hormone Receptor Isoform Exon-3-Excluding and Exon-3-Retaining Messenger RNAs in Peripheral Lymphocytes from Normal and Acromegalic Subjects

Abstract

Aim: To determine the expression of two isoforms of the growth hormone (GH) receptor (GHR), which differ by the presence (GHR3+) or absence (GHR3–) of exon 3, and their correlation with circulating GH and insulin-like growth factor I (IGF-I) in normal subjects and in acromegalic patients. Methods: The expression of GHR isoforms was determined by reverse-transcriptase polymerase chain reaction in lymphocytes from 12 normal subjects and from 11 patients with acromegaly. The levels of GHR mRNA were normalized to those of β-actin, and ratios were calculated to assess the relative levels of expression. Results: All samples showed expression of both GHR isoforms, but the expression of GHR3+ and GHR3– was similar in acromegalic patients (6.0 ± 1.7 vs. 8.3 ± 2.0%, mean ± SE). In contrast, in healthy subjects, GHR3– was the predominant isoform (11.8 ± 3.0 vs. 5.1 ± 0.68%; p < 0.05), and the levels of expression of GHR3– correlated significantly with IGF-I. Conclusions: These data demonstrate coexpression of both GHR isoforms under normal and pathological conditions; however, GHR3– is the predominant form in normal subjects and shows a negative correlation with IGF-I levels.

The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy

“…Microarray-based gene expression profiling has been successfully applied to the classification, outcome prediction and identification of genes and pathways deregulated in several human diseases. As GH receptors are expressed in certain blood cell types, [15][16][17] changes in gene expression in peripheral blood may reflect perturbations induced as a result of GH therapy and possibly serve as biomarkers of GH treatment. Characterization of suitable surrogate tissues will help to minimize these limitations.…”

“…As a result of its accessibility and ability to provide gene expression profiles, [12][13][14] peripheral blood may be the most feasible source of tissue. As GH receptors are expressed in certain blood cell types, [15][16][17] changes in gene expression in peripheral blood may reflect perturbations induced as a result of GH therapy and possibly serve as biomarkers of GH treatment. To test this hypothesis, we have assessed whether microarraybased gene expression profiling of peripheral blood mononuclear cells allows the identification of biomarkers of GH treatment in AGHD patients.…”

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone

“…The molecular mechanisms underlying the higher bioactivity of d3-GHR are not yet elucidated, but they do not seem to involve more binding [7][8][9] or less internalization 8 . In vivo, full-length GHR and d3-GHR isoforms might be discriminated at the level of expression in lymphocytes 12 . This is not the case in our assay, as both receptors are under the control of the constitutively active CMV promoter.…”