Growth hormone-binding protein (GHBP) is complexed to a substantial fraction of circulating GH. In humans, rabbits, and other species, GHBP derives from proteolytic shedding of the GH receptor (GHR) extracellular domain. In cell culture studies, stimuli such as phorbol ester, platelet-derived growth factor, or serum induce GHR proteolysis, which concomitantly yields shed GHBP in cell supernatan...

A missense mutation, C422F, was identified in the intracellular domain of GH receptor (GHR) in a Japanese short boy. Although this mutation was previously reported in a patient with GH insensitivity syndrome (GHIS), it has not been clear whether this mutation causes GH insensitivity. To clarify the effect of this mutation on GH signal transduction, mutant GHR was expressed in CHO cells, and its...

Growth hormone receptor gene-disrupted (GHR-/-) mice exhibit increased life span and adipose tissue mass. Although this obese phenotype has been reported extensively for young adult male GHR-/- mice, data for females and for other ages in either gender are lacking. Thus, the purpose of this study was to evaluate body composition longitudinally in both male and female GHR-/- mice. Results show t...

Excessive GHRH stimulation leads to somatotrope hyperplasia and, ultimately, pituitary adenoma formation in the metallothionein promoter-driven human GHRH (hGHRH) transgenic mouse. This pituitary phenotype is similar to that observed in humans with ectopic production of GHRH. In both mice and man, GHRH hyperstimulation also results in dramatic increases in circulating GH and IGF-I. To determine...

Growth hormone (GH) regulates numerous cellular functions in many different tissues. A common receptor is believed to mediate these tissue-specific effects, suggesting that post-receptor signalling molecules or tissue sensitivity to GH may differ between tissues. Tissue sensitivity depends upon the abundance of GH receptors (GHRs), thus tissue-specific GHR regulation could enable tissue-specifi...

BACKGROUND Ghrelin has a protective effect on endothelial cells. Endothelial cell dysfunction is associated with cardiovascular disease (CVD) and CVD remains the leading cause of morbidity in hemodialysis (HD) patients. Acylated ghrelin (A-Ghr) is the functional form of ghrelin, so we hypothesized that A-Ghr is associated with the occurrence of CVD in HD patients. METHODS We conducted a prosp...

Growth hormone insensitivity syndrome (GHIS) has been reported in a family homozygous for a point mutation in the GH receptor (GHR) that activates an intronic pseudoexon. The resultant GHR (GHR1-656) includes a 36 amino-acids insertion after residue 207, in the region known to be important for homodimerization of GHR. We have examined the functional consequences of such an insertion in mammalia...

AIMS AND BACKGROUND Recombinant human growth hormone (rhGH) is increasingly used in the clinic because it promotes the synthesis of proteins. However, rhGH is able to increase malignant transformation and tumor recurrence. The aim of this study was to investigate the effects of rhGH on hepatocellular carcinoma (HCC) cells with positive and negative growth hormone receptors (GHR) in order to gui...

To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 +/- 2 vs. 20 +/- 4 mGU/ml, P < 0.05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P < 0.05) accompanied by a 25% reduct...

Ghrelin (GHR) is an orexigenic gut peptide that modulates multiple homeostatic functions including gastric emptying, anxiety, stress, memory, feeding, and reinforcement. GHR is known to bind and activate growth-hormone secretagogue receptors (termed GHR-Rs). Of interest to our laboratory has been the assessment of the impact of GHR modulation of the locomotor activation and reward/reinforcement...