Ghrelin and growth hormone (GH) secretagogue receptor (GHSR) mRNA expression in human pituitary adenomas

Kim, Kyongsong; Arai, Keiko; Sanno, Naoko; Osamura, R. Yoshiyuki; Teramoto, Akira; Shibasaki, Tamotsu

doi:10.1046/j.1365-2265.2001.01286.x

Cited by 58 publications

(59 citation statements)

References 39 publications

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“…Our finding may link circulating or locally produced ghrelin to pituitary tumorigenesis via an autocrine/paracrine pathway. Indeed, ghrelin mRNA is expressed in pituitary tumours with the highest levels in non-functioning pituitary adenomas; however, the level of ghrelin mRNA expression did not correlate with tumour size or with the grading of the tumours (17,23). It has been demonstrated that GHS-R1a mRNA expression is increased in some somatotroph tumours, suggesting that the receptor may be a promoting factor in tumorigenesis (17,24).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway

Nanzer

Khalaf

Mozid

et al. 2004

European Journal of Endocrinology

126

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Objectives: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities and a widespread tissue distribution. Ghrelin is the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a), and both ghrelin and the GHS-R1a are expressed in the pituitary. There are conflicting data regarding the effects of ghrelin on cell proliferation. A positive effect on proliferation and activation of the mitogen-activated protein kinase (MAPK) pathway has been found in hepatoma, adipose, cardiomyocyte and prostate cell lines. However, ghrelin has also been shown to have antiproliferative effects on breast, lung and thyroid cell lines. We therefore examined the effect of ghrelin on the rat pituitary cell line GH3. Methods: RT-PCR was used for the detection of GHS-R1a and pre-proghrelin mRNA expression in GH3 cells. The effect of ghrelin on cell proliferation was studied using [ 3 H]thymidine incorporation; cell counting and the activation of the MAPK pathway were studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1/2), protein kinase C (PKC) and tyrosine phosphatase pathways. Results: GHS-R1a and ghrelin mRNA expression were detected in GH3 cells. Ghrelin 29 M compared with control), as well as on the cell count (control 6.8 £ 10 4^8 .7 £ 10 3 cells/ml vs desoctanoyl ghrelin (10 29 M) 1.04 £ 10 5^7 .5 £ 10 3 cells/ml; P , 0.01). Ghrelin caused a significant increase in phosphorylated ERK 1/2 in immunoblotting, while desoctanoyl ghrelin showed a smaller but also significant stimulatory effect. The positive effect of ghrelin and desoctanoyl ghrelin on [ 3 H]thymidine incorporation was abolished by the MAPK kinase inhibitor U0126, the PKC inhibitor GF109203X and the tyrosine kinase inhibitor tyrphostin 23, suggesting that the ghrelin-induced cell proliferation of GH3 cells is mediated both via a PKC-MAPK-dependent pathway and via a tyrosine kinase-dependent pathway. This could also be clearly demonstrated by Western blot analysis, where a transient increase in ERK 1/2 phosphorylation by ghrelin was attenuated by all three inhibitors. Conclusion: We have shown a novel role for ghrelin in stimulating the proliferation of a somatotroph pituitary tumour cell line, suggesting that ERK activation is involved in mediating the effects of ghrelin on cell proliferation. Desoctanoyl ghrelin showed a similar effect. As ghrelin has been shown to be expressed in both normal and adenomatous pituitary tissue, locally produced ghrelin may play a role in pituitary tumorigenesis via an autocrine/paracrine pathway.European Journal of Endocrinology 151 233-240

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Section: Discussionmentioning

confidence: 99%

Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway

Nanzer

Khalaf

Mozid

et al. 2004

European Journal of Endocrinology

126

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“…Two of 13 pediatric cases studied by RT-PCR contained the specific GHS-R 1a mRNA and approximately half of the cases had that of GHS-R 1b. Far from having demonstrated a direct (possibly autocrine or paracrine) mechanism of ghrelin in lung cells, the presence of the specific receptor in at least a fraction of cases may indicate that ghrelin not only regulates GH release at the central level but may also exert other functions in peripheral tissues via specific receptors, as also shown in the gastroenteropancreatic tract Volante et al 2002) and in pituitary adenomas (Kim et al 2001;Korbonits et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Ghrelin has subsequently been localized in the pituitary gland, arcuate nucleus of the hypothalamus, kidney, and placenta (Kojima et al 1999;Date et al 2000;Mori et al 2000;Gualillo et al 2001). Some tumors were also found to produce ghrelin, i.e., pituitary adenomas, gastrointestinal carcinoids, and endocrine tumors of the pancreas (Kim et al 2001;Korbonits et al 2001;Papotti et al 2001;Volante et al 2002).…”

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confidence: 99%

Ghrelin Expression in Fetal, Infant, and Adult Human Lung

Volante

Fulcheri²,

Allìa

et al. 2002

J Histochem Cytochem.

130

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S U M M A R YGhrelin is a recently identified hormone with potent growth hormone (GH)-releasing activity. It is produced by rat and human gastric endocrine cells and by the pituitary, hypothalamus, placenta, and by gastroenteropancreatic tumors. No evidence of ghrelin production by foregut-derived organs other than stomach has been provided to date. The aim of the present study was to investigate ghrelin expression by human fetal (20 cases), infant (13 cases), and adult (seven cases) lungs by immunohistochemistry, in situ hybridization, and RT-PCR. Expression of the GH secretagogue receptor, the endogenous receptor for ghrelin, was also investigated by RT-PCR. Ghrelin protein was found in the endocrine cells of the fetal lung in decreasing amounts from embryonic to late fetal periods. Its expression was maintained in newborns and children under 2 years but was virtually absent in older individuals. Scattered positive cells were also found in the trachea and the esophagus. Ghrelin mRNA was detected in adult lung by the more sensitive RT-PCR technique. GHS receptor mRNA was detected in nine cases of infant and adult lungs, possibly indicating the existence of local autocrine circuits. We conclude that the fetal lung is an additional source of circulating ghrelin, whose functions at the respiratory tract level remain to be clarified. (J Histochem

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“…Previous studies investigating ghrelin and GHSR expression in pituitary adenomas have produced conflicting results (3,6,8), and data showing the correlation between ghrelin and GHSR expression levels and the clinical features of pituitary adenomas are limited. The aim of the present study, therefore, was to examine the mRNA and protein expression levels of ghrelin and GHSR in a full spectrum of human pituitary adenoma subtypes, as well as normal pituitary tissue, and…”

Section: Introductionmentioning

confidence: 97%

“…Human GHSR contains two subtypes, type 1a (GHSR-1a) and type 1b (GHSR-1b), with the latter being 77 amino acids shorter than the former. Generally, GHRS-1a binds and responds to GHS, while GHRS-1b is biologically inactive (3).…”

Section: Introductionmentioning

confidence: 99%

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas

Wang

Guo

Han

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Ghrelin, as a brain-gut peptide, has growth hormone (GH)-releasing and appetite-inducing activities and a widespread tissue distribution. Furthermore, ghrelin is an endogenous ligand of the GH secretagogue receptor (GHSR), and both ghrelin and GHSR are expressed in the pituitary; however, the data regarding the expression of ghrelin and GHSR in pituitary adenomas are divergent and conflicting. In the present study, therefore, the expression of ghrelin and GHSR was examined in the full spectrum of human pituitary adenoma subtypes (n=34) and in normal pituitary tissue (n=3). The mRNA and protein expression levels were quantified using a competitive reverse transcription-polymerase chain reaction and western blotting and the correlation of the results with the clinical parameters was assessed. mRNA and protein expression of ghrelin and GHSR was detected in all samples with the highest mean level in GH adenomas, a moderate level in clinically non-functioning adenomas and the lowest level in adrenocorticotropin adenomas. A significant correlation between the ghrelin and GHSR mRNA expression levels was observed in the GH adenomas (n=12) (r=0.8435, P=0.0006). The ghrelin mRNA expression level in the GH adenomas correlated positively with the basic serum GH level (n=12) (r=0.6488, P=0.0225). Furthermore, the mean level of ghrelin mRNA expression was significantly higher in invasive adenomas than in noninvasive adenomas (P<0.01). Collectively, the results of the study provided evidence that ghrelin and GHSR are expressed in the various subtypes of pituitary adenoma, with specific overexpression in GH adenomas. The study suggests that the binding of ghrelin to GHSR promotes the secretion of GH and plays an important role in the development of GH adenomas via autocrine and/or paracrine effects.

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Ghrelin and growth hormone (GH) secretagogue receptor (GHSR) mRNA expression in human pituitary adenomas

Cited by 58 publications

References 39 publications

Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway

Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway

Ghrelin Expression in Fetal, Infant, and Adult Human Lung

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas

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