Skip to main content
Top
Published in: Digestive Diseases and Sciences 4/2011

Open Access 01-04-2011 | Original Article

The Expression of PTHLH in Human Gastric Mucosa Enterochromaffin-Like Cells

Authors: Cuiping Liu, Jianting Chen, Yu Guo, Lisheng Yang, Chengyi Zhao, Lan Bai

Published in: Digestive Diseases and Sciences | Issue 4/2011

Login to get access

Abstract

Background

Gastrectomy may disturb the body’s mineral homeostasis, with osteopenia and osteoporosis being among the late outcomes. Parathyroid hormone-like hormone (PTHLH) was detected in rat gastric enterochromaffin-like (ECL) cells in 2005, and some researchers suggested that it was the hypothetical hormone gastrocalcin that is believed to lead to osteoporosis.

Aims

Our objective was to learn whether PTHLH is expressed in human gastric ECL cells and to form a basic understanding about the relationship between PTHLH and gastrin.

Methods

We collected normal human gastric mucosa specimens and serum samples from 28 patients.

Results

RT-PCR and immunohistochemical analysis demonstrated weak expression of PTHLH in ECL cells at the RNA and protein levels. A low level of PTHLH expression was also found in the serum. Serum gastrin did have a significant positive correlation with the relative ratio of PTHLH mRNA to β-actin levels in gastric mucosa (r s  = 0.569, p = 0.002).

Conclusions

This indicates that PTHLH has a low signal expression in human gastric ECL cells and that serum gastrin levels correlate with PTHLH RNA levels in gastric mucosa. Further work is needed to evaluate the functional role of PTHLH in ECL cells and to determine whether PTHLH is gastrocalcin.
Literature
1.
go back to reference Andersson N, Surve W, Lehto-Axtelius D, et al. Drug-induced prevention of gastrectomy-and ovariectomy-induced osteopaenia in the young female rat. J Endocrinol. 2002;175(3):695–703.PubMedCrossRef Andersson N, Surve W, Lehto-Axtelius D, et al. Drug-induced prevention of gastrectomy-and ovariectomy-induced osteopaenia in the young female rat. J Endocrinol. 2002;175(3):695–703.PubMedCrossRef
2.
go back to reference Persson P, Gaqnemo-Persson R, Chen D, et al. Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible? Scand J Gastroenterol. 1993;28(4):301–306.PubMedCrossRef Persson P, Gaqnemo-Persson R, Chen D, et al. Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible? Scand J Gastroenterol. 1993;28(4):301–306.PubMedCrossRef
3.
go back to reference Adachi Y, Shiota E, Matsumata T, et al. Bone mineral density in patients taking H2-receptor antagonist. Calcif Tissue Int. 1998;62(4):283–285.PubMedCrossRef Adachi Y, Shiota E, Matsumata T, et al. Bone mineral density in patients taking H2-receptor antagonist. Calcif Tissue Int. 1998;62(4):283–285.PubMedCrossRef
4.
go back to reference Klinge B, Lehto-Axtelius D, Akerman M, et al. Structure of calvaria after gastrectomy. An experimental study in the rat. J Clin Endocrinol. 1995;30(10):952–957. Klinge B, Lehto-Axtelius D, Akerman M, et al. Structure of calvaria after gastrectomy. An experimental study in the rat. J Clin Endocrinol. 1995;30(10):952–957.
5.
go back to reference Schmiedl A, Schwille PO, Stuhler C, et al. Low bone mineral density after total gastrectomy in males: a preliminary report emphasizing the possible significance of urinary net acid excretion, serum gastrin and phosphorus. Clin Chem Lab Med. 1999;37(7):739–744.PubMedCrossRef Schmiedl A, Schwille PO, Stuhler C, et al. Low bone mineral density after total gastrectomy in males: a preliminary report emphasizing the possible significance of urinary net acid excretion, serum gastrin and phosphorus. Clin Chem Lab Med. 1999;37(7):739–744.PubMedCrossRef
6.
go back to reference Davies M, Heys SE, Selby PL, et al. Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy, elevated 1, 25-dihydroxyvitamin D levels. Implications for metabolic bone disease. J Clin Endocrinol Metab. 1997;82(1):209–212.PubMedCrossRef Davies M, Heys SE, Selby PL, et al. Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy, elevated 1, 25-dihydroxyvitamin D levels. Implications for metabolic bone disease. J Clin Endocrinol Metab. 1997;82(1):209–212.PubMedCrossRef
7.
go back to reference Persson P, Häkanson R, Axelson J, et al. Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach. Proc Natl Acad Sci USA. 1989;86(8):2834–2838.PubMedCrossRef Persson P, Häkanson R, Axelson J, et al. Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach. Proc Natl Acad Sci USA. 1989;86(8):2834–2838.PubMedCrossRef
8.
go back to reference Larsson B, Gritli-Linde A, Norlen P, et al. Extracts of ECL-cell granules/vesicles, of isolated ECL cells from rat oxyntic mucosa evoke a Ca second messenger response in osteoblastic cells. Regul Pept. 2001;97(2–3):153–161.PubMedCrossRef Larsson B, Gritli-Linde A, Norlen P, et al. Extracts of ECL-cell granules/vesicles, of isolated ECL cells from rat oxyntic mucosa evoke a Ca second messenger response in osteoblastic cells. Regul Pept. 2001;97(2–3):153–161.PubMedCrossRef
9.
go back to reference Larsson B, Norlen P, Lindstrom E, et al. Effects of ECL cell extracts and granule/vesicle-enriched fractions from rat oxyntic mucosa on cAMP and IP3 in rat osteoblast-like cells. Regul Pept. 2002;106(1–3):13–18. Jun 15.PubMedCrossRef Larsson B, Norlen P, Lindstrom E, et al. Effects of ECL cell extracts and granule/vesicle-enriched fractions from rat oxyntic mucosa on cAMP and IP3 in rat osteoblast-like cells. Regul Pept. 2002;106(1–3):13–18. Jun 15.PubMedCrossRef
10.
go back to reference Burtis WJ, Wu T, Bunch C, et al. Identification of a novel 17,000-Dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem. 1987;262(15):7151–7156.PubMed Burtis WJ, Wu T, Bunch C, et al. Identification of a novel 17,000-Dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem. 1987;262(15):7151–7156.PubMed
11.
go back to reference Meyer R, Schreckenberg R, Kretschmer F, et al. Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart. Eur J Heart Fail. 2007;9(12):1156–1162.PubMedCrossRef Meyer R, Schreckenberg R, Kretschmer F, et al. Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart. Eur J Heart Fail. 2007;9(12):1156–1162.PubMedCrossRef
12.
go back to reference Sharpe GR, Dillon JP, Durham B, et al. Human keratinocytes express transcripts for three isoforms of parathyroid hormone-related protein(PTHrP), but not for the parathyroid hormone/PTHrP receptor: effects of 1, 25(OH)2 vitamin D3. British J Dermatology. 1998;138(6):944–951.CrossRef Sharpe GR, Dillon JP, Durham B, et al. Human keratinocytes express transcripts for three isoforms of parathyroid hormone-related protein(PTHrP), but not for the parathyroid hormone/PTHrP receptor: effects of 1, 25(OH)2 vitamin D3. British J Dermatology. 1998;138(6):944–951.CrossRef
13.
go back to reference Martin TJ. Osteoblast-derived PTHrP is a physiological regulator of bone formation. J Clin Invest. 2005;115(9):2322–2324.PubMedCrossRef Martin TJ. Osteoblast-derived PTHrP is a physiological regulator of bone formation. J Clin Invest. 2005;115(9):2322–2324.PubMedCrossRef
14.
go back to reference Andersson N, Skrtic SM, Hakanson R, et al. A gene expression fingerprint of mouse stomach ECL cells. Biochem Biophys Res Commun. 2005;332(2):404–410.PubMedCrossRef Andersson N, Skrtic SM, Hakanson R, et al. A gene expression fingerprint of mouse stomach ECL cells. Biochem Biophys Res Commun. 2005;332(2):404–410.PubMedCrossRef
15.
go back to reference Reppe S, Stilgren L, Abrahamsen B, et al. Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism. Am J Physiol Endocrinol Metab. 2007;292(5):E1465–E1473.PubMedCrossRef Reppe S, Stilgren L, Abrahamsen B, et al. Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism. Am J Physiol Endocrinol Metab. 2007;292(5):E1465–E1473.PubMedCrossRef
16.
go back to reference Tenne M, McGuigan F, Jansson L. Genetic variation in the PTH pathway, bone phenotypes in elderly women: evaluation of PTH, PTHLH, PTHR1, PTHR2 genes. Bone. 2008;42(4):719–727.PubMedCrossRef Tenne M, McGuigan F, Jansson L. Genetic variation in the PTH pathway, bone phenotypes in elderly women: evaluation of PTH, PTHLH, PTHR1, PTHR2 genes. Bone. 2008;42(4):719–727.PubMedCrossRef
17.
go back to reference Orloff JJ, Stewart AF. The carboxy-terminus of parathyroid hormone—inert or invaluable? Endocrinology. 1995;136:4729–4731.PubMedCrossRef Orloff JJ, Stewart AF. The carboxy-terminus of parathyroid hormone—inert or invaluable? Endocrinology. 1995;136:4729–4731.PubMedCrossRef
18.
go back to reference Torbergsen K, Wiksen H, Johansen K, et al. Immunoreactivity of gastric ECL, A-like cells infasted, fed rats, mice. Biotechnic Histochem. 2005;80(1):21–30.CrossRef Torbergsen K, Wiksen H, Johansen K, et al. Immunoreactivity of gastric ECL, A-like cells infasted, fed rats, mice. Biotechnic Histochem. 2005;80(1):21–30.CrossRef
19.
go back to reference Bjorkqvist M, Dornonville de la Cour C, Zhao CM, et al. Role of gastrin in the development of gastric mucosa, ECL cells, A-like cells in newborn, young rats. Reg Pept. 2002;108(2–3):73–82.CrossRef Bjorkqvist M, Dornonville de la Cour C, Zhao CM, et al. Role of gastrin in the development of gastric mucosa, ECL cells, A-like cells in newborn, young rats. Reg Pept. 2002;108(2–3):73–82.CrossRef
20.
go back to reference Kidd M, Modlin IM, Black JW, et al. A comparison of the effects of gastrin, somatostatin and dopamine receptor ligands on rat gastric enterochromaffin-like cell secretion and proliferation. Regulatory Peptides. 2007;143(1–3):109–117.PubMedCrossRef Kidd M, Modlin IM, Black JW, et al. A comparison of the effects of gastrin, somatostatin and dopamine receptor ligands on rat gastric enterochromaffin-like cell secretion and proliferation. Regulatory Peptides. 2007;143(1–3):109–117.PubMedCrossRef
21.
go back to reference Nishi T, Makuuchi H, Weinstein M, et al. Changes in gastric ECL cells, parietal cells after long-term administration of high-dose omeprazole to patients with Barrett’s esophagus. Tokai J Exp Clin Med. 2005;30(2):117–121.PubMed Nishi T, Makuuchi H, Weinstein M, et al. Changes in gastric ECL cells, parietal cells after long-term administration of high-dose omeprazole to patients with Barrett’s esophagus. Tokai J Exp Clin Med. 2005;30(2):117–121.PubMed
22.
go back to reference Lindstrom E, Chen D, Norlen P, et al. Control of gastric acid secretion: the gastrin-ECL cell-parietal cell axis. Comp Biochem Physiol A Mol Integr Physiol. 2001;128(3):505–514.PubMedCrossRef Lindstrom E, Chen D, Norlen P, et al. Control of gastric acid secretion: the gastrin-ECL cell-parietal cell axis. Comp Biochem Physiol A Mol Integr Physiol. 2001;128(3):505–514.PubMedCrossRef
23.
go back to reference Bjorkgvist M, Bernsand M, Eliasson L, et al. Somatostatin, misoprostol and galanin inhibit gastrin-and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca2+ channels. Regulatory Peptides. 2005;130(1–2):81–90.CrossRef Bjorkgvist M, Bernsand M, Eliasson L, et al. Somatostatin, misoprostol and galanin inhibit gastrin-and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca2+ channels. Regulatory Peptides. 2005;130(1–2):81–90.CrossRef
24.
go back to reference Rubin W, Schwartz B. Electron microscopic radioautographic identification of the ECL cell as the histamine-synthesizing endocrine cell in the rat stomach. Gastroenterology. 1979;77(3):458–467.PubMed Rubin W, Schwartz B. Electron microscopic radioautographic identification of the ECL cell as the histamine-synthesizing endocrine cell in the rat stomach. Gastroenterology. 1979;77(3):458–467.PubMed
25.
go back to reference Rosen CJ, Bilezikian JP. Clinical review 123: anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 2001;86(3):957–964.PubMedCrossRef Rosen CJ, Bilezikian JP. Clinical review 123: anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 2001;86(3):957–964.PubMedCrossRef
26.
go back to reference Horwitz MJ, Tedesco MB, Gundberg C, et al. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003;88(2):569–575.PubMedCrossRef Horwitz MJ, Tedesco MB, Gundberg C, et al. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003;88(2):569–575.PubMedCrossRef
27.
go back to reference Plotkin H, Gundberg C, Mitnick M, et al. Dissociation of bone formation from resorption during two-week treatment with human parathyroid hormone-related peptide-(1–36) in humans: potential as an anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 1998;83(8):2786–2791.PubMedCrossRef Plotkin H, Gundberg C, Mitnick M, et al. Dissociation of bone formation from resorption during two-week treatment with human parathyroid hormone-related peptide-(1–36) in humans: potential as an anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 1998;83(8):2786–2791.PubMedCrossRef
28.
go back to reference Bisello A, Horwitz MJ, Stewart AF. Parathyroid hormone-related protein: an essential physiological regulator of adult bone mass. Endocrinology. 2004;145(8):3551–3553.PubMedCrossRef Bisello A, Horwitz MJ, Stewart AF. Parathyroid hormone-related protein: an essential physiological regulator of adult bone mass. Endocrinology. 2004;145(8):3551–3553.PubMedCrossRef
Metadata
Title
The Expression of PTHLH in Human Gastric Mucosa Enterochromaffin-Like Cells
Authors
Cuiping Liu
Jianting Chen
Yu Guo
Lisheng Yang
Chengyi Zhao
Lan Bai
Publication date
01-04-2011
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 4/2011
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-010-1375-2

Other articles of this Issue 4/2011

Digestive Diseases and Sciences 4/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.