Immunohistochemical identification of the PTHR1 parathyroid hormone
receptor in normal and neoplastic human tissues
A. Lupp, C. Klenk, C. Rocken, M. Evert, C. Mawrin, and S. Schulz. Eur J Endocrinol, 162 (5):
979-86(May 2010)Lupp, Amelie Klenk, Christoph Rocken, Christoph Evert, Matthias Mawrin,
Christian Schulz, Stefan England European journal of endocrinology
/ European Federation of Endocrine Societies Eur J Endocrinol. 2010
May;162(5):979-86. Epub 2010 Feb 15..
Abstract
BACKGROUND: Parathyroid hormone (PTH) is a crucial regulator of calcium
homoeostasis in humans. Although it is well known that PTH acts primarily
on kidney and bone, the precise cellular and subcellular sites of
PTH action have not been visualised in human tissues. METHOD: We
developed and characterised a novel anti-peptide antibody to the
carboxy-terminal region of the human PTH receptor type 1 (PTHR1).
Specificity of the antiserum was demonstrated by i) detection of
a broad band migrating at M(r) 85,000-95,000 in western blots of
membranes from human kidney and PTHR1-transfected cells; ii) cell
surface staining of PTHR1-transfected cells; iii) translocation of
PTHR1 receptor immunostaining after agonist exposure; and iv) abolition
of tissue immunostaining by preadsorption of the antibody with its
immunising peptide. The distribution of PTHR1 receptors was investigated
in 320 human tumours and their tissues of origin. RESULTS: In the
kidney, PTHR1 receptors were predominantly detected at the basolateral
plasma membrane of epithelial cells in the proximal and distal tubules
but not in the thin limbs of Henle, collecting ducts or glomeruli.
In bone, PTHR1 receptors were detected as discrete plasma membrane
staining of osteocytes and osteoblasts, whereas osteoclasts remained
unstained. In addition, PTHR1 was found in the gut and in a number
of neoplastic tissues including colorectal carcinoma, prostate cancer,
renal cell carcinoma and osteosarcoma. CONCLUSION: This is the first
localisation of PTHR1 receptors in human tissues at the cellular
level. The overexpression of PTHR1 receptors may provide a molecular
basis for efficient targeting of human tumours with radiolabelled
PTH analogues.
Lupp, Amelie Klenk, Christoph Rocken, Christoph Evert, Matthias Mawrin,
Christian Schulz, Stefan England European journal of endocrinology
/ European Federation of Endocrine Societies Eur J Endocrinol. 2010
May;162(5):979-86. Epub 2010 Feb 15.
%0 Journal Article
%1 Lupp2010
%A Lupp, A.
%A Klenk, C.
%A Rocken, C.
%A Evert, M.
%A Mawrin, C.
%A Schulz, S.
%D 2010
%J Eur J Endocrinol
%K 1/*analysis/immunology Animals Bone Bones/chemistry CHO Carcinoma, Cell/chemistry Colorectal Cricetinae Cricetulus Hormone, Humans Immunohistochemistry Intestines/chemistry Kidney/chemistry Male Neoplasms/chemistry Osteosarcoma/chemistry Parathyroid Prostatic Renal Type and Receptor Cell
%N 5
%P 979-86
%T Immunohistochemical identification of the PTHR1 parathyroid hormone
receptor in normal and neoplastic human tissues
%U http://www.ncbi.nlm.nih.gov/pubmed/20156969
%V 162
%X BACKGROUND: Parathyroid hormone (PTH) is a crucial regulator of calcium
homoeostasis in humans. Although it is well known that PTH acts primarily
on kidney and bone, the precise cellular and subcellular sites of
PTH action have not been visualised in human tissues. METHOD: We
developed and characterised a novel anti-peptide antibody to the
carboxy-terminal region of the human PTH receptor type 1 (PTHR1).
Specificity of the antiserum was demonstrated by i) detection of
a broad band migrating at M(r) 85,000-95,000 in western blots of
membranes from human kidney and PTHR1-transfected cells; ii) cell
surface staining of PTHR1-transfected cells; iii) translocation of
PTHR1 receptor immunostaining after agonist exposure; and iv) abolition
of tissue immunostaining by preadsorption of the antibody with its
immunising peptide. The distribution of PTHR1 receptors was investigated
in 320 human tumours and their tissues of origin. RESULTS: In the
kidney, PTHR1 receptors were predominantly detected at the basolateral
plasma membrane of epithelial cells in the proximal and distal tubules
but not in the thin limbs of Henle, collecting ducts or glomeruli.
In bone, PTHR1 receptors were detected as discrete plasma membrane
staining of osteocytes and osteoblasts, whereas osteoclasts remained
unstained. In addition, PTHR1 was found in the gut and in a number
of neoplastic tissues including colorectal carcinoma, prostate cancer,
renal cell carcinoma and osteosarcoma. CONCLUSION: This is the first
localisation of PTHR1 receptors in human tissues at the cellular
level. The overexpression of PTHR1 receptors may provide a molecular
basis for efficient targeting of human tumours with radiolabelled
PTH analogues.
@article{Lupp2010,
abstract = {BACKGROUND: Parathyroid hormone (PTH) is a crucial regulator of calcium
homoeostasis in humans. Although it is well known that PTH acts primarily
on kidney and bone, the precise cellular and subcellular sites of
PTH action have not been visualised in human tissues. METHOD: We
developed and characterised a novel anti-peptide antibody to the
carboxy-terminal region of the human PTH receptor type 1 (PTHR1).
Specificity of the antiserum was demonstrated by i) detection of
a broad band migrating at M(r) 85,000-95,000 in western blots of
membranes from human kidney and PTHR1-transfected cells; ii) cell
surface staining of PTHR1-transfected cells; iii) translocation of
PTHR1 receptor immunostaining after agonist exposure; and iv) abolition
of tissue immunostaining by preadsorption of the antibody with its
immunising peptide. The distribution of PTHR1 receptors was investigated
in 320 human tumours and their tissues of origin. RESULTS: In the
kidney, PTHR1 receptors were predominantly detected at the basolateral
plasma membrane of epithelial cells in the proximal and distal tubules
but not in the thin limbs of Henle, collecting ducts or glomeruli.
In bone, PTHR1 receptors were detected as discrete plasma membrane
staining of osteocytes and osteoblasts, whereas osteoclasts remained
unstained. In addition, PTHR1 was found in the gut and in a number
of neoplastic tissues including colorectal carcinoma, prostate cancer,
renal cell carcinoma and osteosarcoma. CONCLUSION: This is the first
localisation of PTHR1 receptors in human tissues at the cellular
level. The overexpression of PTHR1 receptors may provide a molecular
basis for efficient targeting of human tumours with radiolabelled
PTH analogues.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Lupp, A. and Klenk, C. and Rocken, C. and Evert, M. and Mawrin, C. and Schulz, S.},
biburl = {https://www.bibsonomy.org/bibtex/21be0e1c352e03fef842f21cab288ae44/pharmawuerz},
endnotereftype = {Journal Article},
groups = {private},
interhash = {63a8667ef7e059f1dc75dd62d924d1ea},
intrahash = {1be0e1c352e03fef842f21cab288ae44},
issn = {1479-683X (Electronic) 0804-4643 (Linking)},
journal = {Eur J Endocrinol},
keywords = {1/*analysis/immunology Animals Bone Bones/chemistry CHO Carcinoma, Cell/chemistry Colorectal Cricetinae Cricetulus Hormone, Humans Immunohistochemistry Intestines/chemistry Kidney/chemistry Male Neoplasms/chemistry Osteosarcoma/chemistry Parathyroid Prostatic Renal Type and Receptor Cell},
month = May,
note = {Lupp, Amelie Klenk, Christoph Rocken, Christoph Evert, Matthias Mawrin,
Christian Schulz, Stefan England European journal of endocrinology
/ European Federation of Endocrine Societies Eur J Endocrinol. 2010
May;162(5):979-86. Epub 2010 Feb 15.},
number = 5,
pages = {979-86},
shorttitle = {Immunohistochemical identification of the PTHR1 parathyroid hormone
receptor in normal and neoplastic human tissues},
timestamp = {2010-12-14T18:20:40.000+0100},
title = {Immunohistochemical identification of the PTHR1 parathyroid hormone
receptor in normal and neoplastic human tissues},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20156969},
volume = 162,
year = 2010
}