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.
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