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Published on: March 14, 2017
Expression of parathyroid hormone-related protein in abnormal human parathyroids
H M Docherty1, W A Ratcliffe, D A Heath
1Department of Medicine, University of Birmingham, Queen Elizabeth Hospital.
Abstract:
The expression of parathyroid hormone-related protein (PTHrP) in abnormal human parathyroids was investigated. Northern blot analysis of RNA extracted from human benign parathyroid adenomata (n = 4) revealed multiple PTHrP mRNA species ranging in size from 1.8 to 4 kb. The relative abundance of PTHrP mRNA expressed in two of the adenomata was similar to that of a tumour (DAF) associated with humoral hypercalcaemia of malignancy, whereas PTHrP mRNA was of low abundance in a third and was undetectable in the fourth. PTHrP-like immunoreactivity was detected in extracts of abnormal parathyroid tissue (benign adenoma (n = 7), hyperplasia (n = 5) and parathyroid carcinoma (n = 2] using a sensitive specific two-site immunoradiometric assay for human (h) PTHrP(1-86) and a radioimmunoassay for hPTHrP(1-34). Ratios of hPTHrP(1-86)- and hPTHrP(1-34)-like immunoreactivities relative to hPTH(1-84)-like immunoreactivity in the parathyroid tissue extracts were, on average, less than 1%. PTHrP bioactivity in the extracts could not be distinguished from that of PTH, by an osteosarcoma cell bioassay. We conclude that, despite reports of over-expression of PTHrP mRNA in parathyroid adenomata, the potential contribution of PTHrP to the total PTH-like activity of adenomata and other abnormal parathyroid tissue may be insignificant relative to PTH.
Insights
Parathyroid hormone-related protein (PTHrP) mRNA is found in abnormal parathyroid tissue, but its contribution to overall PTH-like activity is minimal compared to parathyroid hormone (PTH). This suggests PTHrP may not significantly impact hypercalcemia in these conditions.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Parathyroid hormone-related protein (PTHrP) is implicated in humoral hypercalcemia of malignancy.
- Its role in abnormal parathyroid conditions, such as adenomas and hyperplasia, requires further investigation.
Purpose of the Study:
- To investigate the expression and activity of PTHrP in human parathyroid adenomas, hyperplasia, and carcinoma.
- To determine the relative contribution of PTHrP to the total PTH-like activity in these abnormal tissues.
Main Methods:
- Northern blot analysis of PTHrP mRNA in parathyroid adenomas.
- Immunoradiometric and radioimmunoassays to detect PTHrP-like immunoreactivity in abnormal parathyroid tissues.
- Osteosarcoma cell bioassay to assess PTHrP bioactivity.
Main Results:
- PTHrP mRNA species were detected in benign parathyroid adenomas, with varying abundance.
- PTHrP-like immunoreactivity was found in abnormal parathyroid tissues, but at levels less than 1% relative to PTH.
- PTHrP bioactivity could not be distinguished from PTH bioactivity in tissue extracts.
Conclusions:
- Despite detectable PTHrP mRNA in parathyroid adenomas, its contribution to the total PTH-like activity is likely insignificant.
- PTHrP's role in causing hypercalcemia in abnormal parathyroid conditions may be minimal compared to PTH.
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