Abstract | CONTEXT: OBJECTIVE: DESIGN: Surgically removed parathyroid glands (n = 40) and four normal parathyroid tissue specimens were analyzed for Klotho mRNA and protein levels by quantitative real-time PCR and immunohistochemistry. In vitro effects of calcium on Klotho mRNA expression were studied in bovine parathyroid cells. RESULTS: Klotho mRNA levels were significantly decreased (n = 23) or undetectable (n = 17) in parathyroid adenomas compared to normal tissues (P < 0.001). Reduced Klotho protein expression was confirmed by immunohistochemistry. Klotho mRNA levels were inversely correlated to serum calcium (r = -0.97; P < 0.0001), and calcium dose-dependently decreased Klotho mRNA expression in normal parathyroid cells in vitro (P < 0.01). Serum calcium was the only significant marker of Klotho expression in multivariate analysis with calcium, phosphate, PTH, and adenoma weight as independent variables. CONCLUSIONS: Parathyroid Klotho expression is decreased or undetectable in pHPT. We provide evidence that 1) serum calcium is strongly associated with parathyroid Klotho expression in pHPT; and 2) abnormal PTH secretion in hypercalcemic pHPT subjects is mediated by Klotho-independent mechanisms.
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Authors | Peyman Björklund, Tijana Krajisnik, Göran Akerström, Gunnar Westin, Tobias E Larsson |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 93
Issue 10
Pg. 4152-7
(Oct 2008)
ISSN: 0021-972X [Print] United States |
PMID | 18682507
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Proteins
- Parathyroid Hormone
- Glucuronidase
- Klotho Proteins
- Calcium
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Topics |
- Adenoma
(blood, genetics, metabolism, pathology)
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Animals
- Calcium
(blood)
- Cattle
- Cells, Cultured
- Down-Regulation
- Female
- Gene Expression Regulation, Neoplastic
- Glucuronidase
(genetics, metabolism)
- Humans
- Hyperparathyroidism, Primary
(blood, genetics, metabolism)
- Klotho Proteins
- Male
- Membrane Proteins
(genetics, metabolism)
- Middle Aged
- Parathyroid Hormone
(blood)
- Parathyroid Neoplasms
(blood, genetics, metabolism, pathology)
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