Type I membrane Klotho expression is decreased and inversely correlated to serum calcium in primary hyperparathyroidism
2008 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, no 10, 4152-4157 p.Article in journal (Refereed) Published
Context: The type I membrane protein Klotho was recently shownto mediate PTH secretion in parathyroid cells in response tolow extracellular calcium. In contrast, Klotho inhibits PTHsecretion indirectly through the action of fibroblast growthfactor-23. Abnormal Klotho expression in parathyroid disordersremains to be elucidated.
Objective: The aim of the study was to determine: 1) Klothoexpression in parathyroid adenomas from patients with primaryhyperparathyroidism (pHPT) compared to normal tissue; and 2)its relation to the serum calcium and PTH levels.
Design: Surgically removed parathyroid glands (n = 40) and fournormal parathyroid tissue specimens were analyzed for KlothomRNA and protein levels by quantitative real-time PCR and immunohistochemistry.In vitro effects of calcium on Klotho mRNA expression were studiedin bovine parathyroid cells.
Results: Klotho mRNA levels were significantly decreased (n= 23) or undetectable (n = 17) in parathyroid adenomas comparedto normal tissues (P < 0.001). Reduced Klotho protein expressionwas confirmed by immunohistochemistry. Klotho mRNA levels wereinversely correlated to serum calcium (r = –0.97; P <0.0001), and calcium dose-dependently decreased Klotho mRNAexpression in normal parathyroid cells in vitro (P < 0.01).Serum calcium was the only significant marker of Klotho expressionin multivariate analysis with calcium, phosphate, PTH, and adenomaweight as independent variables.
Conclusions: Parathyroid Klotho expression is decreased or undetectablein pHPT. We provide evidence that 1) serum calcium is stronglyassociated with parathyroid Klotho expression in pHPT; and 2)abnormal PTH secretion in hypercalcemic pHPT subjects is mediatedby Klotho-independent mechanisms.
Place, publisher, year, edition, pages
2008. Vol. 93, no 10, 4152-4157 p.
Klotho, Fibroblast growth factor-23, FGF23, FGF-23, pHPT, adenoma, primary hyperparathyroidism, calcium
Endocrinology and Diabetes
Research subject Medicine
IdentifiersURN: urn:nbn:se:uu:diva-107367DOI: 10.1210/jc.2008-0564ISI: 000259903700071OAI: oai:DiVA.org:uu-107367DiVA: diva2:228954
Björklund and Krajisnik contributed equally to this work.2009-08-122009-08-082015-06-16Bibliographically approved