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Calcium-Sensing Receptor Expression and Parathyroid Hormone Secretion in Hyperplastic Parathyroid Glands from Humans

Sagrario Cañadillas^*, Antonio Canalejo, Rafael Santamaría, Maria E. Rodríguez^*, Jose C. Estepa, Alejandro Martín-Malo, Juan Bravo^||, Blanca Ramos^¶, Escolastico Aguilera-Tejero, Mariano Rodríguez^* and Yolanda Almadén^*

^* Research Unit, Nephrology Service, Hospital Universitario Reina Sofia, Department of Animal Medicine and Surgery, Veterinary School, University of Cordoba, Cordoba, Spain; Department of Environmental Biology and Public Health, University of Huelva, Huelva, Spain; ^|| Nephrology Service, Hospital Virgen de las Nieves, Granada, Spain; and ^¶ Nephrology Service, Hospital Carlos Haya, Malaga, Spain

Address correspondence to: Dr. Mariano Rodriguez, Unidad de Investigación, Hospital Universitario Reina Sofia, Avd Menendez Pidal s/n, Cordoba 14004, Spain. Phone: 34-957-011040; Fax: 34-957-010452; E-mail: juanm.rodriguez.sspa{at}juntadeandalucia.es

Received for publication August 11, 2004. Accepted for publication March 22, 2005.

In uremic patients, severe parathyroid hyperplasia is associated with reduced parathyroid calcium-sensing receptor (CaR) expression. Thus, in these patients, a high serum Ca concentration may be required to inhibit parathyroid hormone (PTH) secretion. This study compares the magnitude of reduction in CaR expression and the degree of the abnormality in Ca-regulated PTH release in vitro. A total of 50 glands from 23 hemodialysis patients with refractory hyperparathyroidism were studied. Tissue slices were incubated in vitro to evaluate (1) the PTH secretory output in a normal Ca concentration (1.25 mM) and (2) the PTH secretory response to high (1.5 mM) and low (0.6 mM) Ca concentration. Tissue aliquots were processed for determination of CaRmRNA expression. The results showed that, corrected for DNA, parathyroid tissue with lowest CaR expression secreted more PTH than that with relatively high CaR expression (146 ± 23 versus 60 ± 2 pg/µg DNA; P < 0.01). Furthermore, glands with low CaR expression demonstrated a blunted PTH secretory response to both the inhibitory effect of high Ca and the stimulatory effect of low Ca. The study also showed that the larger the gland, the lower the CaRmRNA expression. Thus, large parathyroid glands produce a large amount of PTH not only as a result of the increased gland size but also because the parathyroid tissue secretory output is increased. These abnormalities in PTH regulation are related to low CaR expression.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673