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The In Vitro Effect of Calcitriol on Parathyroid Cell Proliferation and Apoptosis

ANTONIO CANALEJO^*, YOLANDA ALMADÉN^*, VICENTE TORREGROSA, JOSE C. GOMEZ-VILLAMANDOS, BLANCA RAMOS^§, JOSE M. CAMPISTOL, ARNOLD J. FELSENFELD^|| and MARIANO RODRÍGUEZ^*

^* Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba
Nephrology Service, Hospital Clinic, Barcelona
Department of Pathology, Veterinary Faculty, University of Córdoba, Córdoba
^§ Nephrology Service, Carlos Haya Hospital, Malaga, Spain
^|| Department of Medicine, West Los Angeles VA Medical Center and UCLA, Los Angeles, California.

Correspondence to Dr. Mariano Rodriguez, Unidad de Investigación, Hospital Reina Sofia, Avda Menendez Pidal s/n, 14004 Cordoba, Spain. Phone: 34-957-217229; Fax: 34-957-202542; E-mail: mrodriguez{at}sofia.hrs.sas.cica.es

Abstract. Calcitriol treatment is used to reduce parathyroid hormone levels in azotemic patients with secondary hyperparathyroidism (HPT). Whether long-term calcitriol administration reduces parathyroid gland size in patients with severe secondary hyperparathyroidism is not clear. The aim of the study was to evaluate in vitro the effect of calcitriol on parathyroid cell proliferation and apoptosis in normal parathyroid glands and in adenomatous and hyperplastic human parathyroid glands. Freshly harvested parathyroid glands from normal dogs and hyperplastic and adenomatous glands from patients with secondary (2°) and primary (1°) HPT undergoing parathyroidectomy were studied. Flow cytometry was used to quantify the cell cycle and apoptosis of parathyroid cells. Apoptosis was also evaluated by DNA electrophoresis and light and electron microscopy. In normal dog parathyroid glands, culture with calcitriol (10^-10 to 10^-7 M) for 24 h produced a dose-dependent inhibitory effect on the progression of cells into the cell cycle and into apoptosis. When glands from patients with 2°HPT were cultured for 24 h, only high calcitriol concentrations (10^-7 M) inhibited the progression through the cell cycle and the induction of apoptosis. In parathyroid adenomas (1°HPT), even a high concentration of calcitriol (10^-7 M) had no significant effect on the cell cycle or apoptosis. The present study shows that in vitro, calcitriol inhibits in a dose-dependent manner in normal parathyroid glands both parathyroid cell proliferation and apoptosis. However, in secondary hyperplasia, only high concentrations of calcitriol inhibited cell proliferation and apoptosis. In 1°HPT, even high concentrations of calcitriol had no effect. Because calcitriol simultaneously inhibits both cell proliferation and apoptosis, a reduction in the parathyroid gland mass may not occur as a direct effect of calcitriol treatment.

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