The in vitro effect of calcitriol on parathyroid cell proliferation and apoptosis.
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 degrees) and primary (1 degree) 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 degrees 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 degrees 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 degree 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.
Canalejo
Antonio
A
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba.
Almadén
Yolanda
Y
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba.
Torregrosa
Vicente
V
Nephrology Service, Hospital Clinic, Barcelona.
Gomez-Villamandos
Jose C
JC
Department of Pathology, Veterinary Faculty, University of Córdoba, Córdoba.
Ramos
Blanca
B
Nephrology Service, Carlos Haya Hospital, Malaga, Spain.
Campistol
Jose M
JM
Nephrology Service, Hospital Clinic, Barcelona.
Felsenfeld
Arnold J
AJ
Department of Medicine, West Los Angeles VA Medical Center and UCLA, Los Angeles, California.
Rodríguez
Mariano
M
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba.
D000236:Adenoma / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D004285:Dogs; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D010280:Parathyroid Glands / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D010282:Parathyroid Neoplasms / Q000473:pathology; D012016:Reference Values
D002120:Calcium Channel Agonists; D002117:Calcitriol