Regulation of parathyroid vitamin D receptor expression by extracellular calcium.
Low extracellular calcium (Ca) stimulates parathyroid hormone (PTH) secretion and also increases the renal synthesis of calcitriol (CTR), which is known to decrease PTH production. This study began with the hypothesis that the parathyroid cell response to CTR may be modulated by extracellular Ca concentration through an effect on parathyroid cell vitamin D receptor (VDR). In the present study, rat parathyroid glands were incubated in low (0.6 mM) and high (1.5 mM) Ca concentration. The parathyroid VDRmRNA was higher in 1.5 than 0.6 mM Ca. Furthermore, this effect was not observed in incubated slices of kidney cortex and medulla, tissues which also possess both Ca and vitamin D receptors. Experiments were also performed to evaluate the effect of Ca on VDR expression in vivo. Male Wistar rats received intraperitoneal injections of CaCl(2) or a single intramuscular injection of EDTA to obtain 6 h of hypercalcemic (ionized Ca, 1.4 to 1.6 mM) or hypocalcemic (ionized Ca, 0.85 to 0.95 mM) clamp; a third group of rats was used as control. A small dose of CTR was administered to hypercalcemic rats to match the serum CTR levels of hypocalcemic rats. Parathyroid gland VDRmRNA and VDR protein were increased in hypercalcemic rats as compared with hypocalcemic rats. Increasing doses of CTR upregulated VDRmRNA and VDR only in hypercalcemic rats. Additional experiments showed that the decrease in VDR in hypocalcemic rats prevented the inhibitory effect of CTR on PTHmRNA. In conclusion, our study shows that extracellular Ca regulates VDR expression by parathyroid cells independently of CTR and that by this mechanism hypocalcemia may prevent the feedback of CTR on the parathyroids.
Garfia
Bartolomé
B
Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, 14004 Córdoba, Spain.
Cañadillas
Sagrario
S
Canalejo
Antonio
A
Luque
Fernando
F
Siendones
Emilio
E
Quesada
Manuel
M
Almadén
Yolanda
Y
Aguilera-Tejero
Escolástico
E
Rodríguez
Mariano
M
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D006996:Hypocalcemia / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*
D002120:Calcium Channel Agonists; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol; D002118:Calcium