Response of parathyroid glands to calcitriol in culture: Is this response mediated by the genetic polymorphisms in vitamin D receptor?
BACKGROUND
Recently, we have developed a model of parathyroid tissue culture that allows the study of the response of the parathyroid glands to long-term effectors, such as calcitriol, and that is also useful to study the likely effect of the genetic polymorphisms in the functionality of the glands. The aim of this study was to evaluate the response to calcitriol of cultured parathyroid tissue from patients with secondary hyperparathyroidism (HPT) and the possible effect of vitamin D receptor (VDR) gene polymorphisms on this response.


METHODS
Parathyroid glands (N = 37) from 34 parathyroidectomized patients (17 men, 17 women) were used. Several gland fragments were cultured for 60 hours in the presence of calcitriol 10(-9) mol/L or 10(-8) mol/L. DNA from each fragment was extracted to normalize the hormone secretion levels and to genotype the restriction sites ApaI, BsmI, TaqI, and FokI in the VDR gene.


RESULTS
The percentages of secretion observed in the response to calcitriol were: 69%+/- 28% (range, 3-100) and 46%+/- 19% (range, 8-78) for calcitriol 10(-9) mol/L and 10(-8) mol/L, respectively (P = 0.004). None of the polymorphisms showed statistical differences in response to calcitriol with any of the concentrations used.


CONCLUSIONS
Parathyroid glands cultured in vitro from patients with secondary HPT are able to respond to calcitriol decreasing PTH synthesis. These results, however, do not support the current hypothesis that VDR polymorphisms are involved in the modulation of the parathyroid gland response.
Alvarez-Hernández
Daniel
D
Bone and Mineral Research Unit, Hospital Central de Asturias, Instituto Reina Sofía de Investigación, Oviedo, Spain.
Naves
Manuel
M
Santamaría
Iñigo
I
Menárguez
Javier
J
Torregrosa
Vicente
V
Cannata
Jorge
J
D000328:Adult; D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D010280:Parathyroid Glands / Q000187:drug effects*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018167:Receptors, Calcitriol; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific; D002117:Calcitriol