Effects of 1,25-dihydroxyvitamin D3 and cortisol on bovine and human parathyroid cells

Abstract

ABSTRACT Incubation of bovine parathyroid cells with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) decreased both preproparathyroid mRNA levels and parathyroid hormone (PTH) secretion. There was a fall to 56·6 ± 13·7% (mean ± s.e.m.) and 65·1 ± 9·3% in mRNA levels and PTH secretion respectively at 1 nmol 1,25-(OH)2D3/l, and 41·1 ± 13·6% and 42·0 ± 12·1% at 10 nmol 1,25-(OH)2D3/l after 24 h. After 48 h in 0·1 nmol 1,25-(OH)2D3/l, mRNA levels had fallen to 35·3 ± 12·6% and PTH secretion to 32·1 ± 5·0%. In human adenomatous cells, however, incubation with 1,25-(OH)2D3 (10 nmol/l) had no effect on either mRNA levels or PTH secretion even after 48 h. This lack of sensitivity of adenomatous cells to 1,25-(OH)2D3 was not due to an absence of receptors (3847 ± 39 receptors/ng cytosolic protein in adenomatous cells compared with 4068 ± 371 in bovine cells) or receptors being of low affinity. Cortisol (1 μmol/l) caused a reduction in the number of receptors for 1,25-(OH)2D3 in bovine parathyroid cells of approximately 20% within 24 h of incubation, but no change in affinity. This decrease was accompanied by abolition of the response to 1,25-(OH)2D3 and was reversible, in that withdrawal of cortisol for the final 24 h of incubation was sufficient for the response to return, the number of receptors having returned to control values. These results suggest that only a small percentage of receptors for 1,25-(OH)2D3 in bovine parathyroid cells may be functional at any one time. Furthermore, the insensitivity of human adenomatous cells to 1,25-(OH)2D3 does not seem to be due to a lack of receptors but may be due to a defect in the interaction between the receptor protein and the PTH gene. Journal of Endocrinology (1989) 123, 137–142