Effects of 1,25-dihydroxyvitamin D3 and cortisol on bovine and human parathyroid cells.
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 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Karmali
R
R
Department of Medicine, Middlesex Hospital, London.
Farrow
S
S
Hewison
M
M
Barker
S
S
O'Riordan
J L
JL
D000236:Adenoma / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D013997:Time Factors
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol; D006854:Hydrocortisone