Regulation of preproparathyroid hormone messenger RNA and hormone synthesis in human parathyroid adenomata.
Preproparathyroid hormone (preproPTH) mRNA and PTH secretion were measured in human parathyroid adenomata (n = 8) cultured in 1.0 or 3.0 mmol calcium/l and compared with changes in bovine parathyroid glands (n = 3) as a control. Incubation of bovine glands in 3.0 mmol calcium/l for 24 h resulted in a fall in mRNA levels to 47.3 +/- 21.7% (mean +/- S.D.) compared with cells incubated in 1.0 mmol calcium/l, with a concomitant decrease in secretion to 62.6 +/- 10.8%. These values fell further to 30.1 +/- 15.5% and 42.1 +/- 18.7% respectively after 48-h incubation. One human adenoma responded to high levels of calcium in a similar manner with mRNA levels falling to 44.6 +/- 11.9% and secretion to 30.3 +/- 17.3% within 24 h. However, in the majority of adenomata (seven out of eight), after 24-h incubation in 3.0 mmol calcium/l, mRNA levels fell to 54.1 +/- 14.6% but there was no change in secretion. In two of these adenomata which were cultured for 48 h, there was no suppression of secretion despite mRNA levels having fallen to approximately 60% of control. Incorporation of [35S]methionine into PTH secreted from human adenomatous cells was quantified by densitometry. There was no difference in the amount of radiolabelled PTH secreted from cells incubated in high levels of calcium compared with those in normal levels of calcium. In similar experiments, the effects of high calcium on the synthesis of PTH in bovine cells was assessed by determination of radiolabelled intracellular PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
Farrow
S M
SM
Department of Medicine, Middlesex Hospital, London.
Karmali
R
R
Gleed
J H
JH
Hendy
G N
GN
O'Riordan
J L
JL
D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D006801:Humans; D008970:Molecular Weight; D010281:Parathyroid Hormone / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors
D010281:Parathyroid Hormone; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; C019056:preproparathormone; D002118:Calcium