Opposite effects of 1,25(OH)2D3 on synthesis and release of PTH compared with secretory protein I.
Aggregates of bovine parathyroid cells (organoids) were cultured with or without 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and examined for effects on the synthesis, cellular content, and release of parathyroid hormone (PTH) and secretory protein I. Organoids cultured with 120 pM 1,25(OH)2D3 at 1.35 mM calcium contained 27 +/- 2% (mean +/- SE) less and released 26 +/- 7% less PTH and contained 21 +/- 2% more and released 49 +/- 16% more secretory protein I than untreated organoids. After 15-min incubations with radioactive leucine, treated organoids incorporated 25 +/- 2% less radioactivity into precipitable cellular proteins than did untreated organoids, indicating that the overall synthetic rate of proteins was decreased by 1,25(OH)2D3 at 1.35 mM calcium. After separation of cellular proteins by gel electrophoresis, analysis of individual protein bands indicated that the mean treated-control ratio for proparathyroid hormone radioactivity was 0.88 +/- 0.06 (P less than 0.10) while that for secretory protein I was 1.56 +/- 0.17 (P less than 0.01), respectively. Experiments were performed at 1.2, 12, 120, and 1,200 pM 1,25(OH)2D3 and both 1.4 and 1.8 mM calcium. In both cases, increasing levels of 1,25(OH)2D3 progressively decreased PTH synthesis and release and progressively increased that of secretory protein I, significant effects being observed at 1.2 pM 1,25(OH)2D3. We conclude that at physiological calcium levels, 1.2-1,200 pM 1,25(OH)2D3 suppresses the synthesis and secretion of PTH, increases that of secretory protein I, and at similar concentrations decreases the overall protein synthetic rate compared with untreated controls.
Ridgeway
R D
RD
Veterans Administration Medical Center, Kansas City, Missouri 64128.
MacGregor
R R
RR
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D053379:Chromogranin A; D002864:Chromogranins; D004305:Dose-Response Relationship, Drug; D009940:Organoids / Q000378:metabolism; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D053379:Chromogranin A; D002864:Chromogranins; D010281:Parathyroid Hormone; D002117:Calcitriol; D002118:Calcium