title: In vitro stimulation of 25-hydroxycholecalciferol 1 alpha-hydroxylation by parathyroid hormone in chick kidney slices: evidence for a role for adenosine 3',5'-monophosphate.
abstract: We studied the effect of parathyroid hormone (PTH) on the in vitro conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] by kidney slices from vitamin D-deficient chicks. Bovine PTH (bPTH) stimulated 1,25-(OH)2D3 production at low concentrations, with maximal stimulation (65%) at a concentration of 25 ng/ml bPTH in the absence of theophylline. Higher concentrations of bPTH resulted in less stimulation. The addition of 5 mM theophylline to the incubation buffer decreased basal 1,25-(OH)2D3 production but potentiated the stimulation of 1,25-(OH)2D3 production by PTH. Maximal stimulation (170%) was observed with 2 ng/ml bPTH in the presence of theophylline. Maximal stimulation of cAMP production by the kidney slices required 2- to 3-fold larger concentrations of bPTH. However, cAMP by itself stimulated 1,25-(OH)2D3 production, with maximal stimulation (70%) at 10(-7)-10(-5) M cAMP. We conclude that stimulation by PTH of 1,25-(OH)2D3 production can be potentiated by theophylline and mimicked by cAMP. However, such stimulation occurs at PTH concentrations lower than that required for optimal stimulation of adenylate cyclase activity.
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D000242:Cyclic AMP / Q000502:physiology*; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology
chemical_list: D010281:Parathyroid Hormone; D013806:Theophylline; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase