Stimulation of 1,25-dihydroxyvitamin D production by parathyroid hormone and dibutyryl 3',5'-cyclic AMP in normal subjects, hypoparathyroidism and pseudohypoparathyroidism.
Parathyroid extract (PTE) or synthetic 1-34 human parathyroid hormone (1-34 hPTH) was injected intravenously as a bolus in 4 normal subjects, 4 patients with PTH deficient hypoparathyroidism (HP) and 3 patients with pseudohypoparathyroidism (PHP). In normal subjects and HP, plasma 1,25(OH)2D was markedly increased at 6 hr and reached the peak at 12 or 14 hr after administration of 200 units of PTE or 20 to 30 micrograms of 1-34hPTH. On the other hand, 500 units of PTE or 20 micrograms of 1-34hPTH failed to increase plasma 1,25(OH)2D in PHP. However, 2.5 mg/kg of dibutyryl cAMP remarkably increased plasma 1,25(OH)2D in a patient with PHP. Maximal increments of plasma 1,25(OH)2D in 3 patients with HP(21.7 +/- 5.6 pg/ml, mean +/- S.D.) were nearly as high as in normal subjects (20.6 +/- 7.0 pg/ml), whereas those in 3 patients with PHP (2.3 +/- 2.3 pg/ml) were distinctly lower than in normal subjects or HP. It is suggested that 1,25(OH)2D production by PTH is intact in HP, but is impaired in PHP mainly due to a defect in the activation of adenylate cyclase system.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D003994:Bucladesine / Q000494:pharmacology*; D002117:Calcitriol / Q000096:biosynthesis*; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011547:Pseudohypoparathyroidism / Q000378:metabolism*; D013268:Stimulation, Chemical; D014807:Vitamin D / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D014807:Vitamin D; D003994:Bucladesine; D000262:Adenylyl Cyclases; D002117:Calcitriol