Regulation of 1,25 (OH)2D synthesis in hypoparathyroidism and pseudohypoparathyroidism

We examined the regulation of 1,25-dihydroxyvitamin D [1,25(OH)2D] synthesis in patients with hypoparathyroidism (n = 5) and pseudohypoparathyroidism (n = 5) by administration of parathyroid extract (PTE) and N6,O2-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and by phosphorus deprivation with antacids. In response to PTE, patients with hypoparathyroidism increased serum 1,25(OH)2D from 17 +/- 5 to 30 +/- 5 (SD) pg/ml (P less than 0.01). An approximate doubling of the 1,25(OH)2D concentration also occurred following dbcAMP infusion or phosphorus deprivation (serum phosphorus 4.4 +/- 0.5 to 2.6 +/- 1.1, P less than 0.01). Serum phosphorus and 1,25(OH)2D concentrations were inversely correlated (r = -0.73, P less than 0.001). Patients with pseudohypoparathyroidism had negligible responses to PTE with respect to urinary adenosine 3', 5'-cyclic monophosphate excretion, serum phosphorus concentration, or 1,25(OH)2D synthesis. They did show a rise in serum 1,25(OH)2D from 17 +/- 4 to 44 +/- 5 pg/ml (P less than 0.001) in response to dbcAMP infusion. During phosphorus deprivation, serum phosphorus decreased from 4.1 +/- 0.8 to 3.2 +/- 1.2 mg/dl (P less than 0.05), but there was no change in serum 1,25(OH)2D concentration or any correlation between serum phosphorus and 1,25(OH)2D levels. Although reduction in mean serum phosphorus levels was generally not as great in patients with pseudohypoparathyroidism, one such patient attained serum phosphorus of 1.2 mg/dl and still did not increase serum 1,25(OH)2D concentration. In addition to an abnormal parathyroid hormone receptor-adenylate cyclase complex, patients with pseudohypoparathyroidism appear to have an abnormal renal 1 alpha-hydroxylase, which does not respond appropriately to phosphate deprivation.

Effects of parathyroid hormone on puppies during development of Ca and vitamin D deficiency

The acute effects of parathyroid extract (PTE) were studied repeatedly in young dogs (prelabeled with 45Ca and [3H]tetracycline) during the development of calcium (Ca) and vitamin D deficiency. Blood Ca and radioactivity changes were monitored sequentially after subcutaneous PTE, injected seven times over 63 days. In control dogs, all sequential responses to acute PTE challenges were constant in both magnitude of increase and time at which maximum response occurred over the entire experiment. Under chronic Ca and D deficiency, plasma 25-hydroxyvitamin D in experimental dogs decreased continuously to very low levels at 63 days, whereas 1,25-dihydroxyvitamin D initially increased to a maximum at 32 days and thereafter decreased. In response to an acute challenge of PTE, dogs on the deficient diet for 3 and 10 days showed a greater response of blood Ca and 45Ca than the controls but subsequently showed a smaller response than controls after 49 and 63 days on the deficient diet. Compared with control dogs, the time of maximal response of blood Ca and 45Ca to PTE occurred much earlier in dogs that were on the deficient diet for 35-63 days. The blood [3H]tetracycline response (index of bone resorption) to exogenous PTE in the deficient dogs, however, was constant and similar to that of the control dogs during the entire period. The data suggest that the bone resorption response to PTE was normal in Ca- and D-deficient puppies with hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Handling of phosphate by a parotid gland (ovine)

The handling of phosphate by the sheep's parotid gland was investigated by examining the effects on the composition of saliva of phosphate depletion, secretomotor nerve stimulation, enrichment of phosphate in the blood supply, and parotid arterial infusion of parathyroid hormone (PTH) and calcitonin. Experiments were performed in anesthetized sheep after vascular isolation of the parotid gland. In phosphate depletion arterial plasma phosphate fell from 1.50 +/- 0.12 to 0.73 +/- 0.08 mM. In phosphate repletion salivary phosphate ion was concentrated 8- and 16-fold compared with parotid arterial and venous plasma, respectively. In depletion salivary phosphate concentration was unchanged at slow salivary flow rate but was significantly lower at high flow rate. Enrichment of phosphate in the arterial blood increased salivary phosphate concentration in both situations. Synthetic bPTH (1-34), highly purified bPTH (1-84), and bovine parathyroid extract were equipotent in increasing salivary phosphate concentration in phosphate repletion and had no effect in phosphate depletion. They also increased parotid blood flow. The rise in phosphate with PTH was conditional on the rise in blood flow, but the same rise in blood flow alone did not reproduce the effect of PTH on salivary phosphate. PTH increased work done and oxygen consumption by the gland but arterial phosphate enrichment did not. Increases in salivary phosphate were associated with decreases in salivary bicarbonate, and the sum [HCO-3] + [Cl-] + (HPO2-4] remained almost constant. Micropuncture studies have shown that ovine parotid ducts do not normally reabsorb phosphate and therefore PTH probably increases phosphate secretion in the endpieces.