Altered activity of the nucleotide regulatory site in the parathyroid hormone sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism

Journal Article

A series of clinical studies suggest that the primary defect underlying pseudohypoparathyroidism is an abnormality of the parathyroid hormone-receptor-adenylate cyclase complex of the renal cortical cell plasma membrane. In the present study the authors compared parathyroid hormone-stimulated adenylate cyclase activity in membrane preparations from the renal cortex of three controls and a patient with pseudohypoparathyroidism. In the pseudohypoparathyroid preparation the K(m) for ATP was significantly greater and parathyroid hormone elicited markedly diminished adenylate cyclase activity at a subsaturating concentration of ATP. In contrast, the dose-response effect of enzyme activity to parathyroid hormone was the same in the control preparations, and that of the pseudohypoparathyroidism kidney, at a saturating concentration of ATP. The apparent alteration in enzyme kinetics, however, was normalized upon addition of guanosine 5'-triphosphate to the reaction mixtures. These results indicate that the defect in the parathyroid hormone-receptor-adenylate cyclase complex of the renal cell membranes, in authors' patient with pseudohypoparathyroidism, is an abnormal nucleotide receptor site of decreased activity. Such a defect may result in partial uncoupling of the parathyroid hormone receptor and adenylate cyclase, rendering the organ refractory to hormonal stimulation.

Full Text

Duke Authors

Cited Authors

  • Drezner, MK; Jr, WMB

Published Date

  • 1978

Published In

  • Journal of Clinical Investigation

Volume / Issue

  • 62 / 6

Start / End Page

  • 1222 - 1227

PubMed ID

  • 219026

Digital Object Identifier (DOI)

  • 10.1172/JCI109242