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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 Dec;62(6):1222–1227. doi: 10.1172/JCI109242

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

M K Drezner, W M Burch Jr
PMCID: PMC371887  PMID: 219026

Abstract

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 we 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 Km 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 our 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.

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Selected References

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