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Activity of the Stimulatory Guanine Nucleotide-Binding Protein Is Reduced in Erythrocytes from Patients with Pseudohypoparathyroidism and Pseudopseudohypoparathyroidism: Biochemical, Endocrine, and Genetic Analysis of Albright's Hereditary Osteodystrophy in Six Kindreds^*

Department of Medicine, The Johns Hopkins University School of Medicine Baltimore, Maryland 21205
Department of Pediatrics, University of Washington Seattle, Washington 98105
Department of Medicine, Medical College of Virginia Richmond, Virginia 23298
Metabolic Diseases Branch, National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, National Institutes of Health Bethesda, Maryland 20205

Address all correspondence and requests for reprints to: Michael A.Levine, M.D., Department of Medicine-Endocrinology, Johns Hopkins University, Traylor Building, Room 721, 720 Rutland Avenue, Baltimore,Maryland 21205.

Multiple hormone resistance in many patientswith pseudohypoparathyroidism (PHP) type la and Albright'shereditary osteodystrophy (AHO) is associated with deficient activity of the stimulatory guanine nucleotide-binding protein (Gs) of adenylate cyclase. To study further the relationship od deficient Gs activity to hormone resistance, we evaluated endocrine function and measured Gs activity of erythrocyte membranes from AHO patients with clinical hormone resistance (PHP type la) and from family members with AHO alone (pseudopseudohypoparathyroidism). The resultsof erythrocyte membrane Gs determinations were compared to those of unaffected relatives and normal subjects. Patients with pseudopseu dohypoparathyroidism(pseudoPHP) had reductions in erythrocytemembrane Gs activity comparable to those in patients with PHP type la [43.4 ± 11.9% (±SD) for PHP type la vs. 47.8± 9.5% for pseudoPHP]. However, in contradistinction to patients with PHP type la,individuals with pseudoPHP did not have obvious endocrine dysfunction. Although deficient Gs activity appears to play an important role in the pathogenesis of these disorders,it is possible that Gs deficiency must be combined with other factors that limit cAMP production to cause clinically overt endocrine disease.

^* This work was supported in part by a Clinical Associate Physician Award (to M.A.L.) from the General Research Centers Branch, Division of Research Resources, NIH, and by Basil O'Connor Starter Research Grant 5-464 (to M.A.L.) from the March of Dimes-Birth Defects Foundation.

Received August 8, 1985.

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