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.
Multiple hormone resistance in many patients with pseudohypoparathyroidism (PHP) type Ia and Albright's hereditary osteodystrophy (AHO) is associated with deficient activity of the stimulatory guanine nucleotide-binding protein (Gs) of adenylate cyclase. To study further the relationship of 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 Ia) and from family members with AHO alone (pseudopseudohypoparathyroidism). The results of erythrocyte membrane Gs determinations were compared to those of unaffected relatives and normal subjects. Patients with pseudopseudohypoparathyroidism (pseudoPHP) had reductions in erythrocyte membrane Gs activity comparable to those in patients with PHP type Ia [43.4 +/- 11.9% (+/- SD) for PHP type Ia vs. 47.8 +/- 9.5% for pseudoPHP]. However, in contradistinction to patients with PHP type Ia, 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.
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D000242:Cyclic AMP / Q000652:urine; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000494:pharmacology; D010375:Pedigree; D010641:Phenotype; D011547:Pseudohypoparathyroidism / Q000097:blood* / Q000235:genetics; D011556:Pseudopseudohypoparathyroidism / Q000097:blood* / Q000235:genetics; D013963:Thyroid Hormones / Q000097:blood
D010281:Parathyroid Hormone; D013963:Thyroid Hormones; D000242:Cyclic AMP; D019204:GTP-Binding Proteins