Fibroblast defect in pseudohypoparathyroidism, type I: reduced activity of receptor-cyclase coupling protein.
Erythrocytes of many patients with pseudohypoparathyroidism, type I (PHP-I), exhibit reduced activity of the N protein, a guanine nucleotide-binding regulatory component of hormone-sensitive adenylate cyclase. We compared N and adenylate cyclase activities and the accumulation of cAMP in fibroblasts propagated from skin biopsies of six normal subjects and seven PHP-I patients. N activities were reduced by approximately 40% in fibroblasts as well as erythrocytes of five PHP-I patients. N activities in fibroblasts from two PHP-I patients with normal erythrocyte N activities were within the normal range. These results are consistent with the hypothesis that N deficiency is generalized in tissues of most PHP-I patients and is the primary defect responsible for their resistance to metabolic effects of hormones that work by stimulating adenylate cyclase. Fibroblast N deficiency was not associated with decreases in hormone-stimulated adenylate cyclase or cAMP accumulation in fibroblasts, probably because these activities involve many potentially regulable cellular components in addition to the N protein.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000652:urine; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D019204:GTP-Binding Proteins; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone; D011458:Prostaglandins E / Q000494:pharmacology; D011547:Pseudohypoparathyroidism / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D006150:Guanine Nucleotides; D010281:Parathyroid Hormone; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases