title: New form of pseudohypoparathyroidism with abnormal catalytic adenylate cyclase.
abstract: Patients with pseudohypoparathyroidism type Ia have resistance to multiple hormones because of deficient activity of the stimulatory guanine nucleotide-binding protein (Gs) that couples membrane receptors to activation of adenylate cyclase. However, in a subset of patients with pseudohypoparathyroidism who have resistance to multiple hormones yet possess normal erythrocyte membrane Gs activity, the biochemical abnormality responsible for hormone resistance has remained undefined. Cultured skin fibroblasts were derived from a patient with this atypical form of pseudohypoparathyroidism. In the patient's fibroblast membranes, adenylate cyclase stimulation mediated by Gs after fluoride ion treatment produced only 52% of normal activity, yet fibroblast membrane Gs activity measured by cyc- complementation was normal. Activation of the catalytic unit of adenylate cyclase with manganese produced 49% of normal activity; manganese plus forskolin produced 54% of normal adenylate cyclase activity. beta-Adrenergic receptor coupling to Gs and phosphodiesterase activity were normal. A defect in the catalytic unit of adenylate cyclase can account for these results and may be a mechanism for clinical resistance to multiple hormones that act through adenylate cyclase.
authors.affiliation: Division of Endocrinology and Metabolism, Medical College of Virginia, Richmond 23298.
authors.forename: D
authors.initials: D
authors.lastname: Barrett
authors.forename: N A
authors.initials: NA
authors.lastname: Breslau
authors.forename: M B
authors.initials: MB
authors.lastname: Wax
authors.forename: P B
authors.initials: PB
authors.lastname: Molinoff
authors.forename: R W
authors.initials: RW
authors.lastname: Downs
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005973:Glutamine / Q000031:analogs & derivatives / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D011547:Pseudohypoparathyroidism / Q000201:enzymology*; D012016:Reference Values; D012867:Skin / Q000201:enzymology*
chemical_list: C032007:aceglutamide; D005973:Glutamine; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D007545:Isoproterenol