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.
M K Drezner, W M Burch Jr
Title and authors | Publication | Year |
---|---|---|
Vitamins & Hormones
KJ Hare, FK Knop |
Vitamins & Hormones | 2010 |
Hypoparathyroidism
D Shoback |
New England Journal of Medicine | 2008 |
Principles of Bone Biology
CJ Rosen, T Niu |
Principles of Bone Biology | 2008 |
Multihormonal Resistance to Parathyroid Hormone, Thyroid Stimulating Hormone, and Other Hormonal and Neurosensory Stimuli in Patients with Pseudohypoparathyroidism
JL Wimeau, AS Balavoine, M Ladsous, FL Velayoudom-Cephise, V Vlaeminck-Guillem |
Journal of Pediatric Endocrinology and Metabolism | 2006 |
Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms
H Murer, N Hernando, I Forster, J Biber |
Physiological reviews | 2000 |
Hormone Resistance Syndromes
JL Jameson |
1999 | |
Advances in Protein Chemistry
CM Silva, J Isgaard, MO Thorner |
Advances in Protein Chemistry | 1998 |
Targeted Disruption of Gnas in Embryonic Stem Cells*
WF Schwindinger, KJ Reese, AM Lawler, JD Gearhart, MA Levine |
Endocrinology | 1997 |
Pseudohypoparathyreoidismus und Nebennierenrindeninsuffizienz: Ein Fall von Multipler Endokrinopathie bei peripherer Hormonresistenz
P Ridderskamp, R Schlaghecke |
Klinische Wochenschrift | 1990 |
Decreased bioactivity of the guanine nucleotide-binding protein that stimulates adenylate cyclase in hearts from cardiomyopathic Syrian hamsters
PD Kessler, AE Cates, CV Dop, AM Feldman |
Journal of Clinical Investigation | 1989 |
Altered response of adenylate cyclase to parathyroid hormone during compensatory renal growth
CL Milanes, N Pernalete, R Starosta, M Perez-Gonzalez, V Paz-Martinez, E Bellorin-Font |
Kidney International | 1989 |
Hypocalcemic and hypercalcemic disorders in children
G Kainer, JC Chan |
Current Problems in Pediatrics | 1989 |
Vitamin D
A Portale, Β Halloran, E Lonergan, R Morris |
Vitamin D | 1988 |
Oligosymptomatic hypocalcaemia in a patient with impaired parathyroid hormone activity
A Lenox-Smith, W Smith, GA Ferns, C Moniz |
Journal of the Royal Society of Medicine | 1988 |
Phosphate homeostasis
PJ Butterworth |
Molecular Aspects of Medicine | 1987 |
Clinical Disorders of Membrane Transport Processes
TE Andreoli, JF Hoffman, DD Fanestil, SG Schultz |
1987 | |
Hormone Resistance and Other Endocrine Paradoxes
MP Cohen, PP Foà |
1987 | |
Proceedings of the 1985 Laurentian Hormone Conference
RM Carey, S Sen |
Proceedings of the 1985 Laurentian Hormone Conference | 1986 |
The Receptors
RG Rosenfeld, RL Hintz |
The Receptors | 1986 |
Clinical Endocrinology
A Labhart |
Clinical Endocrinology | 1986 |
Isoproterenol-sensitive adenylate cyclase in glomeruli isolated from young and adult rat renal cortex
C Judes, JJ Helwig, C Bollack, P Mandel |
General Pharmacology: The Vascular System | 1985 |
Contemporary Endocrinology
SH Ingbar |
1985 | |
Homeostasis, Nephrotoxicity, and Renal Anomalies in the Newborn
J Strauss |
1985 | |
Impaired formation of beta-adrenergic receptor-nucleotide regulatory protein complexes in pseudohypoparathyroidism
JA Heinsimer, AO Davies, RW Downs, MA Levine, AM Spiegel, MK Drezner, AD Lean, KA Wreggett, MG Caron, RJ Lefkowitz |
Journal of Clinical Investigation | 1984 |
Phosphate and Mineral Metabolism
SG Massry, G Maschio, E Ritz |
1984 | |
Renal refractoriness to PTH in experimental Fanconi syndrome: Evidence for intact adenylate cyclase activation
H Wald, MM Popovtzer |
Pflügers Archiv - European Journal of Physiology | 1984 |
Deficient adenylate cyclase regulatory protein in renal membranes from a patient with pseudohypoparathyroidism
RW Downs, MA Levine, MK Drezner, WM Burch, AM Spiegel |
Journal of Clinical Investigation | 1983 |
PSEUDOHYPOPARATHYROIDISM: INHERITANCE AND EXPRESSION OF DEFICIENT RECEPTOR-CYCLASE COUPLING PROTEIN ACTIVITY
JA Fischer, HR Bourne, MA Dambacher, F Tschopp, R Meyer, JP Devogelaer, EA Werder, CN Deuxchaisnes |
Clinical Endocrinology | 1983 |
Introduction: The clinical significance of peptide hormone receptors
KJ Gatt, ML Dufau |
Clinics in Endocrinology and Metabolism | 1983 |
Dünndarm A
F Bazzoli, R Böhmer, WF Caspary, H Dombrowski, B Eckhardt, B Elsenhans, A Encke, A Ferguson, W Forth, H Fromm, A Gangl, S Gutschmidt, U Hopfer, GJ Kreijs, B Lembcke, KH zum Büschenfelde, G Mödder, G Nell, HF Otto, H Peerenboom, G Rehner, G Rettenmaier, EO Riecken, JW Robinson, K Rommel, H Ruppin, J Seifert, KH Soergel, S Strobel, L Vollrath, R Wanitschke, HJ Weis |
1983 | |
Teratogenesis and Reproductive Toxicology
EM Johnson, DM Kochhar |
1983 | |
Albright's hereditary osteodystrophy: A review
N Fitch, JM Opitz, J Herrmann |
American Journal of Medical Genetics | 1982 |
Disorders of Mineral Metabolism
RK Rude, FR Singer |
Disorders of Mineral Metabolism | 1982 |
Regulation of Phosphate and Mineral Metabolism
SG Massry, JM Letteri, E Ritz |
1982 | |
BASAL GANGLIA CALCIFICATION IN PSEUDOHYPOPARATHYROIDISM TYPE II
R Windeck, U Menken, G Benker, D Reinwein |
Clinical Endocrinology | 1981 |
Down syndrome fibroblasts are hyperresponsive to beta-adrenergic stimulation
JD McSwigan, DR Hanson, A Lubiniecki, LL Heston, JR Sheppard |
Proceedings of the National Academy of Sciences | 1981 |
Cell cycle changes in the adenylate cyclase of C6 glioma cells
RF Howard, JR Sheppard |
The Journal of Cell Biology | 1981 |
Contemporary Nephrology
S Klahr, SG Massry |
1981 | |
Adenylate cyclase responsiveness to hormones in various portions of the human nephron
D Chabardès, M Gagnan-Brunette, M Imbert-Teboul, O Gontcharevskaia, M Montégut, A Clique, F Morel |
Journal of Clinical Investigation | 1980 |
Cellular Action of Vasopressin in Medullary Tubules of Mice with Hereditary Nephrogenic Diabetes Insipidus
BA Jackson, RM Edwards, H Valtin, TP Dousa |
Journal of Clinical Investigation | 1980 |
Demonstration of a lack of change in serum 1 alpha,25-dihydroxyvitamin D in response to parathyroid extract in pseudohypoparathyroidism
PW Lambert, BW Hollis, NH Bell, S Epstein |
Journal of Clinical Investigation | 1980 |
Studies on the attainment of normocalcemia in patients with pseudohypoparathyroidism
NA Breslau, DD Notman, JM Canterbury, AM Moses |
The American Journal of Medicine | 1980 |
Defect of Receptor–Cyclase Coupling Protein in Pseudohypoparathyroidism
Z Farfel, AS Brickman, HR Kaslow, VM Brothers, HR Bourne |
New England Journal of Medicine | 1980 |
The syndromes of primary hormone resistance
GF Verhoeven, JD Wilson |
Metabolism | 1979 |
Contemporary Metabolism
N Freinkel |
1979 | |
Physiology of Membrane Disorders
TE Andreoli, JF Hoffman, DD Fanestil |
1978 |