Glycogenolytic responsiveness to glucagon, epinephrine, vasopressin and angiotensin II in the liver of developing hypothyroid rats. A comparative study of in vitro hormonal binding and in vivo biological response.
Both dose-response curves and time-courses of plasma glucose levels after single maximal doses showed that in vivo glycogenolytic responsiveness to glucagon and epinephrine was significantly higher in developing hypothyroid rats, whereas it remained unchanged after vasopressin and angiotensin II injections. In contrast with the decreased basal activity of phosphorylase(a), the glucagon-stimulated activity increased in hypothyroid rats, whereas it was only slightly modified under vasopressin stimulation. Daily thyroxine treatment abolished these abnormalities. Thus, there is a close correlation between glucose output and enzyme activation. The maximal binding capacity of [3H]vasopressin and [125I]glucagon was significantly decreased in hypothyroid rats, without changes in the apparent dissociation constant of hormone from its specific receptor. Daily thyroxine treatment also abolished this deficit, which moreover appeared to be independent of possible changes in plasma hormone levels. With respect to glucagon action, neither basal nor Gpp(NH)p-stimulated adenylate cyclase activities were affected in hypothyroid rats. Glucagon-sensitive adenylate cyclase activity and the apparent activation constant appeared to be unaffected. The apparent discrepancy between the results obtained from in vivo and in vitro experiments is discussed on the basis of different membrane transducing phenomena and related intracellular mechanisms underlying the biological response to hormonal stimulation.
Ali
M
M
UA 1197 du CNRS Neurobiologie Endocrinologique, Université des Sciences et Techniques, Languedoc, Montpellier, France.
Cantau
B
B
Clos
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000502:physiology; D005260:Female; D005934:Glucagon / Q000378:metabolism / Q000502:physiology; D007037:Hypothyroidism / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000378:metabolism / Q000502:physiology
D001786:Blood Glucose; D008112:Liver Glycogen; D014667:Vasopressins; D000804:Angiotensin II; D005934:Glucagon; D010762:Phosphorylase a; D006005:Phosphorylases; D000262:Adenylyl Cyclases; D004837:Epinephrine