Thyroid hormone regulation of beta-adrenergic receptors and catecholamine sensitive adenylate cyclase in foetal heart.
The effect of thyroid hormone on the beta-adrenergic receptor in foetal cardiac membranes was analysed by measuring the binding of (-)[3H]DHA. The specific activities (per mg protein) of beta-adrenergic receptors decreased with advancing gestational age, whereas the total activities (per heart) increased under the similar conditions. The change in the binding affinities was not statistically significant. 1; 3,5,3'-L-triiodothyronine (T3) stimulated the (-)[3H]DHA binding capacities of the cardiac membranes of foetuses of all age groups. The enhancement in the receptor activity was completely inhibited actinomycin D or cycloheximide. The contents of epinephrine, norepinephrine and cAMP increased with advancing gestational age; but T3 had no significant effect on the catecholamines or cAMP. Similarly, the activities of the basal, NaF stimulated and Gpp(NH)p stimulated adenylate cyclase remained unaltered by T3, but the activities increased progressively with foetal maturity. The absolute values of catecholamine stimulated adenylate cyclase activities in the hearts of T3 treated foetuses were, however, higher compared to those in the untreated foetuses. The enhancement of the activities were totally blocked by the action of actinomycin D, cycloheximide or propranolol. Our results indicate that thyroid hormone enhances the number of beta-adrenergic receptor binding sites by synthesizing new receptor proteins resulting in increased catecholamine sensitivity.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005318:Fetal Heart / Q000201:enzymology / Q000378:metabolism*; D005865:Gestational Age; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine