MODULATION BY THYROID STATUS OF CYCLIC AMP-DEPENDENT AND CA-2+-DEPENDENT MECHANISMS OF HORMONE ACTION IN RAT-LIVER CELLS - POSSIBLE INVOLVEMENT OF 2 DIFFERENT TRANSDUCTION MECHANISMS IN ALPHA-1-ADRENERGIC ACTION

The actions of hormones which are associated to cAMP-dependent and Ca-dependent mechanisms of signal transduction were studied in hepatocytes obtained from rats with different thyroid states. In cells from euthyroid and hyperthyroid rats, the metabolic actions of epinephrine were mediated mainly through .alpha.1-adrenoceptors; .beta.-adrenoceptors seem to be functionally unimportant. Both .alpha.1- and .beta.-adrenoceptors mediate the actions of epinephrine in hepatocytes from hypothyroid animals. Phosphatidylinositol labeling was strongly stimulated by epinephrine, vasopressin and angiotensin II in cells from eu-, hyper- or hypothyroid rats. Metabolic responsiveness to vasopressin and angiotensin II was markedly impaired in the hypothyroid state. The glycogenolytic response to the Ca ionophore A-23187 was also impaired, suggesting that hepatocytes from hypothyroid rats are less sensitive to Ca signalling. The persistence of .alpha.1-adrenergic responsiveness in the hypothyroid state suggests that the mechanism of signal transduction for .alpha.1-adrenergic amines is not identical to that of vasopressor peptides. .alpha.1-Adrenergic stimulation of cAMP accumulation was not detected in cells from hypothyroid rats. Factors besides Ca and besides cAMP are probably involved in .alpha.1-adrenergic actions. Metabolic responses to glucagon and to the cAMP analog dibutyryl cAMP were not markedly changed during hypothyroidism, although cAMP accumulation produced by glucagon and .beta.-adrenergic agonists was enhanced. In hyperthyroidism, cell responsiveness to epinephrine, vasopressin, angiotensin II and glucagon was decreased, but sensitivity to cAMP was not markedly altered. The factors involved in this hyposensitivity to hormones during hyperthyroidism are unclear.