Modulation by catecholamines and thyrotrophin of cyclic AMP response to beta-adrenergic stimulation by cultured...

Thyroid cell cyclic AMP synthesis is stimulated by beta-adrenergic agonists. We have characterized this sensitivity on cultured porcine thyroid cells and have studied its modulation by chronic treatment with thyrotrophin. The synthesis of cyclic AMP in intact porcine thyroid cells in primary culture was stimulated by the beta-adrenergic agonist, isoproterenol. This stimulation was dose-dependent and was inhibited by the beta-adrenergic antagonists propranolol and alprenolol. The cell responsiveness (i.e. the response elicited by 5 microM-isoproterenol after 5-min stimulation) was increased when the cells were cultured in the absence of thyrotrophin. Thyrotrophin, when present in the culture medium at the onset of culturing, inhibited this increase. A concentration of 100 microunits. thyrotrophin/ml was sufficient to reduce the cyclic AMP response to 15% of its control value. Prostaglandin E2 or dibutyryl cyclic AMP did not mimic the effect of thyrotrophin. The low sensitivity of thyrotrophin-treated cells to beta-adrenergic agonists could be explained by a decreased number of beta-adrenergic receptors. [125I]Iodohydroxybenzyl pindolol specific binding was ten times greater in membrane preparations of control cells than in membranes derived from thyrotrophin-treated cells. The beta-adrenergic sensitivity of cultured thyroid cells was also decreased after long-term treatment by terbutaline. A time- and dose-dependent desensitization was observed.