Beta 2 receptor-mediated stimulation of Friend erythroleukemia cell growth by thyroid hormones.

Thyroid hormones are known to enhance normal erythroid colony growth (CFUE) and this enhancement depends on a functional beta 2-adrenergic receptor mechanism. we investigated the response of Friend cells to thyroid hormones, catecholamines, and other compounds influencing cellular cAMP activity. The thyroid hormones L-T3, L-T4, and "reverse T3" stimulated erythroleukemia colony growth in a serum-substituted methylcellulose culture system with peak activity at 10(-7) M. Various beta-adrenergic compounds enhanced Friend leukemia colony growth; however, the alpha-adrenergic agonist phenylephrine was inactive. Dibutyryl cyclic AMP and the phosphodiesterase inhibitor theophylline also enhanced Friend leukemia colony formation. Adrenergic antagonists with beta 2 specificity abrogated the stimulatory effect of L-T3, L-T4, and of "reverse T3" at equimolar concentrations. These experiments demonstrate that thyroid hormones, beta-adrenergic agonists, the phosphodiesterase inhibitor theophylline, and dbcAMP have a direct effect on the proliferation of Friend erythroleukemia cells. We conclude that thyroid hormones' action requires a functioning beta 2-adrenergic receptor mechanism. Thyroid hormones directly modulate the growth of neoplastic erythroid cells in a manner consistent with their effects on normal erythropoiesis.