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.
D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004920:Erythropoiesis / Q000187:drug effects; D005622:Friend murine leukemia virus; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology*
D002395:Catecholamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D013963:Thyroid Hormones; D002078:Butoxamine