A B S T R A C T We have previously demonstrated that 3,5,3'-triiodothyronine (T3), whether administered in vivo or added to suspending media in vitro, promptly stimulates the in vitro accumulation of the nonmetabolized amino acids, alpha-aminoisobutyric acid, and cycloleucine (CLE) by thymocytes isolated from weanling rats. In these studies, we have examined the in vitro interaction between catecholamines and T3 with respect to this effect. The previously reported enhancement of CLE accumulation in thymocytes by T3 in vitro (1 ,uM) was confirmed. When added alone in concentrations ranging between 10 nM and 0.1 mM, the adrenergic agonists, epinephrine and norepinephrine, had no effect on CLE accumulation. At a concentration of 1 ,uM, isoproterenol, terbutaline, and phenylephrine were also without effect. However, the effect of T3 was clearly potentiated by the concomitant addition of epinephrine, norepinephrine, and possibly isoproterenol, whereas terbutaline and phenylephrine were without effect. Neither basal nor T3-enhanced CLE accumulation was affected by the addition alone of the adrenergic blocking agents, propranolol (0.1 mM), phentolamine (10 ,uM), or practolol (0.1 mM). Nevertheless, the beta1-and beta2-antagonist, propranol, and the beta,-antagonist, practolol, blocked the increment in CLE accumulation produced by epinephrine; the alpha-antagonist, phentolamine, was without effect.The enhancement of CLE accumulation that occurred in the presence of T3, with or without epinephrine, was seen to be a result of an inhibition of CLE efflux, because T3 alone inhibited CLE efflux, and this effect was increased when epinephrine was also present. On This study was presented in part at The Eighth Annual Meeting of the European Thyroid Association, Lyon, France, October 1977.Received for publication 21 July 1978 and in revised form 6 December 1978. 1172 the other hand, neither T3 alone nor T3 plus epinephrine appreciably altered the rate of inward transport of CLE. As judged from studies of the ability ofthymocytes to exclude trypan blue, neither T3 alone nor T3 plus epinephrine either enhanced or impaired viability of cells during 3-h periods of incubation. Cell water content, measured with [3H]urea, was unaffected by T3, either alone or in the presence of epinephrine. In confirmation of previous results, the stimulatory effect ofT3 on CLE accumulation was unaffected by concentrations of puromycin sufficient to inhibit protein synthesis by at least 95%, and the potentiating action of epinephrine on the response to T3 was similarly unaffected. From these findings, it is concluded that the effect of T3 to increase CLE accumulation by thymocytes in vitro, though itselfindependent ofadrenergic mediation, is potentiated by beta1-adrenergic stimulation. This interaction appears distinctly different from other thyroid hormone-catecholamine interactions, in which thyroid hormones enhance physiological responses to catecholamines. Its mechanism remains unclear, but the properties of the T3 effect, and possibly the inte...

In previous studies, we have demonstrated that 3,5,3'-triiodothyronine (T3), either added to suspended media in vitro or injected acutely in vivo, increases the in vitro accumulation of the non-metabolized amino acid cycloleucine (CLE) by thymocytes harvested from weanling rats. We now report that this reponse is greatly enhanced by prior adrenalectomy of the donor rat. In vitro, a significant increase in CLE accumulation in thymocytes from adrenalectomized rats was induced by T3 at a concentration of 1 x 10-10 M, while a concentration of 1 x 10-6 M was required to produce a similar and significant effect in thymocytes from intact animals. In adrenalectomized animals, a single iv dose of T3 (0.5 microgram/100 G bw) significantly increased the in vitro accumulation of CLE in thymocytes harvested two hours later. In contrast, ten-times that dose was ineffective in control animals. Increased sensitivity to T3 was abolished by physiological replacement doses of hydrocortisone. The data are consistent with the well-known opposing effects of physiological levels of thyroid and glucocorticoid hormones on the growth and function of lymphoid tissue in vivo and, together with other findings, suggest that thyroid hormones modulate the cellular accumulation of amino acids in the intact animal.