HORMONAL REGULATION OF GROWTH AND DIFFERENTIATION

Hormone-receptor interactions and the role of these interactions in the endocrine regulation of ion fluxes in target tissues will continue to be examined in both the avian erythrocyte and in mammalian liver and muscle with specific reference to the catecholamine and thyroid hormones. Studies in the turkey erythrocyte are designed to further characterize the mechanism by which low concentrations of beta-adrenergic agents induce a very large and virtually instantaneous increase in bi-directional sodium and potassium fluxes; the nature of the pathway by which these changes in fluxes are mediated; and the means by which changes in thyroid status induce their demonstrated effects on the catecholamine responsiveness of the normal cell. Other studies will continue work begun during the present project period on rat liver and diaphragm with the objective of defining the physiologic role of the catecholamine and thyroid hormones in the regulation of cation fluxes in these more complex mammalian tissues. Objectives of these latter studies will include a detailed characterization of the mechanism by which beta-adrenergic agents induce prompt and striking changes in both the uptake and release of monovalent cations in vitro; an examination of the physiologic role of these hormonally induced changes with particular regard to their modulation of the extracellular potassium ion concentration; and a detailed investigation of mechanisms of thyroid thermogenesis with special reference to the possibility that the thermogenic effect of the thyroid hormones, rather than being attributable to a primary induction of an increased number of active cation pump units per se, instead results from a more proximal hormone-induced increase in the permeability of the cell to the passive leak of sodium and potassium ions. The recent demonstration that a marked increase in cell permeability is demonstrable in rat liver as early as six hours after a single injection of T3, and that this change actually precedes any reported change in active pump unit number, now makes it possible to test such an hypothesis directly.