Thyroid hormone regulation of membrane Ca2(+)-ATPase activity

The Ca2(+)-ATPase of plasma membranes from a variety of tissues is subject to stimulation in vitro, and apparently in vivo, by physiological concentrations of iodothyronines regarded as biologically active in other bioassay systems. This calmodulin-dependent action of thyroid hormone is nongenomic, that is, directly on the cell membrane and independent of the cell nucleus. In the case of human erythrocyte Ca2(+)-ATPase, this assay of thyroid hormone bioactivity is attractive as an in vitro, readily-studied model of hormone action in a human cell. Enzyme activity is paralleled, as expected, by changes in calcium pump activity. Thyroid hormone action in this system is subject to modulation by glucose and by a variety of compounds which, like iodothyronines, are hydrophobic. The mechanism of thyroid hormone action on membrane Ca2(+)-ATPase involves, at least in part, membrane lipids, including components of the phosphatidylinositol cycle. The physiologic role of thyroid hormone action on cell membrane Ca2(+)-ATPase is speculative. In plasma membranes of nonexcitable and excitable tissues, ambient thyroid hormone may set basal activity of Ca2(+)-ATPase or magnitude of the enzymatic response to calmodulin Ca2+.