CARRIER-MEDIATED TRANSPORT OF THYROID HORMONE INTO RAT HEPATOCYTES IS RATE-LIMITING IN TOTAL CELLULAR UPTAKE AND METABOLISM

Abstract

We investigated if carrier-mediated transport into rat hepatocytes is rate-limiting in total cellular uptake and metabolism of thyroid hormone. Rat hepatocytes in primary monolayer culture were incubated under equilibrium conditions with tracer T4, T3 or rT3 in the absence or presence of inhibitors of thyroid hormone uptake, i.e., ouabain and ER-22, a monoclonal antibody against the rat hepatocyte plasma membrane. The results for all three iodothyronines show that inhibition of clearance from the medium during incubation is paralleled by a similar decrease in iodide production. This indicates that the decrease in metabolism of thyroid hormone is directly related to the inhibition of cellular uptake. These findings underline the potential importance of the plasma membrane in the regulation of thyroid hormone metabolism and, therefore, determination of expression of thyroid hormone activity.