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Short-Term Effects of Thyroid Hormones and 3,5-Diiodothyronine on Membrane Transport Systems in Chick Embryo Hepatocytes

Department of Biology (S.I.), University of Rome ‘Roma Tre,’ 00146 Rome, Italy; Department of Biology (P.D.V., P.L.), University of Rome ‘Tor Vergata,’ 00133 Rome, Italy; and Department of Cellular and Developmental Biology (S.S., S.L.), University of Rome ‘La Sapienza,’ 00185 Rome, Italy

Address all correspondence and requests for reprints to: Prof. Sandra Incerpi, Department of Biology, University of Rome ‘Roma Tre,’ Viale Marconi 446, 00146 Roma, Italy. E-mail: . incerpi{at}uniroma3.it

Rapid nongenomic effects of thyroid hormones L-T₃ and L-T₄ on two plasma membrane transport systems were investigated in 14-d-old and 19-d-old chick embryo hepatocytes. The Na⁺/H⁺ exchanger activity was measured using the intracellular pH-sensitive fluorescent probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester, whereas the amino acid transport was estimated by [1-¹⁴C]-2-aminoisobutyric acid uptake. System A amino acid transport activation was linear to hormone concentration, whereas the Na/H exchanger gave a bell-shaped dose-response curve, with a maximum at the physiological hormone concentration of 1 nM. The specificity of the effect was verified by the use of inhibitors and analogues. The thyroid hormone analog 3,5-diiodo-L-thyronine was able to mimic some of the hormone effects, but with a lower efficiency. The effect on the Na⁺/H⁺ exchanger was identified for 14-d-old and 19-d-old cells, whereas the amino acid transport could only be activated at the late stage of embryo development. Both transport systems were activated through a signal transduction pathway involving PKC, MAPK pathway, and PI3K, even though the differences in response behavior indicate a differential modulation of the two transport systems by L-T₃ and L-T₄. These results clearly demonstrate the existence of rapid nongenomic action of thyroid hormones also in avian cells, and show that activation of System A amino acid transport is not directly correlated to changes in intracellular pH. For the first time, evidence is presented which suggests that short-term effects of thyroid hormones may play a role during fetal development and cell differentiation.

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