Short-term effects of thyroid hormones and 3,5-diiodothyronine on membrane transport systems in chick embryo hepatocytes

Endocrinology. 2002 May;143(5):1660-8. doi: 10.1210/endo.143.5.8767.

Abstract

Rapid nongenomic effects of thyroid hormones L-T(3) and L-T(4) 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-(14)C]-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-T(3) and L-T(4). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Biological Transport, Active / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chick Embryo
  • Diiodothyronines / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Hydrogen-Ion Concentration
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Signal Transduction / drug effects
  • Sodium-Hydrogen Exchangers / metabolism
  • Thyroid Hormones / pharmacology*

Substances

  • Amino Acids
  • Diiodothyronines
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Sodium-Hydrogen Exchangers
  • Thyroid Hormones
  • 3,5-diiodothyronine
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases