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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Short-term effects of thyroid hormones on Na⁺-K⁺-ATPase activity of chick embryo hepatocytes during development: focus on signal transduction

Departments of ¹Cellular and Developmental Biology, and ²Physiology and Pharmacology Vittorio Erspamer, Sapienza University of Rome, Rome; and ³Department of Biology, University of Rome "Roma Tre," Rome, Italy

Submitted 7 December 2007 ; accepted in final form 26 September 2008

Nongenomic effects of thyroid hormones on Na⁺-K⁺-ATPase activity were studied in chick embryo hepatocytes at two different developmental stages, 14 and 19 days of embryonal age, and the signal transduction pathways involved were characterized. Our data showed the following. 1) 3,5,3'-Triiodo-L-thyronine (T₃) and 3,5-diiodo-L-thyronine (3,5-T₂) rapidly induced a transient inhibitory effect on the Na⁺-K⁺-ATPase; the extent and duration depended on the developmental age of the cells. 2) 3,5-T₂ behaved as a true hormone and fully mimicked the effect of T₃. 3) Thyroxine had no effect at any of the developmental stages. 4) The inhibition of Na⁺-K⁺-ATPase was mediated by activation of protein kinase A, protein kinase C, and phosphoinositide 3-kinase, suggesting several modes of modulation of ATPase activity through phosphorylation at different sites. 5) The MAPK pathway did not seem to be involved in the early phase of hormone treatment. 6) The nonpermeant analog T₃-agarose inhibited Na⁺-K⁺-ATPase activity in the same way as T₃, confirming that hormone signaling initiated at a receptor on the plasma membrane. From these results, it can be concluded that the cell response mechanisms change rapidly and drastically within the early phase of embryo growth. The differences found at the two stages probably reflect the different roles of thyroid hormones during development and differentiation.

3,5-diiodothyronine; 3,5,3'-triiodothyronine; protein kinase A; protein kinase C; phosphoinositide 3-kinase

This article has been cited by other articles:

				J. Lei, M. Bhargava, and D. H. Ingbar Cell-specific signal transduction pathways regulating Na+-K+-ATPase. Focus on "Short-term effects of thyroid hormones on the Na+-K+-ATPase activity of chick embryo hepatocytes during development: focus on signal transduction" Am J Physiol Cell Physiol, January 1, 2009; 296(1): C1 - C3. [Full Text] [PDF]