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

Abstract

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.

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”

“…The chick embryo hepatocytes respond to T 3 with a very rapid, but transient, decrease in Na ϩ -K ϩ -ATPase activity, followed by an increase in Na/H exchanger activity. In the present report, Scapin et al (18) showed that T 3 transiently inhibited Na ϩ -K ϩ -ATPase activity in chick embryo hepatocytes at 14 and 19 days, with more potent, but shorterlived, inhibition in the embryonic day 19 cells. The day 19 hepatocytes had almost twofold more basal Na ϩ -K ϩ -ATPase activity (without T 3 ) than the day 14 cells.…”

Intracellular and plasma membrane-initiated pathways involved in the [Ca2+]ielevations induced by iodothyronines (T3 and T2) in pituitary GH3cells

“…Some of these actions lead rapidly to posttranslational modifications of nucleoproteins, including MAPK-mediated serine phosphorylation of the thyroid hormone receptor (13), estrogen receptor (52), and p53 (49). In addition, upstream of MAPK, PKC and phosphatidylinositol 3-kinase (PI3-K) pathways may also be activated by thyroid hormones (42).…”

Maternal-Fetal Thyroid Interactions

“…about the developmental thyroid hormone mechanisms (deiodinases, transporters, sulfotransferases and receptors) in human [1,2,50,52,127,130,[151][152][153][154], rat [1,2,41,60,135,[154][155][156] and chicken [7,[157][158][159][160][161][162][163][164][165][166][167][168][169][170]. Note that the chicken is born early compared to the rat and human, as well as the rat is born early compared to the human (Table 6).…”