Developmental changes in regulation of the Na+, K(+)-ATPase alpha 3 isoform by thyroid hormone in ferret heart.
Ferret heart expresses the alpha 1- as well as the alpha 3-isoform of the Na+, K(+)-ATPase. We have shown previously that the alpha 3 isoform is differentially upregulated during postnatal cardiac development and that in adult ferrets expression of alpha 3 is not responsive to regulation by thyroid hormone (TH). Since developmental-stage dependent effects of TH have been reported previously, the present study examined whether effects of TH on expression of the Na+, K(+)-ATPase isoforms in ferret heart is modulated during development and possible mechanisms were examined. Ferrets of different age groups were treated with TH and the relative abundance of Na+, K(+)-ATPase isoforms in ferret myocardium was determined by immunoblotting. Thyroid hormone (T3; 50 micrograms/100 g body weight on 3 alternating days, s.c.) increased protein levels of the alpha 3 isoform, but not that of alpha 1 or beta 1, in myocardium of 5-day-old and 3-week-old ferrets. By contrast, in myocardium of 6- and 8-week-old ferrets T3 failed to increase protein levels of alpha 1 and alpha 3. To determine whether elevated plasma levels of TH during development plays a role in the transition, mature ferrets were first made hypothyroid before TH treatment. In these hypothyroid ferrets expression of the alpha 3 isoform remained unresponsive to TH (T4, 0.5 mg/kg for 7 days, s.c.). The transition from TH-responsive to TH-unresponsive appears to be isoform-specific because in skeletal muscle of 8-week-old ferrets and in hypothyroid ferrets the alpha 2 isoform is upregulated by TH. Finally, there appears to be functional thyroid hormone receptors throughout development because in each age group TH effectively induced expression of alpha-MHC in the myocardium. In conclusion, these findings demonstrate that expression of alpha 3 isoform in the myocardium of newborn ferret is responsive to TH; however, the responsiveness terminates between 3- and 6-weeks of age. Neither elevated endogenous TH level nor a lack of functional thyroid hormone receptor appears to be responsible for the transition from TH-responsive to TH-unresponsive.
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Department of Pharmacology, College of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
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D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005289:Ferrets; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006980:Hyperthyroidism / Q000201:enzymology; D007037:Hypothyroidism / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000502:physiology*
D007527:Isoenzymes; D013963:Thyroid Hormones; D000254:Sodium-Potassium-Exchanging ATPase