This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, P. S.-C. Articles by Dillmann, W. H. Search for Related Content PubMed PubMed Citation Articles by Wu, P. S.-C. Articles by Dillmann, W. H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LIOTHYRONINE

₁-Adrenergic Stimulation Inhibits 3,5,3'-Triiodothyronine-Induced Expression of the Rat Heart Sarcoplasmic Reticulum Ca²⁺ Adenosine Triphosphatase Gene¹

Department of Medicine, Divisions of Endocrinology (P.S.W., A.S.M., H.H., W.H.D.), Cardiology (K.U.K.), and Pharmacology (R.H.-D.), University of California-San Diego, La Jolla, California 92093-0618

Address all correspondence and requests for reprints to: Wolfgang H. Dillmann, M.D., Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093-0618.

The interactions between the ß-adrenergic system and thyroid hormone (T₃) on cardiac function have been investigated in detail. In addition to ß-adrenoceptors, ₁-adrenergic receptors are present in the mammalian heart. The interactions between T₃ and the ₁-adrenergic system remain, however, poorly understood. T₃ stimulates the expression and transcription of the sarcoplasmic reticulum Ca²⁺ adenosine triphosphatase (SERCA2) gene, a protein vital in the control of cardiac calcium transients and contractility. We show that in rat cardiac myocytes, the stimulatory effect of T₃ on SERCA2 messenger RNA expression and gene transcription is inhibited by an ₁-adrenergic agonist. We demonstrate that direct activation of the ₁-adrenergic signaling pathway, using a mutant constitutively active G protein (G_q) similarly down-regulated the T₃ effect on SERCA2 transcription. The combined effect of thyroid hormone receptor and retinoid X receptors on T₃-stimulated SERCA2 gene transcription was also markedly attenuated by ₁-adrenergic stimulation. These results suggested that activation of the ₁-adrenergic signaling pathway has an inhibitory effect on T₃-dependent SERCA2 gene transcription. As this inhibitory effect of ₁-adrenergic stimulation occurs when only one thyroid hormone response element (TRE) drives reporter expression, it is most likely mediated by an alteration of the nuclear factors binding to the TRE or by influencing the interaction of the TRE complex with the basal transcriptional machinery.

This article has been cited by other articles:

				G. J. Kahaly and W. H. Dillmann Thyroid Hormone Action in the Heart Endocr. Rev., August 1, 2005; 26(5): 704 - 728. [Abstract] [Full Text] [PDF]

				P. D. Ho, J.-S. Fan, N. L. Hayes, N. Saada, P. T. Palade, C. C. Glembotski, and P. M. McDonough Ras Reduces L-Type Calcium Channel Current in Cardiac Myocytes : Corrective Effects of L-Channels and SERCA2 on [Ca2+]i Regulation and Cell Morphology Circ. Res., January 19, 2001; 88(1): 63 - 69. [Abstract] [Full Text] [PDF]

				B. Gloss, S. Villegas, F. J. Villarreal, A. Moriscot, and W. H. Dillmann Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca2+ ATPase gene is inhibited by LIF and IL-6 Am J Physiol Endocrinol Metab, April 1, 2000; 278(4): E738 - E743. [Abstract] [Full Text] [PDF]

				R. E. Weiss, Y. Murata, K. Cua, Y. Hayashi, H. Seo, and S. Refetoff Thyroid Hormone Action on Liver, Heart, and Energy Expenditure in Thyroid Hormone Receptor {beta}-Deficient Mice Endocrinology, December 1, 1998; 139(12): 4945 - 4952. [Abstract] [Full Text] [PDF]

				P. D. Ho, D. K. Zechner, H. He, W. H. Dillmann, C. C. Glembotski, and P. M. McDonough The Raf-MEK-ERK Cascade Represents a Common Pathway for Alteration of Intracellular Calcium by Ras and Protein Kinase C in Cardiac Myocytes J. Biol. Chem., August 21, 1998; 273(34): 21730 - 21735. [Abstract] [Full Text] [PDF]