Effects of diabetes on rodent cardiac thyroid hormone receptor and
isomyosin expression.
Haddad, F., P. W. Bodell, S. A. McCue, and K. M. Baldwin.
Department of Physiology and Biophysics, University of California,
Irvine, Irvine, California 92717
APStracts 4:0016E, 1997.
Previous studies show that diabetes induces marked transformations in
cardiac myosin heavy chain (MHC) gene expression that is somehow
linked to the cellular action of thyroid hormone (T3). In this study,
we tested the hypothesis that diabetes induces a reduced expression
of thyroid hormone receptors (TRs), which are known to be important
transcription factors interacting with thyroid response elements
(TREs) in the promoter region of both (- and (-MHC genes. Adult
female rats were randomly assigned to either a normal control (NC) or
diabetic (D) group. Three and/or six weeks after induction of
diabetes via streptozotocin injection, the hearts were analyzed for
MHC and TR mRNA isoforms expression, nuclear T3 binding, and nuclear
extract interaction with a palindromic TRE. Results showed that
diabetes induced significant alteration in (- and (-MHC expression.
Northern blot analyses indicated no diabetes associated differences
in TR isoform mRNA signals. Cardiac nuclear T3 binding studies
suggested no differences in either the binding capacity (Bmax) or the
equilibrium binding constant (Kd) among the two groups, indicating no
changes in either the number of nuclear TRs or their affinity for T3.
Furthermore, gel mobility shift assays detected no difference between
NC and D groups for cardiac nuclear extract binding to palindromic
TRE. Collectively, these findings suggest that while diabetes exerts
a profound effect on cardiac isomyosin gene expression, the
underlying mechanism, while dependent on factors linked to T3
function, does not involve alterations in TR expression.
Received 3 September 1996; accepted in final form 8 January 1997.
APS Manuscript Number E438-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997