The interactions between the β-adrenergic system and thyroid hormone
(T3) on cardiac function have been investigated in detail.
In addition to β-adrenoceptors, α1-adrenergic receptors
are present in ...the mammalian heart. The interactions between
T3 and the α1-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 anα
1-adrenergic agonist. We demonstrate that direct
activation of the α1-adrenergic signaling pathway, using
a mutant constitutively active G protein (Gq) 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 α1-adrenergic stimulation. These results
suggested that activation of the α1-adrenergic signaling
pathway has an inhibitory effect on T3-dependent SERCA2
gene transcription. As this inhibitory effect ofα
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.
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