Thyroid hormone (T3) exerts its primary genomic effects via nuclear receptors. Which isoform of thyroid receptor (TR) has the highest affinity for T3 and is predominantly expressed in cardiac tissue?

• A TRβ1; predominantly expressed in the liver and kidney
• B TRα1; predominantly expressed in cardiac and skeletal muscle, mediating chronotropic and inotropic effects ✓
• C TRβ2; predominantly in the pituitary and hypothalamus mediating negative feedback
• D TRα2; the dominant isoform in the heart with highest T3 affinity

Explanation

TRα1 (thyroid receptor alpha-1) is the principal TR isoform in the heart and skeletal muscle. In cardiac myocytes, T3 binding to TRα1 upregulates alpha-myosin heavy chain (fast, high-ATPase), sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and the Na+/K+-ATPase while downregulating phospholamban and beta-myosin heavy chain — collectively increasing heart rate and contractility. This is why hyperthyroidism causes tachycardia and high-output state. TRβ1 mediates hepatic metabolic effects; TRβ2 mediates pituitary T3 feedback for TSH suppression. TRα2 does not bind T3 (it is a dominant negative splice variant).

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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