Nuclear thyroid hormone binding activities and serum iodothyronine levels in aging rats

Since aging mammals present a spectrum of physiologic conditions that mimic the hypothyroid state, we measured serum thyroid hormone levels and the maximum binding capacities and affinities of solubilized nuclear thyroid hormone binding proteins from liver, kidney, heart and cerebellum in healthy male and female Wistar rats of various postpubertal ages (3–4, 7–8, 15–17 mo; 12 rats/group). In cross-sectional measurements, serum levels of T₃ increased by about 40% (3 mo to 15 mo) in both males and females; T₄ levels increased in males by 22% but decreased slightly in females. The affinity of T₃ and T₄ binding to nuclear receptors was highly conserved between tissues, male vs female and with age (mean ± SE: T₃ K_d = 0.90±0.4 × 10⁻¹⁰M; T₄ K_d = 6.02±0.28 × 10⁻¹⁰M). However, maximum binding capacity in the heart decreased significantly by 15 mo for T₃ (−60% in male, −46% in female) and T₄ (−58% in males and −45% in females). Cerebellum showed a pattern similar to the heart in loss of binding capacity with males showing a 56% decrease and females showing a 53% decrease in nuclear T₃ binding activity. A trend toward decreased cerebellar T₄ binding in the 3–15 mo period missed significance for males and females. By contrast, hormone binding in liver and kidney generally increased through 15 mo of age for both T₃ and T₄. We conclude that certain tissues containing mitostatic cells (heart and cerebellum) may selectively lose nuclear thyroid hormone receptors during post-pubertal aging.