Effects of thyroid hormones on cardiac hypertrophy and beta-adrenergic receptors during aging

Administration of thyroxine daily at a dosage of 6.4 mu g/g body weight stimulates cardiac hypertrophy in both 9--13-month-old (mature, n = 34) and 22--24-month-old (senescent, n = 45) Wistar rats. The increase due to thyroxine as well as the time course of the effect do not change with age, although ventricular wet weight to tibial length ratios are higher in senescent animals at 0, 3, and 7 days of treatment (senescent controls = 0.331; senescent hypertrophied = 0.395; mature controls = 0.295; mature hypertrophied = 0.336). Hypertrophy is maximal after 3 days. beta-Adrenergic receptor levels as measured by stereospecific binding of dihydroalprenolol in mature rats are increased about two-fold after 7 days of thyroxine treatment (mature controls = 35 +/- 3 fmol/mg protein, mature treated = 65 +/- 6 fmol/mg protein). Although both stimulated and control values do not differ significantly between mature and senescent groups (senescent controls = 45 +/- 4 fmol/mg protein, senescent treated = 56 +/- 9 fmol/mg protein), the effect of thyroxine on senescent hearts is not statistically significant. In addition, 3-day levels do not increase over 0-day controls at either age. No significant differences in either beta-adrenergic receptor concentrations or affinities between age groups are observed at 0, 3, and 7 days of treatment. However, senescent membrane preparations contain 33% more sialic acid (a rough plasma membrane marker) per unit of protein than mature preparations. Thus, the beta-adrenergic receptor density per unit of sialic acid may be reduced very slightly in the senescent hearts.