AGE-RELATED ALTERATIONS IN PULSATILE SECRETION OF TSH - ROLE OF DOPAMINERGIC REGULATION

To investigate the influence of aging on dopaminergic modulation of pulsatile thyrotropin (TSH) secretion, we examined changes in circulating TSH levels during the day and night with and without a dopamine antagonist metoclopramide, in healthy young (20-35 yr old) and old (69-83 yr old) subjects, with the use of cluster analysis. Baseline thyroid function tests including serum thyroxine, 3,5,3' -triiodothyronine (T3), T3 resin uptake, and TSH and the response of TSH to thyrotropin-releasing hormone were within normal limits in young and old subjects, and antimicrosomal and anti-thyrogloublin antibodies were absent in all participants. Pulsatile TSH secretion was indentified in all subjects, and as a group there were significant increases in nocturnal peak height (P < 0.01), amplitude (P < 0.01), and mean TSH (P < 0.001). TSH pulse amplitude increased 160% (P < 0.05) at night compared with day in the young but was unchanged at night in the old. After the administration of metoclopramide there was a significant increase in peak height (P < 0.01), amplitude (P < 0.01), and mean TSH (P < 0.01). However, the effect of metoclopramide was different in young and old subjects. In the young, daytime administration of metoclopramide increased TSH pulse height (P < 0.02) and mean TSH (P < 0.05); pulse parameters remained unchanged at night. In comparison, in old subjects after metoclopramide, pulse parameters were unchanged during the day but pulse amplitude significantly (P < 0.01) increased at night. TSH pulse frequency remained stable with age and was unaltered after metoclopramide. We conclude that TSH pulsatile secretion is preserved in elderly men but blunted at night. The mechanisms for this alteration in pulsatile TSH secretion may be due to age-associated changes in day-night dopaminergic regulation.