Immune-neuroendocrine interactions during aging: Age-dependent thyrotropin-inhibiting activity of thymosin peptides

Abstract

Thymosin fraction 5 (TF-5), a partially purified thymic preparation, has been previously shown to have luteinizing hormone-releasing hormone (LH-RH)-releasing activity in perfused rat hypothalamus as well as in vivo stimulatory effect on the pituitary-adrenal axis in prepubertal monkeys. We report here the effect of TF-5 on the TSH-thyroid axis in young (3 months) and old (25 months) Sprague-Dawley male rats. Conscious free-moving animals carrying an indwelling atrial cannula received a single dose of 5 mg/kg body wt. of either bovine serum albumin (BSA) or TF-5 via the cannula. In the young rats, TF-5 induced a marked reduction of plasma thyrotropin (TSH) which was significantly greater than the normal circadian decline observed in the BSA-treated controls. The old males displayed high basal levels of TSH which showed no circadian rhythmicity, and did not respond to TF-5. Thyroxine (T 4), triiodothyronine (T 3), corticosterone, and prolactin levels were not affected by TF-5 at the dose levels tested. The old rats had significantly lower basal levels of T 4, but not T 3, than their young counterparts. The synthetic peptides thymosin α-1 and serum thymic factor, which are components of TF-5, had no effect on the above hormones when injected in doses up to 5 μg/kg body wt. Acute thymectomy in 3-month-old males induced a significant increase in basal levels of TSH without affecting plasma T 4 or T 3. These results suggest that the thymus has an inhibitory action on TSH in the rat, which is not mediated by the thyroid gland. Our results also suggest an age-related desensitization of the TSH system to thymic influence in this species.