The effect of thyroid hormones in vitro and in vivo on hypothalamic neurotensin release and content.

Neurotensin (NT) is a hypothalamic peptide which inhibits TSH secretion when administered intraventricularly to the rat. We have studied the effects of TRH, TSH, T3, and rT3 on the release of immunoreactive NT (iNT) from incubations of freshly dissected sections of whole hypothalamic tissue removed from male rats. The effects of T4 or propylthiouracil administration in vivo on hypothalamic iNT content and release was examined as well. T3 (10(-7) M) stimulated iNT release in vitro [45.3 +/- (SE) 1.8 vs. 32.0 +/- 1.9 pg/hypothalamus 30 min-1, P less than 0.005] and a dose-dependent response was observed from 10(-9) M to 10(-7) M; rT3, TRH, and TSH were without effect. T4 administration in vivo caused a reduction in hypothalamic iNT content (5.77 +/- 0.24 vs. 6.57 +/- 0.37 ng/mg protein, P less than 0.05) whereas the induction of hypothyroidism with propylthiouracil and 131I resulted in an increase in iNT content (8.25 +/- 0.27 ng/mg protein, P less than 0.001). Basal release of hypothalamic iNT was similar in all three groups but 58 mM KCl-induced release from hypothyroid hypothalami was impaired. These results indicate a positive influence of T3 on hypothalamic iNT release and have led us to the hypothesis that T3 exerts a negative feedback effect on its own secretion via inhibition of TSH release by NT.