Effect of Chronic Treatment with Thyrotropin-Releasing Hormone (TRH) or an Analog of TRH (Linear β-Alanine TRH) on the Hypothalamic-Pituitary-Thyroid Axis

Abstract

The effects of treatment for 5 or 9 days with varying doses of thyrotropin-releasing hormone (TRH) or the linear β-alanine TRH congener (pGlu-His-Pro- β-Ala-NH₂) on serum levels of TSH, T₃ and T₄ were studied in mice and rats. At low doses in rats treatment with TRH for 9 days significantly increased serum levels of T₃ but not serum T₄ whereas a higher dose of TRH (10 mg/kg) reduced serum T₃ levels. β-ALA TRH (0.1–10 mg/kg IP) treatment for 9 days in rats significantly reduced serum T₄ levels whereas serum T₃ levels were only depressed at higher doses (1–10 mg/kg IP) of the peptide. In mice treatment for 5 days with TRH (1 and 10 mg/kg IP) significantly reduced serum levels of T₃ and T₄. In addition, TRH (0.1–10 mg/kg IP) or β-ALA·TRH treatment (1.0–10 mg/kg IP) for 9 days significantly reduced serum TSH levels in rats. TRH (10 mg/kg IP for 9 days) also significantly reduced serum GH levels in rats. No alteration in hypothalamic content of TRH or LHRH was observed after chronic TRH treatment. Some, but not all, of our findings support the hypothesis that treatment with high doses of TRH reduce pituitary-thyroid axis functions by a direct effect on hypophysial TRH receptors.