Effect of Chronic Treatment with Thyrotropin-Releasing Hormone (TRH) or an Analog of TRH (Linear <i>β</i>-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.

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

“…The animals did not show any significant weight loss. The small increase in temperature observed during the first 2 days of treatment is difficult to be attributed to the thyroid hormones, since TRH was shown to influence directly the body temperature in rats [16], The following TSH decrease during the rest of our study is in agreement with the results of other au thors who have also reported a decreased TSH release in vitro [17] and in vivo [18] in rats and in man after repeated or chronic treatment with TRH [19][20][21], Most of these authors have used several doses of TRH ad ministered intravenously or orally at various time schedules. We used oral TRH in drink ing water, which is water soluble and stable and in addition has a longer biological halflife than the intravenous form.…”

Pulsatile TSH Secretion during 48-Hour Continuous TRH Infusions

“…However, it is not known whether TSH pulses depend on pulsatile thyrotropin-releasing hormone (TRH) secretion, in analogy to hypothalamic control of gonadotropin and growth hormone (GH) pulses (3,4). Con¬ tinuous TRH infusions in humans and animals cause initial increases in TSH levels, which diminish despite continued TRH administration (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). A more recent study has also shown greater TSH release when TRH is given in intermittent, rather than continuous, fashion (19).…”

“…This response, noted in TRH infusion studies (5)(6)(7)(8)10,11,14,16,17), may interfere with the assessment of TSH pulses. This problem can be avoided by studying patients with primary hypothy¬ roidism, who cannot increase thyroid hormone synthesis in response to TRH. We hypothesized that pulsatile TSH secretion depends on pulsatile TRH input from the hypothalamus.…”

Effects of Prenatal Maternal TRH Stimulation on the Postnatal Ability of Neonatal Piglets to Cope with a Cold Challenge

“…The subsequent decline and maintenance of lower levels could be explained by a combination of negative feedback and other regulatory mechanisms which are put in place upon recognizing abnormally high concentrations of these hormones. These mechanisms include downregulation of TRH receptors in the hypophysis [16] and direct reduction in TRH receptor numbers in response to elevated T 3 levels which then result in reduced production of TSH [17]. Further regulation can be also mediated by increased rate of hepatic [18] and peripheral [19] deiodination of thyroid hormones.…”