Animal experiment:

Rats[2]Ninety male Wistar rats weighing 200-250 g are subjected to the study. In the first experiment, 50 rats are divided into five groups randomly. Four doses of Protirelin dissolved in physiological saline, i. e., 1 mg/kg, 5mg/kg, 10 mg/kg and 20 mg/kg, are administered intraperitoneally to the four groups and saline to the remaining control group. Rectal temperature is measured at the place 5 cm inner from the anus with the electronic thermister before and after treatment with Protirelin or saline. In the second experiment, 40 rats are thyroidectomized or sham-operated under the anesthesia by thiopental sodium. Ten days after the operation, 20 mg/kg of Protirelin or saline is administered to the thyroidectomized and sham-operated animals by i. p. and rectal temperature is measured using the same method as used in the first experiment. These two experiments are undertaken from 1 p, m, to 4 p. m. and the room temperature is kept at 24±1℃ through the experiments including the breeding period. For a statistical analysis, Student's t test (two-tailed) is adopted.

Protirelin is a highly conserved neuropeptide that exerts the hormonal control of thyroid-stimulating hormone (TSH) levels as well as neuromodulatory functions.

Protirelin (TRH) is an evolutionarily ancient neuropeptide, having its origin before the divergence of protostomes and deuterostomes, and may ancestrally have been involved in the control of postembryonic growth and reproduction[1]. The effect of the thyrotropin-releasing hormone (Protirelin, TRH), one of the hypothalamic releasing hormones, on body temperature is investigated in the rat. Protirelin, in doses of 1, 5, 10 and 20 mg/kg, is injected intraperitoneally to male Wistar rats weighing 200-250 g. Protirelin causes a temporary rise in body temperature dose-dependently. The thyroidectomized rats injected 20 mg/kg of Protirelin which induces a significant hyperthermia in the sham-operated animals, fail to show a rise in body temperature. The present results suggest that a release of thyroid hormone might participate in the hyperthermic action of Protirelin[2].

[1]. Van Sinay E, et al. Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4065-E4074. [2]. Noda Y, et al. Hyperthermia induced by thyrotropin-releasing hormone (TRH, Protirelin) in the rat. Kurume Med J. 1979;26(2):107-12.