TRH

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

Signaling Pathways >> Others >> Thyroid Hormone Receptor

Research Areas >> Inflammation/Immunology

Peptides

Research Areas >> Endocrinology

Thyroid hormone receptor

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].

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°C through the experiments including the breeding period. For a statistical analysis, Student's t test (two-tailed) is adopted.

[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.

liothyronine | MGL-3196 | Sobetirome | L-thyroxine | Tiratricol | eprotirome | Protirelin Acetate | TR antagonist 1 | KAT681 | PCO371

MOLECULAR FORMULA :

C16-H22-N6-O4

MOLECULAR WEIGHT :

362.44

WISWESSER LINE NOTATION :

T5NTJ BVZ AVYMV- ET5MVTJ&1- BT5NJ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

5714 ng/kg/1M-C

TOXIC EFFECTS :

Behavioral - coma Cardiac - pulse rate Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 143,264,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

5333 ng/kg/2M-C

TOXIC EFFECTS :

Behavioral - coma Vascular - BP lowering not characterized in autonomic section

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 287,532,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

8 ug/kg/2M-C

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Cardiac - pulse rate increase, without fall in BP

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 287,532,1983

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,727,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>10 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,727,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

514 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,727,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>10 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,727,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>20 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,727,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

921 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,727,1982 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - stillbirth

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,807,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

20 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,807,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

200 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - sex ratio

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,807,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

150 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,807,1974