Activation of the thyrotropin-releasing hormone (TRH) receptor by a direct precursor of TRH, TRH-Gly

Yamada, Masanobu; Iwasaki, Tadaaki; Satoh, Tetsurou; Monden, Tsuyoshi; Konaka, Shuntaro; Murakami, Masami; Iriuchijima, Tokuji; Mori, Masataka

doi:10.1016/0304-3940(95)11861-p

Cited by 17 publications

(2 citation statements)

References 15 publications

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“…Several of these intervening peptides have been reported to possess biological activity: the intervening peptide between the 4th and 5th rat TRH progenitor sequences causes inhibition of the release of ACTH from the pituitary (10). Furthermore, TRH-Gly, a direct precursor of TRH has been identified throughout the body and has been reported to bind and stimulate TRH receptor subtype 1 (12). Furthermore, TRH-Gly, a direct precursor of TRH has been identified throughout the body and has been reported to bind and stimulate TRH receptor subtype 1 (12).…”

Section: Structure and Expression Of Trh And Its Gene In The Brainmentioning

confidence: 99%

Thyrotropin-releasing hormone (TRH) in the cerebellum

2008

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Thyrotropin-releasing hormone (TRH) was originally isolated from the hypothalamus. Besides controlling the secretion of TSH from the anterior pituitary, this tripeptide is widely distributed in the central nervous system and regarded as a neurotransmitter or modulator of neuronal activities in extrahypothalamic regions, including the cerebellum. TRH has an important role in the regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation. TRH controls energy homeostasis mainly through its hypophysiotropic actions to regulate circulating thyroid hormone levels. Recent investigations have revealed that TRH production is regulated directly at the transcriptional level by leptin, one of the adipocytokines that plays a critical role in feeding and energy expenditure. The improvement of ataxic gait is one of the important pharmacological properties of TRH. In the cerebellum, cyclic GMP has been shown to be involved in the effects of TRH. TRH knockout mice show characteristic phenotypes of tertiary hypothyroidism, but no morphological changes in their cerebellum. Further analysis of TRH-deficient mice revealed that the expression of PFTAIRE protein kinase1 (PFTK1), a cdc2-related kinase, in the cerebellum was induced by TRH through the NO-cGMP pathway. The antiataxic effect of TRH and TRH analogs has been investigated in rolling mouse Nagoya (RMN) or 3-acetylpyridine treated rats, which are regarded as a model of human cerebellar degenerative disease. TRH and TRH analogs are promising clinical therapeutic agents for inducing arousal effects, amelioration of mental depression, and improvement of cerebellar ataxia.

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Section: Structure and Expression Of Trh And Its Gene In The Brainmentioning

confidence: 99%

Thyrotropin-releasing hormone (TRH) in the cerebellum

2008

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“…On the other hand, TRH is biosynthesized from a TRH precursor, TRH-glycine (TRH-Gly) 6, a tetrapeptide which is degraded by a specific enzyme in the brain and displays several biological activities [35][36][37] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of in Vivo Anti-hypothermic Effect of the N- and C-Terminus Modified Thyrotropin-Releasing Hormone Mimetic: [(4S,5S)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-[3-(thiazol-4-yl)-L-alanyl]-L-prolinamide

Kobayashi

Satô

Sugita

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

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We explored orally effective thyrotropin-releasing hormone (TRH) mimetics, which show high central nervous system effects in structure-activity relationship studies based on in vivo antagonistic activity on reserpine-induced hypothermia (anti-hypothermic effect) in mice starting from TRH. This led us to the TRH mimetic: [(4S,5S)-(5-methyl-2-oxooxazolidine-4-yl)carbonyl]-[3-(thiazol-4-yl)-L-alanyl]-L-prolinamide 1, which shows a higher anti-hypothermic effect compared with that of TRH after oral administration. We next attempted further chemical modification of the N-and C-terminus of 1 to find more orally effective TRH mimetics. As a result, we obtained several N-and C-terminus modified TRH mimetics which showed high anti-hypothermic effects.

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Endocrinology1

Vogel

Schölkens

et al. 2002

Drug Discovery and Evaluation

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Activation of the thyrotropin-releasing hormone (TRH) receptor by a direct precursor of TRH, TRH-Gly

Cited by 17 publications

References 15 publications

Thyrotropin-releasing hormone (TRH) in the cerebellum

Thyrotropin-releasing hormone (TRH) in the cerebellum

Synthesis and Evaluation of <i>in Vivo</i> Anti-hypothermic Effect of the N- and C-Terminus Modified Thyrotropin-Releasing Hormone Mimetic: [(4<i>S</i>,5<i>S</i>)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-[3-(thiazol-4-yl)-L-alanyl]-L-prolinamide

Endocrinology1

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