Last update 01 Nov 2024

TRH x TSHR x TRHR

Last update 01 Nov 2024

Basic Info

Related Targets

TRHTSHRTRHR

Drugs associated with TRH x TSHR x TRHR

Posatirelin

Target

TRH x TRHR x TSHR

Mechanism

TRH agonists [+2]

Active Org.

Chemical Works of Gedeon Richter Plc

Originator Org.

Gedeon Richter USA, Inc.

Active Indication

Nervous System Diseases

Inactive Indication

Cognition Disorders [+1]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRH x TSHR x TRHR

100 Translational Medicine associated with TRH x TSHR x TRHR

0 Patents (Medical) associated with TRH x TSHR x TRHR

Literatures (Medical) associated with TRH x TSHR x TRHR

01 Jan 2022·Endocrine JournalQ4 · MEDICINE

Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Q4 · MEDICINE

Article

Author: Zhang, Yuezhu ; Chen, Huaiji ; Xu, Feng ; Jia, Yiyang ; Sun, Di ; Zhou, Liting ; Xu, Jin ; Wang, Shuyue ; Ye, Lin ; Zhu, Jian ; Wang, Qi ; Liu, Te

Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which results in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms underlying DEHP disrupting the function of the HPTA. DEHP was administered to Wistar rats by gavage at 0, 5, 50, and 500 mg/kg/day for consecutive 28 days and then the rats were sacrificed within 24 h following the last dose. The hormone levels of HPTA were quantified with radioimmunoassay and enzyme-linked immunosorbent assay, the protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, and the expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. The low dose of DEHP increased the body weights of rats. Serum levels of T3, T4, FT3 and FT4 as well as protein and mRNA levels of TSHR decreased in rats treated with 50 mg/kg or 500 mg/kg DEHP compared with those of controls. Although the protein levels of TRH in the hypothalamus or protein and mRNA levels of TRHR in pituitary were up-regulated, serum levels of TSH did not change statistically in rats treated with DEHP. Therefore, DEHP can produce thyroid toxicity and may interfere with the secretion of pituitary TSH. In conclusion, DEHP could interfere with the balance of HPTA of adolescent rats, and disturb the homeostasis of thyroid related hormones and the expression levels of receptors.

01 Jan 2018·Endocrine JournalQ4 · MEDICINE

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Q4 · MEDICINE

Article

Author: Zhang, Yuezhu ; Chen, Huaiji ; Xu, Feng ; Jia, Yiyang ; Sun, Di ; Zhou, Liting ; Xu, Jin ; Ye, Lin ; Wang, Shuyue ; Zhu, Jian ; Wang, Qi ; Liu, Te

Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which has resulted in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms in which DEHP disrupts the function of the HPTA. Wistar rats were administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/day for 28 days and then sacrificed within 24 h following the last dose. Hormones of HPTA was quantified with radioimmunoassay and enzyme-linked immunosorbent assay, protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. Rats treated with DEHP resulted in increased bodyweight, on the HPTA, down-regulated the protein levels of TRH in the hypothalamus, up-regulated the protein and mRNA levels of TRHR in the pituitary, down-regulated mRNA expression of TSHR in the thyroid, while the difference of TSH in various dose groups was not statistically significant and T3, T4, FT3, FT4 levels in serum were decreased compared with control. DEHP could interfere with the balance of HPTA of adolescent rats, and increase the body weight, down-regulate the homeostasis of thyroid related hormones and receptors expression levels.

13 Jun 2016·Comprehensive PhysiologyQ1 · MEDICINE

Hypothalamus-Pituitary-Thyroid Axis.

Q1 · MEDICINE

Review

Author: Wondisford, Fredic E ; Pazos-Moura, Carmen C ; Ortiga-Carvalho, Tania M ; Chiamolera, Maria I

The hypothalamus-pituitary-thyroid (HPT) axis determines the set point of thyroid hormone (TH) production. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the synthesis and secretion of pituitary thyrotropin (thyroid-stimulating hormone, TSH), which acts at the thyroid to stimulate all steps of TH biosynthesis and secretion. The THs thyroxine (T4) and triiodothyronine (T3) control the secretion of TRH and TSH by negative feedback to maintain physiological levels of the main hormones of the HPT axis. Reduction of circulating TH levels due to primary thyroid failure results in increased TRH and TSH production, whereas the opposite occurs when circulating THs are in excess. Other neural, humoral, and local factors modulate the HPT axis and, in specific situations, determine alterations in the physiological function of the axis. The roles of THs are vital to nervous system development, linear growth, energetic metabolism, and thermogenesis. THs also regulate the hepatic metabolism of nutrients, fluid balance and the cardiovascular system. In cells, TH actions are mediated mainly by nuclear TH receptors (210), which modify gene expression. T3 is the preferred ligand of THR, whereas T4, the serum concentration of which is 100-fold higher than that of T3, undergoes extra-thyroidal conversion to T3. This conversion is catalyzed by 5'-deiodinases (D1 and D2), which are TH-activating enzymes. T4 can also be inactivated by conversion to reverse T3, which has very low affinity for THR, by 5-deiodinase (D3). The regulation of deiodinases, particularly D2, and TH transporters at the cell membrane control T3 availability, which is fundamental for TH action. © 2016 American Physiological Society. Compr Physiol 6:1387-1428, 2016.

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