TRH Family Related Drug Discovery Products
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The hypothalamic tripeptide thyrotropin-releasing hormone (TRH) stimulates the anterior pituitary gland's release of thyrotropin by sitting on top of the hypothalamus/pituitary/thyroid axis. Prolactin secretion is stimulated by TRH as well. TRH binding sites were eventually discovered in brain membranes after being initially defined in clonal rat pituitary cell lines. When heterotrimeric G proteins were first discovered, it was believed that they could only transmit signals from receptors connected to adenylyl cyclase. The TRH receptors are a subset of the GPCR family. Humans and most higher mammals have a single gene encoding the TRH receptor, while rodents have two genes encoding analogous receptors, TRHR1 and TRHR2.
Fig.1. Endocrine role of thyrotropin-releasing hormone. (Hinkle, 2012)
Creative Biolabs provides high-quality TRH family drug discovery in vitro assays and related products to meet the needs of our customers:
Overview of TRH Family
TRH receptor ligation, which has been found in the brain, uterus, ovary, and testis, as well as intestinal epithelial cells, retina, lymphoid tissue, and bone marrow, mediates the cellular action of TRH. TRH exerts all of its cellular actions through a single form of TRHR that is unique to humans. Two types, TRHR1 and TRHR2, are expressed by rodents and various other species. Both receptor types are made up of seven-transmembrane receptors that are phosphorylated in response to TRH binding. By hydrolyzing phosphatidylinositol 4,5-biphosphate (PIP) into inositol 1,4,5-triphosphosphate (IP3) and 1,2-diacylglycerol (DAG), phospholipase Cβ is stimulated as a result of activation. Protein kinase C (PKC) is activated and intracellular calcium levels rise. Additionally, calcium/calmodulin-dependent protein kinase and mitogen-activated protein kinase (MAPK) are stimulated by TRHR1 signaling.
Fig.2. Stimulation of prolactin secretion by TRH. (Fröhlich & Wahl, 2019)
TRH Family Drug Discovery
The most significant function of TRH in the human body is the control of thyroid hormone secretion. Differentiating between various types of central hypothyroidism is presently the main diagnostic purpose of the TRH stimulation test. Due to the fact that TRH impacts were more noticeable at high PRL levels, effects on PRL levels may be significant. It is unclear how elevated amounts of TRH, TRH-like peptides, TSH, and PRL relate to breast cancer. Since studies have also found a link between breast cancer and high levels of T3, T4, anti-thyroid antibody, and PRL, an exclusive function for TRH levels in its pathophysiology is improbable. Since thyroid hormone and prolactin have such a wide variety of effects on the body, it is challenging to pinpoint the precise targets of direct TRH activity.
References
- Hinkle, P.M.; et al. Desensitization, trafficking, and resensitization of the pituitary thyrotropin-releasing hormone receptor. Frontiers in neuroscience. 2012, 6: 180.
- Fröhlich, E.; Wahl, R. The forgotten effects of thyrotropin-releasing hormone: Metabolic functions and medical applications. Frontiers in neuroendocrinology. 2019, 52: 29-43.