Glycoprotein Hormone GPCR Assays
Background of Glycoprotein Hormone Receptors
Glycoprotein hormone receptors (GpHRs) are a family of G protein-coupled receptors referred to as follitropin receptor (FSH receptor), lutropin receptor (LH receptor), and thyrotropin receptor (TSH receptor). GpHRs are possibly present at the cell surface as di/oligomers. Few pharmacological studies on GpHRs have been conducted so far. The murine monoclonal antibodies as an antagonist acting on TSH have been established. The development of agonists and antagonists of GpHRs could offer us a chance for the optimization of gonadal function and thyroid gland function.
Fig.1 Schematic diagram of the proposed two-step receptor activation mechanism of FSHR monomer. (Jiang, 2014)
Distributions and Functions of Glycoprotein Hormone Receptors
The FSH and LH receptors act as important regulators of gonadal function. The FSH receptors are found in the testis, placenta, decidua, bone, and endothelium, responsible for spermatogenesis and folliculogenesis. The LH receptors are expressed in placental chorionic villous macrophages, ovary, fallopian tubes, endometrium, kidney, and skin, playing a role in steroidogenesis and ovulation. The TSH receptors are distributed throughout the thyroid gland and in the brain, mainly stimulating thyroid hormone production, thyroid development, and thyroid cell differentiation.
Subtypes and Mechanisms of Glycoprotein Hormone Receptors
The family of GpHRs contains three subtypes of G protein-coupled receptors, including the FSH receptor, LH receptor, and TSH receptor. They promote signal transduction primarily through Gs proteins to stimulate adenylyl cyclase, and secondary transduction stimulates phospholipase C through coupling Gq/G11 protein.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| FSH receptor | FSHR |
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| LH receptor | LHCGR |
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| TSH receptor | TSHR |
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Assay List of Glycoprotein Hormone Receptors
Creative Biolabs can provide a range of assays of glycoprotein hormone receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | The intramolecular agonist is obligate for activation of glycoprotein hormone receptors |
| Journal | The FASEB Journal |
| Published | 2020 |
| Abstract | Unlike most hormone-like G protein-coupled receptors, the glycoprotein hormone receptors have a large extracellular N-terminus for hormone binding. The hormones mediate their action via Tethered Agonistic Ligand (TALI) instead of activating the transmembrane domain. The intramolecular agonist was initially indicated by site-directed mutation studies and activating peptides derived from the extracellular hinge region. The study combined systematic mutagenesis studies at the luteinizing hormone receptor (LH receptor) and the thyroid-stimulating hormone receptor (TSHR) with a drug-like agonist (E2) of the TSHR. They also used structural homology modeling to study the functional and structural properties defining the TALI region. |
| Result |
The study reported that TALI is predisposed to constitutively activate GPHR. The experimental result showed that GPHR contained a tethered agonistic ligand TALI that undergoes structural changes upon GPH binding. It was indicated that the TALI was able to rearrange GPHR into a fully active conformation. In addition, the TALI region stabilized active GPHR conformation and is not involved in the activation of the TSHR by E2. TALI established particular interactions between the transmembrane domain and N-terminus in the conformation of the active state. The study showed that stabilization of an active state was dependent on TALI, including activation by hormones and constitutively activating mutations. Besides, the study has indicated that the small molecule agonist E2 was able to directly bind to the 7TMD and did not require TALI for its agonistic action.
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Fig.2 The G1.31P mutant activates the N terminal truncated TSHR with the p10 region, but not in the corresponding LHR variant. (Schulze, 2020)
References
- Jiang, X.; et al. Structural biology of glycoprotein hormones and their receptors: insights to signaling. Molecular and cellular endocrinology. 2014 382(1): 424-451.
- Schulze, A.; et al. The intramolecular agonist is obligate for activation of glycoprotein hormone receptors. The FASEB Journal. 2020, 34(8): 11243-11256.
