GNRHR - Gonadotropin Releasing Hormone Receptor | Elisa - Clia - Antibody - Protein

Background:

GNRHR is a G protein-coupled receptor primarily expressed in the anterior pituitary gland and the hypothalamus. GNRHR mediates the biological effects of gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH), which is secreted by the hypothalamus. GnRH, a decapeptide hormone, binds to and activates GNRHR. GNRHR plays a crucial role in regulating reproductive function and gonadotropin secretion by mediating the effects of GnRH. Dysregulation of GNRHR signaling can lead to reproductive disorders with significant clinical implications, highlighting its importance as a therapeutic target in reproductive medicine.

Structure:

Extracellular N-Terminus:

The N-terminal domain of GnRHR is relatively short compared to other GPCRs. It plays a role in ligand (GnRH) binding.

Transmembrane Domain (TMD):

• The TMD of GnRHR consists of seven alpha-helices (TM1 to TM7) that span the cell membrane. These helices are typical of GPCR structures and form a helical bundle that is essential for receptor function.
• Helices Arrangement: The helices are arranged in a characteristic 7-helix bundle, creating a binding pocket for the ligand within the plane of the cell membrane.
• Binding Pocket: The binding pocket is formed by the extracellular parts of the helices, particularly TM3, TM5, TM6, and TM7, which interact with GnRH.

Intracellular Loops:

• The intracellular loops (IL1, IL2, IL3) connect the transmembrane helices and play critical roles in G protein coupling and signal transduction.
• The third intracellular loop (IL3) and the C-terminal tail are particularly important for interacting with G proteins and other signaling molecules.

Extracellular Loops:

• The extracellular loops (EL1, EL2, EL3) connect the transmembrane helices on the extracellular side and contribute to ligand binding and receptor stability.
• EL2, in particular, is involved in forming the ligand-binding site and maintaining receptor conformation.

Intracellular C-Terminus:

• Unlike many GPCRs, the C-terminal tail of GnRHR is short and lacks significant regulatory sequences such as phosphorylation sites, which are common in other GPCRs for receptor desensitization and internalization.

Physiological Functions:

• Regulation of Reproduction: GNRHR activation stimulates the synthesis and secretion of gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from the anterior pituitary gland.
• Gonadal Function: LH and FSH released in response to GnRH regulate gonadal function and steroid hormone production in the ovaries and testes.
• Regulation: GNRHR activity is tightly regulated by factors such as sex steroids (estrogen, testosterone), inhibin, and feedback from gonadal hormones.

Interaction with Other Proteins:

• G Proteins: GnRHR primarily interacts with Gq/11 proteins to initiate the phospholipase C signaling pathway.
• Regulatory Proteins: Although the C-terminal tail of GnRHR is short, it can interact with other regulatory proteins that modulate receptor function, trafficking, and desensitization.

Clinical Implications:

• Mutations or dysregulation of GNRHR can lead to reproductive disorders such as hypogonadotropic hypogonadism, delayed or absent puberty, and infertility.
• GNRHR mutations are associated with idiopathic hypogonadotropic hypogonadism (IHH), a condition characterized by absent or incomplete puberty and infertility due to insufficient gonadotropin secretion.

Therapeutic Potential:

• Drugs targeting GNRHR, such as GnRH agonists and antagonists, are used clinically for the management of conditions such as precocious puberty, endometriosis, and infertility.
• GnRH agonists are used to suppress gonadotropin secretion and sex steroid production in the treatment of hormone-sensitive conditions such as prostate cancer, breast cancer, and endometriosis.