Luteinizing hormone/choriogonadotropin receptor

Luteinizing hormone up-regulates cholesterol side chain cleaving enzyme in sensitive tissues, the first step of all human steroidogenesis.

The seven transmembrane α-helix structure of a G protein-coupled receptor such as LHCGR

Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) is a transmembrane receptor that is expressed on the surface of ovarian and testicular tissues. It plays a critical role in human reproduction, mediating the effects of luteinizing hormone (LH) and human chorionic gonadotropin (hCG). These hormones are essential for ovulation, steroidogenesis, and the maintenance of the corpus luteum in females, as well as testosterone production and spermatogenesis in males.

Structure

The LHCGR is a member of the G protein-coupled receptor (GPCR) family, which is characterized by seven transmembrane domains. The receptor is activated upon binding of its ligands, LH or hCG, leading to a conformational change that triggers intracellular signaling pathways. These pathways involve the activation of adenylyl cyclase, resulting in an increase in cyclic AMP (cAMP) levels and subsequent activation of protein kinase A (PKA), which then phosphorylates various target proteins to exert its biological effects.

Function

In females, the LHCGR is primarily involved in the regulation of the menstrual cycle and fertility. The binding of LH to the receptor in the ovary stimulates the production of estrogens during the follicular phase and induces ovulation. Post-ovulation, LH supports the formation and maintenance of the corpus luteum, which secretes progesterone to prepare the endometrium for potential pregnancy.

In males, the receptor is found on the Leydig cells of the testes, where LH stimulates the production of testosterone. Testosterone is crucial for the development of male secondary sexual characteristics, spermatogenesis, and libido.

Clinical Significance

Mutations in the gene encoding the LHCGR can lead to reproductive disorders. In females, such mutations may result in ovarian hyperstimulation syndrome (OHSS) or infertility due to anovulation. In males, mutations can lead to testicular failure and hypogonadism, affecting fertility and secondary sexual characteristics.

The LHCGR is also a target for fertility treatments. Assisted reproductive technology (ART) procedures, such as in vitro fertilization (IVF), often involve the administration of hCG to mimic the LH surge and induce ovulation.

Research Directions

Research on the LHCGR continues to explore its role in fertility, its mechanisms of action, and its potential as a target for treating reproductive disorders. Advances in understanding the receptor's structure and function may lead to the development of new therapeutic agents for infertility and other reproductive health issues.

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