GNRHR

GNRHR stands for gonadotropin-releasing hormone receptor, a G protein-coupled receptor expressed on pituitary gonadotroph cells. It binds GnRH, triggering secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and stimulating gonadal steroidogenesis.

It signals via Gq/11 leading to phospholipase C beta activation, IP3 and DAG production, intracellular calcium rise, and protein kinase C activation; the pulsatile nature of GnRH dynamically regulates transcription of gonadotropin subunit genes, thereby shaping LH versus FSH output.

Genetic and clinical aspects: The GNRHR gene encodes the receptor. Mutations can cause normosmic congenital hypogonadotropic hypogonadism (nCHH) or isolated hypogonadism due to impaired receptor function or trafficking. Affected individuals typically present with delayed or absent puberty, low gonadotropin and sex steroid levels, and variable reproductive function. Some mutations affect receptor folding and trafficking, reducing cell surface expression.

Diagnosis and treatment: Genetic testing of GNRHR is used in the evaluation of CHH. Management includes hormone replacement to induce puberty and maintain secondary sexual characteristics; in some cases, pulsatile GnRH therapy or gonadotropin-based regimens are used to promote fertility.

Structure and evolution: GNRHR is a member of the rhodopsin-like GPCR family with seven transmembrane domains. It is the primary functional GnRH receptor in humans; in some species, additional GnRH receptor genes exist, reflecting lineage-specific receptor repertoires.