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Synonyms:GNRH, GNRH I, GNRH1, Gnrh2, GNRHA, GONADORELIN, GONADOTROPIN, Gonadotropin releasing hormone, GRH, hpg, LHRH, Lhrh1, LNRH, Rgnrhg1

GnRH Signaling in Pituitary Cells

Gonadotrophin-releasing hormone (GnRH) is a hypothalamus-derived decapeptide component of the hypothalamus-pituitary-gonadal axis that regulates the biosynthesis and secretion of the gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by pituitary gonadotrope cells through high-affinity GnRH receptor (GnRHR). Gn-releasing factor is released from the hypothalamus in an estrous cycle-linked pulsatile pattern. LH and FSH are heterodimers that share an alpha subunit, but have unique beta subunits. The secretion and expression level of the β-subunits of LH and FSH αβ-heterodimers are regulated differentially throughout the menstrual cycle by the frequency and amplitude of GnRH pulses from the hypothalamus. This differential signaling for LH versus FSH synthesis and secretion is linked to the density of surface expressed GnRH-receptors. High levels of GnRH-receptor density correlate with increase levels of LH beta subunit mRNA and lower levels with increase FSH beta subunit mRNA.

Gn-releasing factor receptors are G-protein coupled receptors (GPCR) that are coupled to the pertussis toxin-insensitive G-protein alpha q/11 (Gαq/11)) family which link to inositol phospholipid turnover via phospholipase Cbeta (PLCbeta). PLCbeta cleavage of PIP2 promotes the mobilization of calcium and the activation of protein kinase C isoforms followed by sequential activation of phospholipase D and phospholipase A2. PKC activation leads to activation of the MAP-kinases, ERK, JNK and p38. The elevation of cAMP and activation of PKA via GnRH-receptor activation is G-protein subunit-independent and believed to result from activation of a calcium/calmodulin activated adenylyl cyclase downstream from G-protein activation.