Activation of the G-protein-coupled receptor GPR54 by kisspeptins during normal puberty promotes the central release of gonadotropin-releasing hormone (GnRH) that, in turn, leads to reproductive maturation. In humans and mice, a loss of function mutations of GPR54 prevents the onset of puberty and leads to hypogonadotropic hypogonadism and infertility. Using electrophysiological, morphological,...

Context Kisspeptin (KISS1), a recently discovered neuropeptide that acts upstream of gonadotropin-releasing hormone (GnRH) neurons, is critical for maturation and function of the reproductive axis. This review aimed at providing comprehensive and up-to-date information on Kisspeptin and its role in female reproduction. Evidence Acquisition A literature review was performed using PubMed for al...

Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH). Mutations in three genes--KAL1, GNRHR and FGFR1--account for 15-20% of all causes of IHH/KS. Nearly all mutations are point mutations identified by traditional PCR-based DNA sequencing. The relatively n...

Recent genetic analysis has suggested that the expression of the orphan receptor GPR54 is essential for the onset of puberty in both rodents and humans. Indirect evidence has suggested that this action is via gonadotropin-releasing hormone induction of luteinizing hormone release. The experiments described here were intended to provide direct evidence that metastin, the naturally occurring liga...

In order to find novel modulators of gonadotrophin-releasing hormone (GnRH) secretion, genetic tools were employed in patients with idiopathic hypogonadotrophic hypogonadism (IHH). Mutations in a G-protein coupled receptor, GPR54, were identified, making this receptor a genetic determinant and indisputable gatekeeper of normal reproductive function. This article places these investigations into...

The product of the KiSS-1 gene is absent or expressed at low level in metastatic melanoma and breast cancer compared with their nonmetastatic counterparts. A polypeptide derived from the KiSS-1 product, designated kisspeptin-10 (Kp-10), activates a receptor coupled to Galphaq subunits (GPR54 or KiSS-1R). To study the mechanism by which Kp-10 antagonizes metastatic spread, the effect on CXCR4-me...

Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed i...