“…Recently, another human insulin/relaxin-like molecule and its nearly identical orthologs in the mouse, rat, 1 Abbreviations: RLN1, gene encoding H1 relaxin; RLN2, gene encoding H2 relaxin; H1 relaxin, human gene 1 relaxin; H2 relaxin, human gene 2 relaxin; H3 relaxin, human gene 3 relaxin; (species) relaxin-3, peptide corresponding to human gene 3 (H3) relaxin in other species; Ley-I-L, Leydig insulin-like peptide; INSL3, gene encoding insulin-like peptide 3; INSL4, gene encoding insulin-like peptide 4; INSL5, gene encoding insulin-like peptide 5; INSL6, gene encoding insulin-like peptide 6; RLF, relaxin-like factor; INSL3, insulin-like peptide 3; INSL4, insulin-like peptide 4; INSL5, insulinlike peptide 5; INSL6, insulin-like peptide 6; LGR, leucine-rich repeat-containing guanine nucleotide binding (G-protein)-coupled receptors; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thryroid-stimulating hormone; Great, G-protein coupled receptor affecting testis descent; LGR7, leucine-rich repeatcontaining guanine nucleotide binding (G-protein)-coupled receptor 7; LGR8, leucine-rich repeat-containing guanine nucleotide binding (G-protein)-coupled receptor 8; GPCR, G-protein coupled receptor; GPCR135, G-protein coupled receptor 135 (orphan receptor nomenclature); GPCR142, G-protein coupled receptor 142 (orphan receptor nomenclature); RXFP1, relaxin family peptide receptor 1; RXFP2, relaxin family peptide receptor 2; RXFP3, relaxin family peptide receptor 3; RXFP4, relaxin family peptide receptor 4; RT-PCR, reverse transcription-polymerase chain reaction; PKA, protein kinase A; SFO, subfornical organ; OVLT, organum vasculosum of the lamina terminalis; ET 1-32 , first 32 amino acids of endothelin peptide; NO, nitric oxide; NOS, nitric-oxide synthase; THP-1, human monocytic cell line; LRR, leucine-rich repeat; LDLa, low-density lipoprotein class A; TM, transmembrane; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; PDE, phosphodiesterase; HEK293, human embryonic kidney (cells); LY294002, 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride; PI3-K, phosphatidyinositol 3 kinase; Erk1/2, extracellular signalling regulated kinase; GR, glucocorticoid receptor; RU486, 17-hydroxy-11-[4-dimethylamino phenyl]-17␣-[1-propynyl]estra-4,9-dien-3-one. 8 and pig were discovered (Bathgate et al, 2002a;Burazin et al, 2002;Kizawa et al, 2003). Because this peptide has the amino acid motif Arg-X-X-X-Arg-X-X-Ile required for relaxin bioactivity in the middle of the B chain and it activates the relaxin receptor (Sudo et al, 2003), it was designated relaxin-3 or in the case of the human relaxin-3 peptide, H3 relaxin ( Fig.…”