Relaxin signaling from natural receptors

The heterodimeric peptide hormone relaxin in most cells appears to signal through a G-protein-coupled receptor, LGR7. Whereas in artificial cell systems, made by transfection of receptor-expressing gene constructs into cells normally not presenting the receptor, classic activation of adenylate cyclase appears to be mediated by Gs, in cells naturally expressing the receptor, this type of coupling appears to be very weak. Instead, there is good evidence of other intermediate steps involving cytoplasmic components and tyrosine kinase activity. Part of the complexity of relaxin signaling is also manifest in the variable time course of cAMP production evident in the THP-1 cell line, which appears to depend on passage number and, hence, presumably on differentiation status. It is therefore important to distinguish between immediate early effects, short to mid-term responses, and long-term responses likely the consequences of specific gene upregulation.