RELAXIN BINDS TO AND ELICITS A RESPONSE FROM CELLS OF THE HUMAN MONOCYTIC CELL-LINE, THP-1

Relaxin is a 6-kDa peptide of the insulin family that is present at in creased levels in the circulation during pregnancy. Its functions at t hat time are thought to include maintenance of myometrial quiescence, regulation of plasma volume, and release of neuropeptides, such as oxy tocin and vasopressin. The protein also promotes connective tissue rem odeling, which allows cervical ripening and separation of the pelvic s ymphysis in various mammalian species. In this report, we provide evid ence for a novel target of relaxin, the human monocytic cell line, THP -1. Relaxin bound with high affinity (K-d = 102 pM) to a specific rece ptor on THP-1 cells. Receptor density was low (similar to 275 receptor s/cell), but binding of relaxin triggered intracelluar signaling event s. Receptor density was not modulated by pretreatment with estrogen, p rogesterone, or a number of other agents known to induce differentiati on of THP-I cells. Cross-linking studies showed radiolabeled relaxin b ound primarily to cell surface proteins with an apparent molecular mas s of >200 kDa. Other members of the insulin-like family of proteins (i nsulin, insulin-like growth factors I and II, and relaxin-like factor) were unable to displace the binding of relaxin to THP-1 cells, sugges ting that a distinct receptor for relaxin exists on this monocyte/macr ophage cell line.