Diverse signalling mechanisms used by relaxin in natural cells and tissues: the evolution of a "neohormone"

Abstract

The small peptide hormone relaxin is a member of a rapidly evolving family of hormones and growth factors, whose mode of action appears to be particularly adapted to purely mammalian physiology. It is representative of a new category of hormones, referred to as neohormones, which appear to have evolved specifically to accommodate the needs of viviparity, lactation and wound repair. The mechanism of receptor signalling has also evolved in this family, with older members using receptor tyrosine kinases and new members such as relaxin adopting 7-transmembrane G-protein coupled receptors. Although relaxin primarily generates cAMP as second messenger, studies of relaxin signalling show that this does not conform to a classic G-protein dependent activation of adenylate cyclase: it requires additional cytoplasmic components, it can involve further coupling to PI3-kinase and PKCzeta and it is absolutely dependent on a tyrosine kinase activity linked closely to the relaxin receptor. Relaxin may also independently activate glucocorticoid receptors. This diversity of signalling leads to a broad range of possible downstream transcriptional effects. Finally, in tissues where relaxin is known to be effective, there is often also local relaxin induction, amplifying the effects of the endocrine hormone.