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 PKCς and it is absolutely dependent on a tyrosine kinase activity linked closely to the relaxin receptor. Relaxin may also independendy 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.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
- Glucocorticoid Receptor
- Adenylate Cyclase
- Related Peptide
- Human Endometrial Stromal Cell
- Mammalian Physiology
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Ivell R, Bathgate RAD. Hypothesis: Neohormone systems as exciting targets for drug development. Trends Endocrinol Metab 2006; 17:123.
Bathgate RA, Hsueh AJ, Ivell R et al. International Union of Pharmacology. Recommendations for the nomenclature of receptors for relaxin family peptides. Pharmacol Rev 2006; 58:7–31.
Wilkinson TN, Speed TP, Tregear GW et al. Evolution of the relaxin-like peptide family. BMC Evol Biol 2005; 5:14.
Mazerbourg S, Bouley DM, Sudo S et al. Leucine-rich repeat-containing G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality. Mol Endocrinol 2004; 18:2241–2254.
Halls ML, Bathgate RA, Summers RJ. Comparison of signalling pathways activated by the relaxin family peptide receptors, RXFP1 and RXFP2, revealed using reporter genes. J Pharmacol Exp Ther 2006; (epub ahead of print).
Fei DT, Gross MC, Lofgren JL et al. 1990. Cyclic AMP response to recombinant human relaxin by cultured human endometrial cells-a specific and high throughput in vitro bioassay. Biochem Biophys Res Commun 1990; 170:214–222.
Bartsch O, Bartlick B, Ivell R. Relaxin signalling links tyrosine phosphorylation to phosphodiesterase and adenylyl cyclase activity. Mol Hum Reprod 2001; 7:799–809.
Bartsch O, Bartlick B, Ivell R. Phosphodiesterase 4 inhibition synergizes with relaxin signalling to promote decidualization of human endometrial stromal cells. J Clin Endocrinol Metab 2004; 89:324–334.
Halls ML, Bathgate RA, Summers RJ. Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signalling by distinct mechanisms. Mol Pharmacol 2006; 70:214–226.
Nguyen BT, Yang L, Sanborn BM et al. Phosphoinositide 3-kinase activity is required for biphasic stimulation of cyclic adenosine 3′,5′-monophosphate by relaxin. Mol Endocrinol 2003; 17:1075–1084.
Nguyen BT, Dessauer CW. Relaxin stimulates protein kinase C zeta translocation: requirement for cyclic adenosine 3′,5′-monophosphate production. Mol Endocrinol 2005; 19:1012–1023.
Kalbag SS, Roginsky MS, Jelveh Z et al. Phorbol ester, prolactin and relaxin cause translocation of protein kinase C from cytosol to membranes in human endometrial cells. Biochim Biophys Acta 1991; 1094:85–91.
Bartsch O, Bartlick B, Ivell R. Relaxin signal transduction couples tyrosine phosphorylation to cAMP upregulation. In: Tregear GW, Ivell R, Bathgate RAD, Wade JD, eds. Relaxin 2000: Proceedings of the 3rd International Conference on Relaxin and Related Peptides. Kluwer Academic Publishers; Dordrecht, Netherlands 2001; 309–316.
Mayerhofer A, Engling R, Stecher B et al. Relaxin triggers calcium transients in human granulosa-lutein cells. Eur J Endocrinol 1995; 132:507–513.
Dschietzig T, Bartsch C, Stangl V et al. Identification of the pregnancy hormone relaxin as glucocorticoid receptor agonist. FASEB J 2004; 18:1536–1538.
Dodge KL, Sanborn BM. Evidence for inhibition by protein kinase A of receptor/G alpha(q)/phospholipase C (PLC) coupling by a mechanism not involving PLCbeta2. Endocrinology 1998; 139:2265–2271.
Ivell R, Balvers M, Pohnke Y et al. Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates. Reprod Biol Endocrinol 2003; 1:114.
Downing SJ, Hollingsworth M. Action of relaxin on uterine contraction—a review. J Reprod Fertil 1993; 99:275–282.
Ivell R, Einspanier A. Relaxin peptides are new global players. Trends Endocrinol Metab 2002; 13:343–348.
Anand-Ivell R, Heng K, Ivell R. Relaxin signaling in THP-1 cells uses a novel phospholyrosine-dependent pathway. Mol Cell Endocrinol 2007; (in press).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Ivell, R., Heng, K., Anand-Ivell, R. (2007). Diverse Signalling Mechanisms Used by Relaxin in Natural Cells and Tissues: The Evolution of a “Neohormone”. In: Agoulnik, A.I. (eds) Relaxin and Related Peptides. Advances in Experimental Medicine and Biology, vol 612. Springer, New York, NY. https://doi.org/10.1007/978-0-387-74672-2_3
Download citation
DOI: https://doi.org/10.1007/978-0-387-74672-2_3
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-74670-8
Online ISBN: 978-0-387-74672-2
eBook Packages: MedicineMedicine (R0)