Adrenomedullin: A Novel Peptide Requires Coordination Of Genetic, Physiologic And Environmental Factors

A healthy pregnancy requires strict coordination of genetic, physiologic, and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Adrenomedullin (ADM) is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide (CGRP) initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla, endothelial and vascular smooth muscle cells, myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor (CRLR), a member of serpentine receptor superfamily, and receptor activity modifying protein (RAMP) type 2 or 3. ADM has also some affinity for CGRP receptor composed of CRLR and RAMP1. Supported by mechanistic studies in genetic animal models, there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With measurement of foetal resorption sites, we can examine the importance of adrenomedullin, a peptide hormone in pregnancy which alters due to genetic, physiologic and environmental factors. A growing body of evidence illustrates AM as a pivotal component in normal physiology and disease with marked beneficial effects in the host defense mechanism.

REFERENCES

[1] Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. 1993. Eto T.Biochem Biophys Res Commun. 2012 Aug 31; 425 (3):548-55. Do I: 10.1016/j.bbrc.2012.08.022.

[2] Patricia M. Lenharta and Kathleen M. Carona,* Adrenomedullin and Pregnancy: Perspectives from Animal Models to Humans.Trends Endocrinol Metab. 2012 October; 23(10): 524�532. doi:10.1016/j.tem.2012.02.007. .

[3] K.R.Padma, Dr.P.Josthna, K.R.Don. Adrenomedullin receptors and functions of this novel peptide in implantation.Vol: I Issue: I Aug.-2013, ISSN 2347-2723

[4] Johji Kato, Toshihiro Tsuruda, Toshihiro Kita, Kazuo Kitamura, Tanenao Eto Adrenomedullin A Protective Factor for Blood Vessels (Arterioscler Thromb Vasc Biol. 2005; 25:2480-2487.)

[5] McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, and Foord SM. 1998. RAMPs regulate the transport and ligand binding specificity of the calcitonin-receptor-like receptor. Nature 393:333-339. doi: 10.1038/30666

[6] Penchalaneni J, Wimalawansa SJ, Yallampalli C: Adrenomedullin antagonist treatment during early gestation in rats causes fetoplacental growth restriction through apoptosis. Biol Reprod 2004, 71:1475-1483.

[7] Hayakawa H, Hirata Y, Kakoki M, Suzuki Y, Nishimatsu H, Nagata D, Suzuki E, Kikuchi K, Nagano T, Kangawa K, Matsuo H, Sugimoto T, Omata M. Role of nitric oxide-cGMP pathway in adrenomedullin induced vasodilation in the rat. Hypertension. 1999; 33:689�693.

[8] Ishiyama Y, Kitamura K, Ichiki Y, Nakamura S, Kida O, Kangawa K, Eto T. Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol. 1993;241:271�273.

[9] Kano H,Kohno M, Yasunari K, Yokokawa K,Horio T,Ikeda M, Minami M,Hanehira T, Takeda T, Yoshikawa J (1996) Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells. J. Hypertens 14:209-213. 10.

[10] Kawai J, Ando K, Tojo A, Shimosawa T, Takahashi K, Onozato ML, Yamasaki M, Ogita T, Nakaoka T, and Fujita T. 2004. Endogenous adrenomedullin protects against vascular response to injury in mice. Circulation109:11471153.doi:10.1161/01.CIR.0000117231.40057.6D

[11] Marshall, J. C. (2005) Neutrophils in the pathogenesis of sepsis. Crit.Care Med. 33, S502�S505.

[12] Ogoshi M, et al. Evolutionary history of the calcitonin gene-related peptide family in vertebrates revealed by comparative genomic analyses. Peptides. 2006; 27:3154�3164. [PubMed: 17092606]

[13] Minegishi T, et al. Adrenomedullin and atrial natriuretic peptide concentrations in normal pregnancy and pre-eclampsia. Mol Hum Reprod. 1999; 5:767�770. [PubMed: 10421805]

[14] Zhao Y, et al. PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium. Oncogene. 1998;16:409�415. (PubMed: 9467966)

[15] Lee KY, DeMayo FJ. Animal models of implantation. Reproduction. 2004; 128:679�695.[PubMed: 15579585]

[16] Li L, et al. Adrenomedullin in rat follicles and corpora lutea: expression, functions and interaction with endothelin-1. Reprod Biol Endocrinol. 2011; 9:111. [PubMed: 21824440]

[17] Kraus DM, Feng L, Heine RP, Brown HL, Caron KM, Murtha AP et al.Cigarette smoke-induced placental adrenomedullin expression and trophoblast cell invasion. Reprod Sci 2014; 21: 63�71.

[18] Li J, Ren Y, Dong X, Zhong G, Wu S, Tang C: Roles of different peptide fragments derived from proadrenomedullin in the regulation of vascular tone in isolated rat aorta. Peptides, 2003, 24, 563�568.