Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, 5 Fu-Shin Street, Kweishan, Taoyuan 333, Taiwan.
Curr Protein Pept Sci. 2013 Aug;14(5):393-406. doi: 10.2174/13892037113149990056.
Adrenomedullin (ADM), calcitonin gene-related peptides (α- and β-CGRPs), and intermedin/adrenomedullin 2 (IMD/ADM2) are major regulators of vascular tone and cardiovascular development in vertebrates. Recent research into their functions in reproduction has illuminated the role of these peptides and their cognate receptors (calcitonin receptor-like receptor/receptor activity-modifying protein (CLR/RAMP) receptors) in fetal-maternal blood circulation, fetoplacental development, female gamete development, and gamete movement in the oviduct. Although ADM family peptides function in a temporally and spatially specific manner in various reproductive processes, they appear to act via a similar set of second messengers, including nitric oxide, cyclic GMP, cyclic AMP, and calcium-activated potassium channels in different tissues. These discoveries supported the view that CLR/RAMP receptors were recruited to perform a variety of newly evolved reproductive functions during the evolution of internal reproduction in mammals. These advances also provided insight into how CLR/RAMP receptor signaling pathways coordinate with other physiological adaptions to accommodate the extra metabolic needs during pregnancy, and captured some important details as to how fetal-maternal vascular communications are generated in the first place. Furthermore, these findings have revealed novel, promising opportunities for the prevention and treatment of aberrant pregnancies such as pregnancy-induced hypertension, preeclampsia, and tubal ectopic pregnancy. However, significant efforts are still needed to clarify the relationships between certain components of the CLR/RAMP signaling pathway and aberrant pregnancies before CLR/RAMP receptors can become targets for clinical management. With this understanding, this review summarizes recent progresses with particular focus on clinical implications.
肾上腺髓质素 (ADM)、降钙素基因相关肽 (α-和 β-CGRP) 和中介素/肾上腺髓质素 2 (IMD/ADM2) 是脊椎动物血管张力和心血管发育的主要调节剂。最近对它们在生殖中的功能的研究阐明了这些肽及其同源受体 (降钙素受体样受体/受体活性修饰蛋白 (CLR/RAMP) 受体) 在胎儿-母体血液循环、胎-胎盘发育、女性配子发生和输卵管中配子运动中的作用。尽管 ADM 家族肽在各种生殖过程中以时间和空间特异性的方式发挥作用，但它们似乎通过类似的第二信使发挥作用，包括不同组织中的一氧化氮、环鸟苷酸、环腺苷酸和钙激活的钾通道。这些发现支持了这样一种观点，即 CLR/RAMP 受体在哺乳动物内部生殖进化过程中被招募来执行各种新进化的生殖功能。这些进展还深入了解了 CLR/RAMP 受体信号通路如何与其他生理适应协调，以适应怀孕期间额外的代谢需求，并首先了解了胎儿-母体血管通讯是如何产生的。此外，这些发现为预防和治疗异常妊娠（如妊娠高血压、子痫前期和输卵管异位妊娠）提供了新的、有希望的机会。然而，在 CLR/RAMP 受体成为临床管理的目标之前，仍需要做出巨大努力来阐明 CLR/RAMP 信号通路的某些成分与异常妊娠之间的关系。有了这种理解，本综述总结了最近的进展，特别关注临床意义。
