Power Michael L, Schulkin Jay
Department of Research, American College of Obstetricians and Gynecologists, Washington, DC 20024, USA.
Am J Hum Biol. 2006 Jul-Aug;18(4):431-47. doi: 10.1002/ajhb.20521.
Corticotropin-releasing hormone (CRH) is an ancient regulatory molecule. The CRH hormone family has at least four ligands, two receptors, and a binding protein. Its well-known role in the hypothalamic-pituitary-adrenal (HPA) axis is only one of many. The expression of CRH and its related peptides is widespread in peripheral tissue, with important functions in the immune system, energy metabolism, and female reproduction. For example, CRH is involved in the implantation of fertilized ova and in maternal tolerance to the fetus. An apparently unique adaptation has evolved in anthropoid primates: placental expression of CRH. Placental CRH stimulates the fetal adrenal zone, an adrenal structure unique to primates, to produce dehydroepiandrosterone sulfate (DHEAS), which is converted to estrogen by the placenta. Cortisol induced from the fetal and maternal adrenal glands by placental CRH induces further placental CRH expression, forming a positive feedback system that results in increasing placental production of estrogen. In humans, abnormally high placental expression of CRH is associated with pregnancy complications (e.g., preterm labor, intrauterine growth restriction (IUGR), and preeclampsia). Within anthropoid primates, there are at least two patterns of placental CRH expression over gestation: monkeys differ from great apes (and humans) by having a midgestational peak in CRH expression. The functional significance of these differences between monkeys and apes is not yet understood, but it supports the hypothesis that placental CRH performs multiple roles during gestation. A clearer understanding of the diversity of patterns of placental CRH expression among anthropoid primates would aid our understanding of its role in human pregnancy.
促肾上腺皮质激素释放激素（CRH）是一种古老的调节分子。CRH激素家族至少有四种配体、两种受体和一种结合蛋白。它在下丘脑 - 垂体 - 肾上腺（HPA）轴中广为人知的作用只是其众多功能之一。CRH及其相关肽在外周组织中广泛表达，在免疫系统、能量代谢和雌性生殖中具有重要功能。例如，CRH参与受精卵的着床以及母体对胎儿的耐受性。在类人猿灵长类动物中进化出了一种明显独特的适应性变化：胎盘表达CRH。胎盘CRH刺激胎儿肾上腺区，这是灵长类动物特有的肾上腺结构，以产生硫酸脱氢表雄酮（DHEAS），后者被胎盘转化为雌激素。胎盘CRH诱导胎儿和母体肾上腺产生的皮质醇进一步诱导胎盘CRH表达，形成一个正反馈系统，导致胎盘雌激素产量增加。在人类中，胎盘CRH异常高表达与妊娠并发症（如早产、宫内生长受限（IUGR）和先兆子痫）有关。在类人猿灵长类动物中，妊娠期间胎盘CRH表达至少有两种模式：猴子与大猩猩（和人类）不同，其CRH表达在妊娠中期达到峰值。猴子和猿类之间这些差异的功能意义尚不清楚，但它支持了胎盘CRH在妊娠期间发挥多种作用的假说。更清楚地了解类人猿灵长类动物中胎盘CRH表达模式的多样性将有助于我们理解其在人类妊娠中的作用。
