McGillick Erin V, Orgeig Sandra, McMillen I Caroline, Morrison Janna L
Early Origins of Adult Health Research Group, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001 ; Molecular & Evolutionary Physiology of the Lung Laboratory, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001.
Molecular & Evolutionary Physiology of the Lung Laboratory, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001.
Physiol Rep. 2013 Nov;1(6):e00130. doi: 10.1002/phy2.130. Epub 2013 Nov 11.
The prepartum surge in plasma cortisol concentrations in humans and sheep promotes fetal lung and surfactant system maturation in the support of air breathing after birth. This physiological process has been used to enhance lung maturation in the preterm fetus using maternal administration of betamethasone in the clinical setting in fetuses as young as 24 weeks gestation (term = 40 weeks). Here, we have investigated the impact of fetal intravenous cortisol infusion during the canalicular phase of lung development (from 109- to 116-days gestation, term = 150 ± 3 days) on the expression of genes regulating glucocorticoid (GC) activity, lung liquid reabsorption, and surfactant maturation in the very preterm sheep fetus and compared this to their expression near term. Cortisol infusion had no impact on mRNA expression of the corticosteroid receptors (GC receptor and mineralocorticoid receptor) or HSD11B-2, however, there was increased expression of HSD11B-1 in the fetal lung. Despite this, cortisol infusion had no effect on the expression of genes involved in lung sodium (epithelial sodium channel -α, -β, or -γ subunits and sodium-potassium ATPase-β1 subunit) or water (aquaporin 1, 3, and 5) reabsorption when compared to the level of expression during exposure to the normal prepartum cortisol surge. Furthermore, in comparison to late gestation, cortisol infusion does not increase mRNA expression of surfactant proteins (SFTP-A, -B, and -C) or the number of SFTP-B-positive cells present in the alveolar epithelium, the cells that produce pulmonary surfactant. These data suggest that there may be an age before which the lung is unable to respond biochemically to an increase in fetal plasma cortisol concentrations.
人类和绵羊产前血浆皮质醇浓度的激增可促进胎儿肺和表面活性剂系统成熟，以支持出生后的呼吸。这一生理过程已被用于通过在临床环境中给妊娠24周（足月为40周）的胎儿母亲注射倍他米松来促进早产胎儿的肺成熟。在此，我们研究了在肺发育小管期（妊娠109至116天，足月为150±3天）给极早产绵羊胎儿静脉输注皮质醇对调节糖皮质激素（GC）活性、肺液重吸收和表面活性剂成熟的基因表达的影响，并将其与足月时的表达进行比较。皮质醇输注对皮质类固醇受体（GC受体和盐皮质激素受体）或HSD11B - 2的mRNA表达没有影响，然而，胎儿肺中HSD11B - 1的表达增加。尽管如此，与暴露于正常产前皮质醇激增期间的表达水平相比，皮质醇输注对参与肺钠（上皮钠通道-α、-β或-γ亚基和钠钾ATP酶-β1亚基）或水（水通道蛋白1、3和5）重吸收的基因表达没有影响。此外，与妊娠晚期相比，皮质醇输注不会增加表面活性剂蛋白（SFTP - A、-B和-C）的mRNA表达，也不会增加肺泡上皮中产生肺表面活性剂的SFTP - B阳性细胞的数量。这些数据表明，可能存在一个年龄界限，在此之前肺无法对胎儿血浆皮质醇浓度的增加产生生化反应。
