Revskoy S, Halasz I, Redei E
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA.
Endocrinology. 1997 Jan;138(1):389-96. doi: 10.1210/endo.138.1.4838.
The present study was carried out to investigate how hormonal changes caused by chronic alcohol exposure of rats during the late period of gestation are coordinated with neuroendocrine functions of the fetal thymus, namely thymic expression of CRH and POMC genes. Alcohol consumption by pregnant dams led to a 5-fold elevation of plasma corticosterone (CORT) levels and significantly decreased fetal CORT levels. This generally inverse correlation between maternal and fetal CORT was absent in alcohol-consuming dams and their male fetuses on day 19 of gestation. These day 19 fetuses also had an attenuated plasma testosterone surge that occurred in the male control (pair-fed) fetus on day 19 of embryonic life. Furthermore, fetal alcohol exposure (FAE) resulted in a significant increase in thymic CRH and a decrease in thymic POMC expression in the male fetuses only, specifically on embryonic day 19. Thus, the strong positive correlation between CRH and POMC gene expression in the thymus of pair-fed male and female FAE fetuses was abolished in the FAE males. However, regardless of embryonic age or treatment, a strong positive correlation between thymic POMC gene expression and plasma testosterone levels in the male fetuses was detected. These data suggest that the sexually dimorphic effect of FAE on the fetal thymic POMC and CRH expression in males is driven by testosterone and may be related, therefore, to the presence of alcohol at the time of the prenatal testosterone surge in the male fetuses.
本研究旨在探讨孕期晚期大鼠长期酒精暴露引起的激素变化如何与胎儿胸腺的神经内分泌功能相协调,即促肾上腺皮质激素释放激素(CRH)和阿片促黑皮素原(POMC)基因在胸腺中的表达。怀孕母鼠饮酒导致血浆皮质酮(CORT)水平升高5倍,同时胎儿CORT水平显著降低。在妊娠第19天,饮酒母鼠及其雄性胎儿中,母体和胎儿CORT之间通常存在的这种负相关关系并不存在。这些妊娠第19天的胎儿血浆睾酮激增也减弱,而在胚胎期第19天的雄性对照(配对喂养)胎儿中会出现这种激增。此外,胎儿酒精暴露(FAE)仅导致雄性胎儿胸腺CRH显著增加,胸腺POMC表达减少,具体发生在胚胎第19天。因此,在FAE雄性胎儿中,配对喂养的雄性和雌性FAE胎儿胸腺中CRH和POMC基因表达之间的强正相关关系被消除。然而,无论胚胎年龄或处理方式如何,在雄性胎儿中均检测到胸腺POMC基因表达与血浆睾酮水平之间存在强正相关关系。这些数据表明,FAE对雄性胎儿胸腺POMC和CRH表达的性别差异效应是由睾酮驱动的,因此可能与雄性胎儿产前睾酮激增时酒精的存在有关。