Corticotropin-releasing hormone and proopiomelanocortin gene expression is altered selectively in the male rat fetal thymus by maternal alcohol consumption.
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.
Revskoy
S
S
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA. s-revskoy@nwu.edu
Halasz
I
I
Redei
E
E
D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D008297:Male; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013739:Testosterone / Q000097:blood; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D000431:Ethanol; D013739:Testosterone; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone