title: Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA.
abstract: Moderately elevated maternal cortisol levels late in gestation cause enlargement of the fetal sheep heart. We have used quantitative real-time PCR to examine expression of candidate genes in fetal hearts from mothers in whom cortisol levels were increased (by infusion of 1 mg cortisol.kg(-1).day(-1)) or decreased (by adrenalectomy and replacement to 0.5 mg cortisol.kg(-1).day(-1)) from 115 to 130 days gestation. Control ewes were not treated with steroid. Expression of mineralocorticoid receptor (MR), glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and -2), IGF I and II, IGF receptors 1 and 2 (IGF-1R and IGF-2R), endothelial nitric oxide synthase, VEGF, myotrophin, angiotensinogen, the angiotensin receptors 1 and 2 (AT1R and AT2R), and the angiotensin converting enzymes 1 and 2 were measured. MR mRNA abundance in fetal hearts was found to be similar to that in adult kidney and hippocampus. Although there were no significant changes in most genes, 11beta-HSD2 and IGF-1R expression were significantly decreased in the high cortisol group and 11beta-HSD2 expression negatively correlated to left ventricular wall thickness. There was also a significant change in the ratio of AT receptor expression, with increased AT2R and decreased AT1R in the high cortisol group. MR, GR, and 11beta-HSD1 immunoreactivity was found in cardiomyocytes and cardiac blood vessels in 126-128 day fetal sheep; in contrast 11beta-HSD2 staining was predominantly in blood vessels. These results indicate that cortisol could indeed act in the fetal heart to induce enlargement and suggest that the renin-angiotensin system may play a role.
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610-0487, USA.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Reini
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
authors.forename: Ellen
authors.initials: E
authors.lastname: Jensen
authors.forename: Maureen
authors.initials: M
authors.lastname: Keller-Wood
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006321:Heart / Q000196:embryology*; D006854:Hydrocortisone / Q000097:blood*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012756:Sheep
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone