This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McNeil, C. J Articles by Ashworth, C. J Search for Related Content PubMed PubMed Citation Articles by McNeil, C. J Articles by Ashworth, C. J

Glucocorticoid exposure and tissue gene expression of 11ß HSD-1, 11ß HSD-2, and glucocorticoid receptor in a porcine model of differential fetal growth

Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK, ¹ School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK and ² Sustainable Livestock Systems Group, Scottish Agricultural College, Roslin BioCentre, Roslin, Midlothian EH25 9PS, UK

Correspondence should be addressed to C J Ashworth; Email: cheryl.ashworth{at}sac.ac.uk

Glucocorticoids play a critical role in fetal development, but inappropriate exposure is associated with reduced fetal growth. We investigated cortisol exposure and supply in a porcine model of differential fetal growth. This model compares the smallest fetus of a litter with an average-sized sibling at three stages of gestation. At day 45, small fetuses had reduced plasma cortisol (16.8 ± 3.4 ng/ml) relative to average fetuses (34.4 ± 3.4 ng/ml, P < 0.001). At day 65 levels had reduced in small and average fetuses to similar concentrations (5.7 ± 1.0 vs 4.8 ± 0.5 ng/ml, P = 0.128). By day 100, elevated levels were found in small fetuses (10.7 ± 1.5 vs 7.6 ± 0.7 ng/ml, P < 0.001). Maternal plasma cortisol was unchanged over gestation (day 45, 56.7 ± 21.6 ng/ml; day 65, 57.8 ± 14.4 ng/ml; day 100, 55.7 ± 6.5 ng/ml). We examined the cause of altered cortisol by investigating the fetal hypothalamic–pituitary–adrenal axis through the measurement of adrenocorticotropic hormone and assessing exposure to maternal cortisol by quantifying placental 11ß-hydroxysteroid dehydrogenase-isoform 2 (11ß HSD-2) gene expression. These data suggest that altered cortisol supply was of fetal origin. We examined organ glucocorticoid (GC) metabolism by the measurement of GC receptor (GR) and 11ß-hydroxysteroid dehydrogenase-isoform 1 (11ß HSD-1) gene expression. We found that fetal organs have different temporal patterns of 11ß HSD-1 and GR expression, with the liver particularly sensitive to cortisol in late gestation. This study examines GC exposure in naturally occurring differential growth and simultaneously explores tissue GC sensitivity and handling, at three key stages of gestation.