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

Christopher J McNeil, Margaret O Nwagwu, Angela M Finch, Kenneth R Page, Alan Thain, Harry J McArdle, Cheryl J Ashworth

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30 Citations (Scopus)

Abstract

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 11beta-hydroxysteroid dehydrogenase-isoform 2 (11beta 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 11beta-hydroxysteroid dehydrogenase-isoform 1 (11beta HSD-1) gene expression. We found that fetal organs have different temporal patterns of 11beta 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.
Original languageEnglish
Pages (from-to)653-661
Number of pages9
JournalReproduction
Volume133
Issue number3
DOIs
Publication statusPublished - 1 Mar 2007

Keywords

  • 11-beta-hydroxysteroid dehydrogenase type 1
  • 11-beta-hydroxysteroid dehydrogenase type 2
  • 11-beta-hydroxysteroid dehydrogenases
  • adrenocorticotropic hormone
  • animals
  • biological markers
  • blotting, Northern
  • body weight
  • female
  • fetal blood
  • fetal development
  • gene expression
  • gestational age
  • hydrocortisone
  • liver
  • maternal-fetal exchange
  • models, biological
  • pituitary-adrenal system
  • pregnancy
  • RNA, messenger
  • receptors, glucocorticoid
  • reverse transcriptase polymerase chain reaction
  • swine

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