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Departments of Physiology and Obstetrics and Gynecology (J.S.R.), University of Adelaide, Adelaide, South Australia 5005, Australia
Address all correspondence and requests for reprints to: Dr. I. C. McMillen, Department of Physiology, Medical School Building, University of Adelaide, G.P.O. Box 498, North Terrace, Adelaide, South Australia 5005, Australia. E-mail: caroline.mcmillen{at}adelaide.edu.au
We have investigated the effects of fetal growth restriction, induced by restriction of placental growth and function (PR), on 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD-1) and 11ßHSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. Fetal liver, kidney, and adrenals were collected from normally grown fetuses at 90 days (n = 6), 125 days (n = 6), and 141145 days (n = 7) and from PR fetuses at 141145 days (n = 6). Expression of 11ßHSD-1 mRNA in the fetal liver increased significantly between 125 days (7.4 ± 0.8) and 141145 days gestation (27 ± 5.3). There was also an approximately 2-fold increase in the ratio of 11ßHSD-1 mRNA/18S rRNA expression in the PR group (53.8 ± 7.9) compared with that in control animals at 141145 days gestation. There was a significant decrease in 11ßHSD-2 mRNA in fetal adrenals between 125 days (41.6 ± 2.4) and 141145 days (26.7 ± 1.1) gestation, but there was no effect of PR on the expression of adrenal 11ßHSD-2 mRNA. 11ßHSD-2 mRNA expression in the fetal kidney increased between 90 days (16.8 ± 1.7) and 141145 days gestation (31.7 ± 4.3), but there was no effect of PR on the levels of 11ßHSD-2 mRNA in the fetal kidney. In summary, 11ßHSD-2 mRNA is differentially regulated in the fetal adrenal and kidney in the sheep fetus during late gestation. There is also a specific increase in the expression of 11ßHSD-1 mRNA in the liver of growth-restricted fetuses in late gestation. This suggests that there is increased hepatic exposure to cortisol in the growth-restricted fetus, which may be important in the reprogramming of hepatic physiology that occurs after growth restriction in utero.
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