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Steroids. 1997 Jan;62(1):89-94.

Glucocorticoids, feto-placental 11 beta-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease.

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  • Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Scotland.

Abstract

Increasing human epidemiological data suggest that events that subtly retard intrauterine growth may determine common disorders, such as hypertension and non-insulin-dependent diabetes, in adult life. The underlying mechanisms are unknown. However, excessive fetal exposure to glucocorticoids retards growth and "programs" adult hypertension in rats. 11 beta-Hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) catalyzes the rapid inactivation of cortisol and corticosterone to inert 11 keto-products. Normally, 11 beta-HSD2 in the placenta and some fetal tissues is thought to protect the fetus from excess maternal glucocorticoids. In both rats and humans there is considerable natural variation in placental 11 beta-HSD2, and enzyme activity correlates with birth weight. Moreover, inhibition of feto-placental 11 beta-HSD2 in the rat reduces birth weight and produces hypertensive and hyperglycaemic adult offspring, many months after prenatal treatment; effects are dependent upon intact maternal adrenals, suggesting a direct action on the fetus or placenta. Maternal protein restriction during pregnancy also produces hypertensive offspring and selectively attenuates placental 11 beta-HSD2 activity. These data suggest that feto-placental 11 beta-HSD2, by regulating fetal exposure to maternal glucocorticoids, crucially determines fetal growth and the programming of later disorders. Deficiency of the barrier to maternal glucocorticoids may represent a common pathway between the maternal environment and feto-placental programming of later disease. These data may, at least in part, explain the human observations linking early life events to the risk of subsequent disease.

PMID:
9029721
[PubMed - indexed for MEDLINE]
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