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Alterations in placental 11ß-hydroxysteroid dehydrogenase (11ßHSD) activities and fetal cortisol:cortisone ratios induced by nutritional restriction prior to conception and at defined stages of gestation in ewes

Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK, ¹ Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK and ² Regional Endocrine Unit, Department of Chemical Pathology, Southampton General Hospital, Southampton SO9 4XY, UK

Correspondence should be addressed to A E Michael; Email: t.michael{at}rfc.ucl.ac.uk

In the placenta, cortisol is inactivated by NADP⁺- and NAD⁺-dependent isoforms of 11ß-hydroxysteroid dehydrogenase (11ßHSD). Decreased placental 11ßHSD activities have been implicated in intrauterine growth restriction (IUGR) and fetal programming of adult diseases. The objective of this study was to investigate whether placental 11ßHSD activities and fetal plasma cortisol:cortisone ratios could be affected by nutritional restriction of ewes (70% maintenance diet) throughout gestation, for specific stages of gestation, or prior to mating. Chronic nutritional restriction from day 26 of gestation onwards decreased NAD⁺-dependent 11ßHSD activities by 52 ± 4% and 45 ± 6% on days 90 and 135 of gestation respectively. Although the decreases in enzyme activities were associated with fetal IUGR, the cortisol:cortisone ratio in fetal plasma was unaffected by chronic nutritional restriction throughout pregnancy. Nutritional restriction confined to early (days 26–45), mid- (days 46–90) and late gestation (days 91–135), or the 30 days prior to mating, had no significant effect on NAD⁺-dependent, placental 11ßHSD activities, nor was there evidence of IUGR. However, nutritional restriction at each stage of pregnancy and prior to mating was associated with significant decreases in the fetal plasma cortisol:cortisone ratio (3.2 ± 0.7 in control fetuses; 1.0 to 1.6 in fetuses carried by nutritionally restricted ewes). We conclude that nutritional restriction of pregnant ewes for more than 45 consecutive days can significantly decrease NAD⁺-dependent placental 11ßHSD activities in association with IUGR. While the cortisol:cortisone ratio in fetal plasma is sensitive to relatively acute restriction of nutrient intake, even prior to mating, this ratio does not reflect direct ex vivo measurements of placental 11ßHSD activities.

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