Elsevier

Metabolism

Volume 48, Issue 12, December 1999, Pages 1584-1588
Metabolism

Influence of placental 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibition on glucose metabolism and 11β-HSD regulation in adult offspring of rats

https://doi.org/10.1016/S0026-0495(99)90249-4Get rights and content

Abstract

Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) converts glucocorticoids to 11-keto-products and is believed to play an important role in protecting fetuses from higher maternal glucocorticoid levels. Recent reports have speculated that prenatal glucocorticoid exposure leads to fetal growth retardation and adult offspring hypertension and hyperglycemia. To investigate the effects of placental 11β-HSD2 inhibition on glucose metabolism and the 11β-HSD system in adult offspring, pregnant rats were treated with daily injections of carbenoxolone (CBX), an inhibitor of 11β-HSD. The offspring of the maternal CBX treatment group showed reduced birth weight (treated v control, 5.6 ± 0.5 v 6.4 ± 0.4 g, P < .0001). In adult offspring of the maternal CBX treatment group, plasma hemoglobin A1c was significantly increased (7.3% ± 1.8% v 4.8% ± 0.3%, P < .01) and glucose intolerance was shown on the oral glucose tolerance test. The gene expression of hepatic 11β-HSD1 and renal 11β-HSD2 was decreased 87.6% (P < .05) and 52.3% (P < .01) in adult offspring of the maternal CBX treatment group, whereas renal 11β-HSD1 was not significantly altered. The change in 11β-HSD activity corresponded to the change in the gene expression. These results suggest that inhibition of placental 11β-HSD2 causes growth retardation, glucose intolerance, and partial suppression of the 11β-HSD system in the offpsring.

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