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

Placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) conver ts glucocorticoids to 11-keto-products and is believed to play an important role in protecting fetuses from higher maternal glucocorticoid levels. Rec ent reports have speculated that prenatal glucocorticoid exposure leads to fetal growth retardation and adult offspring hypertension and hyperglycemia . To investigate the effects of placental 11 beta-HSD2 inhibition on glucos e metabolism and the 11 beta-HSD system in adult offspring, pregnant rats w ere treated with daily injections of carbenoxolone (CBX), an inhibitor of 1 1 beta-HSD. The offspring of the maternal CBX treatment group showed reduce d 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 A l, 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 11 beta-HSD1 and renal 11 beta-HSD1 was decreased 87. 6% (P <.05) and 52.3% (P <.01) in adult offspring of the maternal CBX treat ment group, whereas renal 11 beta-HSD1 was not significantly altered. The c hange in 11 beta-HSD activity corresponded to the change in the gene expres sion. These results suggest that inhibition of placental 11 beta-HSD2 cause s growth retardation, glucose intolerance, and partial suppression of the 1 1 beta-HSD, system in the offspring. Copyright (C) 1999 by W.B, Saunders Co mpany.