Influence of placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inhibition on glucose metabolism and 11beta-HSD regulation in adult offspring of rats.
Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-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 11beta-HSD2 inhibition on glucose metabolism and the 11beta-HSD system in adult offspring, pregnant rats were treated with daily injections of carbenoxolone (CBX), an inhibitor of 11beta-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 11beta-HSD1 and renal 11beta-HSD2 was decreased 87.6% (P < .05) and 52.3% (P < .01) in adult offspring of the maternal CBX treatment group, whereas renal 11beta-HSD1 was not significantly altered. The change in 11beta-HSD activity corresponded to the change in the gene expression. These results suggest that inhibition of placental 11beta-HSD2 causes growth retardation, glucose intolerance, and partial suppression of the 11beta-HSD system in the offspring.
Saegusa
H
H
Department of Pediatrics, Hamamatsu University School of Medicine, Japan.
Nakagawa
Y
Y
Liu
Y J
YJ
Ohzeki
T
T
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D005947:Glucose; D002229:Carbenoxolone