Increased 11β-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 292; no. 3; pp. R1101 - R1109
• Main Authors: Nammi, Srinivas, Dembele, Korami, Nyomba, B. L. Grégoire
• Format: Journal Article
• Language: English
• Published: 01.03.2007
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00255.2006

Rat offspring prenatally exposed to alcohol display features of metabolic syndrome characterized by a low birth weight, catch-up growth, dyslipidemia, and insulin-resistant diabetes with increased gluconeogenesis, during adult life. Gluconeogenesis is partly regulated by cyclic AMP- and glucocorticoid-dependent mechanisms. Glucocorticoid action at the receptor level depends on its circulating concentrations and is amplified at the prereceptor level by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regenerates active glucocorticoids from inactive forms. To determine whether 11β-HSD1 is dysregulated in this rat model, we examined the expression and enzyme activity of 11β-HSD1 and its regulator enzyme hexose-6-phosphate dehydrogenase (H6PD) in the liver of postnatal day 7 (neonatal) and 3-mo-old (adult) rat offspring prenatally exposed to alcohol. Measurements of 11β-HSD1 and H6PD were also performed in the omental fat of adult rat offspring. In both neonatal and adult rats, prenatal alcohol exposure resulted in increased tissue corticosterone concentrations, increased expression, and oxoreductase activity of 11β-HSD1, and a parallel increase of H6PD expression. The data suggest that due to both transcriptional and posttranscriptional dysregulations, rats exposed to alcohol early in life have increased 11β-HSD1 activity, which may explain insulin-resistant diabetes in these animals later in life.