SEX-SPECIFIC EFFECTS OF GROWTH HORMONE ON HEPATIC 11 Β-Hydroxysteroid DEHYDROGENASE ACTIVITY AND GENE EXPRESSION IN HYPOTHYROID RATS

Liu, Yanjun; Nakagawa, Yuichi; Toya, Kazuhiko; Ozeki, Takehiko

doi:10.1016/s0024-3205(97)00389-5

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…The 11␤-HSD1 isozyme expresses stable dehydrogenase activity (converting corticosterone [B] to 11-dehydrocorticosterone [A]), which reflects 11␤-HSD1 protein levels and reductase activity in vivo (18,20). Thus, we measured 11␤-dehydrogenase activity in liver as previously reported (31)(32)(33). Briefly, liver was homogenized in Krebs-Ringer buffer solution at 4°C in a Dounce tissue grinder.…”

Section: Methodsmentioning

confidence: 99%

Leptin Activation of Corticosterone Production in Hepatocytes May Contribute to the Reversal of Obesity and Hyperglycemia in Leptin-Deficient ob/ob Mice

et al. 2003

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Glucocorticoids have been implicated as pathophysiological mediators of obesity and insulin resistance and are regulated by 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1). This enzyme regenerates active corticosterone from inactive 11-keto forms. To assess the role of 11␤-HSD1-mediated synthesis of active corticosterone in leptin-related obesity and diabetes, we examined the peripheral effect of leptin on 11␤-HSD1 activity and gene expression in vivo and in vitro in hepatocytes from ob/ob mice and in liver of streptozotocin (STZ)-treated ob/ob mice. We observed an inverse relationship between hepatic 11␤-HSD1 expression and body weight in ob/ob mice and lean littermates. Leptin treatment of ob/ob mice markedly increased hepatic 11␤-HSD1 activity and mRNA expression. This induction of 11␤-HSD1 expression corresponded to reduced levels of circulating corticosterone and weight loss in ob/ob mice treated with leptin, indicating that impaired hepatic 11␤-HSD1 expression may contribute to the pathogenesis of obesity in ob/ob mice. In addition, leptin treatment of STZ-treated ob/ob mice caused marked increases in hepatic 11␤-HSD1 levels associated with decreased body weight and a significant reduction in hyperglycemia due to pancreatic ␤-cell damage. Addition of leptin to ob/ob mouse primary hepatocytes led to a dose-dependent increase in 11␤-HSD1 mRNA expression. In contrast, leptin did not influence 11␤-HSD1 expression in primary hepatocytes from db/db mice, indicating that leptin regulation of 11␤-HSD1 expression is probably mediated by the functional leptin receptor. Thus, leptin appears to be an important metabolic signal that directly activates intrahepatic corticosterone production. These findings suggest that the liverspecific interaction of leptin with 11␤-HSD1 is involved in the development of obesity and insulin resistance in ob/ob mice.

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Section: Methodsmentioning

confidence: 99%

Leptin Activation of Corticosterone Production in Hepatocytes May Contribute to the Reversal of Obesity and Hyperglycemia in Leptin-Deficient ob/ob Mice

et al. 2003

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“…Total RNA was isolated from liver and adipose tissue with a single-step guanidine isothiocyanate acid-phenol chloroform extraction procedure, as described previously (Liu et al, 1997). The expression levels of specific mRNAs were quantified using quantitative fluorescent real-time PCR.…”

Section: Rna Isolation and Analysismentioning

confidence: 99%

“…However, under in vitro conditions in homogenized tissues, the dehydrogenase activity (converting corticosterone to 11-dehydrocorticosterone; 11-DHC) is more stable, and reflects the 11β-HSD1 reductase activity in vivo (Seckl and Walker, 2001;Rask et al, 2001;Livingstone et al, 2000a,b). Thus, we measured the 11β-dehydrogenase activities as previously reported (Liu et al, 1997;Morton et al, 2004). Tissues were dissected and homogenized in Krebs-Ringer buffer (KRB) solution at 4°C.…”

Section: β-Hsd1 Enzyme Activity Assay and Tissue Corticosterone Meamentioning

confidence: 99%

Diabetic pregnancy in rats leads to impaired glucose metabolism in offspring involving tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 expression

Fujisawa

Nakagawa

et al. 2007

Life Sciences

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“…Total RNA was isolated from rat placentas and fetal kidneys with a single-step guanidinium isothiocyanate acid-phenol chloroform extraction procedure described previously (Liu et al, 1997). For Northern blotting, 30 Ag of total RNA/lane were elecrophoresed and transferred overnight onto nylon membranes (Hybond-XL, Amersham Pharmacia Biotech, U.K.) by capillary action.…”

Section: Northern Blot Analysesmentioning

confidence: 99%

Streptozotocin-induced diabetes in the pregnant rat reduces 11 beta-hydroxysteroid dehydrogenase type 2 expression in placenta and fetal kidney

Fujisawa¹,

Nakagawa²,

Li³

et al. 2004

Life Sciences

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Several epidemiological and animal studies have shown that the offsprings of diabetic mothers have higher incidences of glucose intolerance, obesity, insulin resistance, and hypertension in later life. It is well known that glucocorticoid metabolism plays a crucial role on several adult disease originated from fetal environment. The aim of this study was to investigate the relation between diabetic pregnancy and glucocorticoid metabolism of both mother and fetus, focusing on the 11 beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2. A model of diabetic pregnancy was made by intravenous injection of streptozotocin (35 mg/kg body weight) to Sprague-Dawley rats, and blood and tissue samples were collected on day 20 of pregnancy. In the diabetic group, expression of 11 beta-hydroxysteroid dehydrogenase type 2 in placentas and fetal kidneys was decreased remarkably. Corticosterone levels of diabetic mothers were lower than those of control rats. Despite the differences in maternal corticosterone levels, fetal levels of corticosterone did not differ between the groups. Our results lend support to the concept that diabetic pregnancy imprints glucocorticoid regulation in these fetuses, which may contribute to their increased incidence of higher blood pressure as adults.

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SEX-SPECIFIC EFFECTS OF GROWTH HORMONE ON HEPATIC 11 Β-Hydroxysteroid DEHYDROGENASE ACTIVITY AND GENE EXPRESSION IN HYPOTHYROID RATS

Cited by 10 publications

References 38 publications

Leptin Activation of Corticosterone Production in Hepatocytes May Contribute to the Reversal of Obesity and Hyperglycemia in Leptin-Deficient ob/ob Mice

Leptin Activation of Corticosterone Production in Hepatocytes May Contribute to the Reversal of Obesity and Hyperglycemia in Leptin-Deficient ob/ob Mice

Diabetic pregnancy in rats leads to impaired glucose metabolism in offspring involving tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 expression

Streptozotocin-induced diabetes in the pregnant rat reduces 11 beta-hydroxysteroid dehydrogenase type 2 expression in placenta and fetal kidney

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