Disease relevance of RNU1A3

• Increased adipocyte 11beta HSD-1 is a possible cause of visceral obesity in humans [1].
• At the cellular level, the enzyme hydroxysteroid dehydrogenase type 1 (HSD1) locally regenerates active cortisol from inactive cortisone, amplifying glucocorticoid receptor activation and promoting preadipocyte differentiation and adipocyte hypertrophy [2].

High impact information on RNU1A3

• H6PDH mRNA was also detected with a mean DeltaC(T) of 14.46 (range 13.13-16.60), approximately 35-fold more abundant than 11beta HSD-1 in skeletal muscle [3].
• 11beta HSD-1 oxoreductase activity was demonstrated, with mean conversion of cortisone to cortisol of 17.7% per 200 mg of muscle per 24 h (range 7.1-29.5%) [3].
• Measurements (i) 11beta HSD-1 and H6PDH mRNA expression by quantitative reverse transcription polymerase chain reaction (RT-PCR); (ii) protein localization and fibre type specificity by immunohistochemistry; and (iii) enzyme oxoreductase activity by percentage conversion of (3)H cortisone to cortisol [3].
• Although initial studies in transgenic mice and humans are encouraging, more data are required to conclusively prove the hypothesis that the adipose-tissue-specific overexpression of HSD1 and the resultant increase in tissue-specific cortisol concentrations result in human obesity, insulin resistance, high blood pressure, and metabolic syndrome [2].
• In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level [4].

Biological context of RNU1A3

• Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia [4].
• We examined organ glucocorticoid (GC) metabolism by the measurement of GC receptor (GR) and 11beta-hydroxysteroid dehydrogenase-isoform 1 (11beta HSD-1) gene expression [5].
• We found that fetal organs have different temporal patterns of 11beta HSD-1 and GR expression, with the liver particularly sensitive to cortisol in late gestation [5].
• Glucocorticoid exposure and tissue gene expression of 11{beta} HSD-1, 11{beta} HSD-2, and glucocorticoid receptor in a porcine model of differential fetal growth [5].

Associations of RNU1A3 with chemical compounds

• The enzyme 11beta hydroxysteroid dehydrogenase-1 (11beta HSD-1) regenerates active glucocorticoids from inactive glucocorticoids [1].
• Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl) [4].

References