Age Characteristics Of Adipose Tissue Mrna Expression Of 11¦Â Hydroxysteroid Dehydrogenase Type 1 And Site-specific Regulation

The adiposity and distribution of adipose tissue are dependent on age and sex. Glucocorticoids and sex hormones may involve in the proliferation and distribution of adipose tissue. However, the exact molecular mechanism remains unclear. 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) is an enzyme which converts inactive cortisone to active cortisol in local tissue. Cortisol can inhibit adipocyte proliferation and promote adipocyte differentiation and fat accumulation. We hypothesis that the adiposity and distribution of adipose tissue are related to 11βHSD1 mRNA expression, and sex hormones may affect the distribution of adipose tissue via 11βHSD1 .Therefore, we observed the expression of 11βHSD1 mRNA in abdominal subcutaneous (Sc) and omental (Om) adipose tissue of the girls, pre- and postmenopausal women, and explored the relationship between 11βHSD1 mRNA expression and adiposity and distribution of adipose tissue in different periods. Moreover, we observed the effect of sex hormones (androgen and estrogen) on the expression of 11βHSD1 mRNA in Sc and Om adipose tissue of the pre- and post-menopausal women in vitro culture, and explored the molecular mechanism of the redistribution of body fat after menopause, which might be contribute to clinical intervention and treatment of central obesity and metabolic syndrome.Part one: The expression of 11βHSD1 mRNA in adipose tissues of girls and womenObjective: To observe the expression of 11βHSD1 mRNA in abdominal Sc and Om adipose tissue of the girls, pre- and postmenopausal women, and to explore the molecular mechanism of the accumulation and distribution of adipose tissue in different ages of human.Method: Sc and Om adipose tissue were obtained from 11 girls (age: 5.64±3.72 years ), 13 premenopausal women (age:33.24±6.25 years)and 7 postmenopausal women (age: 64.57±7.76 years). BMI, WHR, blood glucose and lipid of the objects were determined. The expression of 11βHSD1 and adiponectin mRNA in paired adipose tissues were measured by real time PCR. 11βHSD1 enzyme activity in adipose tissue was detected by radioimmunoassay.Result: 11βHSD1 mRNA expression in Sc and Om adipose tissue of the girls was significantly lower than that of the premenopausal (Sc: P=0.001; Om: P=0.005)and postmenopausal women (Sc: P=0.000; Om: P=0.000), and 11βHSD1 mRNA expression in the premenopausal women was significantly lower than that of the postmenopausal women (Sc :P=0.000; Om: P=0.000), and 11βHSD1 enzyme activity in Om adipose tissue is consistent with the mRNA expression. The expression of 11βHSD1 mRNA in Om adipose tissue was higher compared to Sc adipose tissue in the postmenopausal group (P=0.018). Further, the expression of 11βHSD1 mRNA in Om adipose tissue of premenopausal women (r = 0.856, P = 0.03) and the postmenopausal women (r = 0.900, P = 0.037) was positively correlated with WHR (Waist Hip Ratio), respectively. In contrast to 11βHSD1, adiponectin mRNA expression in Om adipose tissue of the girls was significantly higher than that of the postmenopausal group (P=0.002) and the premenopausal group (P=0.018). The expression of 11βHSD1 mRNA was negatively correlated with adiponectin mRNA expression in Om adipose tissue of all subjects (r =- 0.485, P = 0.005).Conclusion: The 11βHSD1 mRNA expression in adipose tissue were increased with age and was positively correlated with WHR of adult females, which suggested that it possibly involved in the accumulation and distribution of human adipose tissue. Part two: The depot-specific regulation of sex hormones on 11βHSD1 mRNA expression in adipose tissueObjective: To observe the depot-specific regulation of sex hormones on 11βHSD1 mRNA expression in adipose tissue of pre- and post-menopausal women.Method: Sc and Om adipose tissue were obtained from 6 pre-menopausal women (age: 29.83±3.43 years ) and 16 postmenopausal women (age: 65.19±6.81 years).Pieces of adipose tissue were incubated with estrogen or testosterone for 24h.The expression of 11βHSD1 and adiponectin mRNA in paired adipose tissues were measured by real time PCR.Results: Estrogen increased 11βHSD1 mRNA expression in Om adipose tissue of pre-menopausal women by 2 fold (P=0.049), and increased 11βHSD1 mRNA expression in Sc adipose tissue by 1.9 fold (P=0.048) but decreased 11βHSD1 mRNA expression in Om adipose tissue by 30% of post-menopausal women (P=0.03). Androgen decreased 11βHSD1 mRNA expression in Sc adipose tissue of pre-menopausal women by 40% (P=0.034), and up-regulated 11βHSD1 mRNA expression in Om adipose tissue of post-menopausal women by 1.9 fold (P=0.005).Conclusion: The sex hormones stimulate 11βHSD1 mRNA expression in adipose tissue in age and depot-specific pattern, which may be important molecular mechanism of distribution of body fat in pre- and postmenopausal women.