Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes:: Evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor γ2
Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes:: Evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor γ2
复制标题
DOI：
10.1210/en.141.2.649
复制
发表时间：
2000-02-01
期刊：
影响因子：
4.8
通讯作者：
Giudicelli, Y
中科院分区：
文献类型：
--
作者：
Dieudonne, MN;Pecquery, R;Giudicelli, Y
为了研究性类固醇激素在脂肪组织发育和分布中的作用，我们在体外研究了各种性类固醇（睾酮、二氢睾酮（DHT）和 19 β-雌二醇）对大鼠深层（附睾和宫旁）和浅表（股骨 SC）脂肪沉积的前脂肪细胞增殖和分化过程的影响。当铺板后第1天至第4天测定时，无论培养基中是否存在FCS，所有添加的类固醇均未能影响雄性大鼠前脂肪细胞的生长速率。相反，在雌性大鼠的前脂肪细胞中，我们观察到17β-雌二醇（0.01μM）对皮下的增殖能力有积极作用（x2），但对宫旁前脂肪细胞没有作用。当前脂肪细胞在分化过程中暴露于睾酮或DHT（0.1μM）时，仅附睾前脂肪细胞的8-磷酸甘油脱氢酶活性显着降低。当雄性大鼠的前脂肪细胞暴露于17β-雌二醇（0.01μM）时，前脂肪细胞的分化能力没有改变。然而，在来自卵巢切除雌性大鼠的宫旁前脂肪细胞中，17β-雌二醇显着增加（x1.34）甘油3-磷酸脱氢酶活性。在暴露于性类固醇的分化前脂肪细胞中，过氧化物酶体增殖物激活受体γ2的表达被17β-雌二醇上调，但不被雄激素上调。正如其他细胞类型中所述，性类固醇调节前脂肪细胞中胰岛素生长因子 1 受体 (IGF1R) 的表达。事实上，在雌性卵巢切除大鼠的皮下前脂肪细胞中，17β-雌二醇（0.01μM）可以增强IGF1R水平，而在附睾前脂肪细胞中，IGF1R水平可以通过DHT（0.01μM）而降低。通过同时暴露于雄激素或雌激素受体拮抗剂可以逆转这些作用。总之，这项研究表明，在原代培养并长期暴露于性激素的大鼠前脂肪细胞中，雄激素会引起抗脂肪生成作用，而雌激素则表现为促脂肪生成激素。此外，我们的结果表明，这些相反的作用可能与 IGF1R（雄激素和雌激素）和过氧化物酶体增殖物激活受体 γ 2 表达（雌激素）的变化有关。
To investigate the role of sex steroid hormones in adipose tissue development and distribution, we have studied the effect of various sex steroids (testosterone, dihydrotestosterone (DHT), and 19 beta-estradiol) in vitro, on the proliferation and differentiation processes in rat preadipocytes from deep (epididymal and parametrial) and superficial(femoral sc) fat deposits. All added steroids failed to affect the growth rate of preadipocytes from male rats when determined from day 1 to day 4 after plating, whether FCS was present or not in the culture medium. In contrast, in preadipocytes from female rats, we observed a positive effect (x2) of 17 beta-estradiol(0.01 mu M) on the proliferative capacities of sc but not parametrial preadipocytes. When preadipocytes were exposed to testosterone or DHT (0.1 mu M) during the differentiation process, the glycerol 8-phosphate dehydrogenase activity was significantly decreased in epididymal preadipocytes only. When preadipocytes from male rats were exposed to 17 beta-estradiol (0.01 mu M), the differentiation capacities of preadipocytes were not modified. However, in parametrial preadipocytes from ovariectomized female rats, 17 beta-estradiol significantly increased (x1.34) the glycerol 3-phosphate dehydrogenase activity. In differentiated preadipocytes that had been exposed to sex steroids, expression of peroxisome proliferator-activated receptor gamma 2 was up-regulated by 17 beta-estradiol but not by androgens. As described in other cell types, sex steroids modulate insulin growth factor 1 receptor (IGF1R) expression in preadipocytes. Indeed, IGF1R levels were either enhanced by 17 beta-estradiol (0.01 mu M) in sc preadipocytes from female ovariectomized rats or decreased by DHT (0.01 mu M ) in epididymal preadipocytes. These effects were reversed by simultaneous exposure to androgen or estrogen receptor antagonists. In conclusion, this study demonstrates that, in rat preadipocytes kept in primary culture and chronically exposed to sex hormones, androgens elicit an antiadipogenic effect, whereas estrogens behave as proadipogenic hormones. Moreover, our results suggest that these opposite effects could be related to changes in IGF1R (androgens and estrogens) and peroxisome proliferator-activated receptor gamma 2 expression (estrogens).