Xu X, De Pergola G, Eriksson P S, Fu L, Carlsson B, Yang S, Edén S, Björntorp P
Wallenberg Laboratory, University of Göteborg, Sweden.
Endocrinology. 1993 Apr;132(4):1651-7. doi: 10.1210/endo.132.4.8384992.
In the previous studies we have shown that testosterone increases lipolytic responsiveness to catecholamines in rat white adipocytes, and that is associated with an up-regulation of beta-adrenergic receptor density. However, the postreceptor events involved in the testosterone induced enhancement of beta-adrenergic receptor activated lipolysis in these cells have not been adequately studied, and were therefore investigated in the present study. Male Sprague Dawley rats were divided into three groups: control, castrated, and castrated treated with testosterone. The beta-adrenergic receptor-mediated cAMP accumulation, measured with RIA after isoproterenol (a beta-adrenergic agonist) stimulation was decreased in castrated rats, and reversed by testosterone treatment, suggesting a testosterone effect at or proximal to adenylate cyclase. However, no differences between the groups were found in abundance of G alpha protein messenger RNAs (G alpha s, G alpha i-1, and G alpha i-2) as analyzed by Northern blot and a solution hybridization RNase protection assay, or in G protein mass measured with a quantitative enzyme-linked immunosorbent assay in fat cell membrane preparation. Lipolysis stimulated by N6-monobutyryl-cAMP was reduced in castrated rats and recovered by testosterone treatment, suggesting that components distal to the adenylate cyclase, i.e. protein kinase A (PKA) and/or hormone sensitive lipase (HSL) also are involved in testosterone regulation of lipolysis. In conclusion, these and previous results suggest that the testosterone-induced increase in lipolytic response to catecholamines in rat white adipocytes is mediated through several events including an increased beta-adrenergic receptor density, probably an increased adenylate cyclase activity and an increased protein kinase A/hormone sensitive lipase activity at the postreceptor level with apparent absence of effect on the expression of G-proteins.
在先前的研究中，我们已经表明，睾酮可增强大鼠白色脂肪细胞对儿茶酚胺的脂解反应性，且这与β-肾上腺素能受体密度的上调有关。然而，睾酮诱导这些细胞中β-肾上腺素能受体激活的脂解增强所涉及的受体后事件尚未得到充分研究，因此在本研究中进行了调查。雄性Sprague Dawley大鼠被分为三组：对照组、去势组和去势后用睾酮处理组。用放射性免疫分析法（RIA）测定异丙肾上腺素（一种β-肾上腺素能激动剂）刺激后β-肾上腺素能受体介导的环磷酸腺苷（cAMP）积累，结果显示去势大鼠中该积累减少，而睾酮处理可使其恢复，这表明睾酮在腺苷酸环化酶或其近端起作用。然而，通过Northern印迹法和溶液杂交核糖核酸酶保护试验分析，各组之间在Gα蛋白信使核糖核酸（Gαs、Gαi - 1和Gαi - 2）的丰度上，或在脂肪细胞膜制备物中用定量酶联免疫吸附测定法测量的G蛋白量方面，均未发现差异。N6 - 单丁酰 - cAMP刺激的脂解在去势大鼠中降低，而睾酮处理可使其恢复，这表明腺苷酸环化酶远端的成分，即蛋白激酶A（PKA）和/或激素敏感性脂肪酶（HSL）也参与了睾酮对脂解的调节。总之，这些以及先前的结果表明，睾酮诱导的大鼠白色脂肪细胞对儿茶酚胺脂解反应的增加是通过多种事件介导的，包括β-肾上腺素能受体密度增加、可能的腺苷酸环化酶活性增加以及受体后水平上蛋白激酶A/激素敏感性脂肪酶活性增加，而对G蛋白的表达显然没有影响。
