De Marinis Elisabetta, Martini Chiara, Trentalance Anna, Pallottini Valentina
Department of Biology, University of Roma Tre, Viale Marconi, 446, 00146 Rome, Italy.
J Endocrinol. 2008 Sep;198(3):635-43. doi: 10.1677/JOE-08-0242. Epub 2008 Jul 4.
Physiological sex differences may influence metabolic status and then alter the onset of some diseases. According to recent studies, it is now well established that females are more protected from hypercholesterolemia-related diseases, such as cardiovascular diseases until menopause. Female protection from hypercholesterolemia is mediated by the hypolipidemic properties of estrogens, even if mechanisms underlying this protection remain still debated. Even though the regulatory mechanisms of cholesterol homeostasis maintenance are well known, few data are available on the supposed differences between male and female in these processes. So, the aim of this work was to define, through an in vivo study, the putative sex-dependent regulation of the processes underlying cholesterol homeostasis maintenance. We examined 3-hydroxy 3-methylglutaryl coenzyme A reductase and its regulatory protein network as well as the amount of low-density lipoprotein receptor and cholesterol. The study was conducted in the liver and plasma of male and female rats, on adults and during postnatal development, and on 17-beta-estradiol-treated male rats. Our data support that physiological differences in proteins involved in cholesterol balance are present between the sexes and, in particular, 3-hydroxy 3-methylglutaryl coenzyme A reductase shows lower activity and expression in female and 17-beta-estradiol-treated male rats than in adult untreated male. Our data suggest that sex differences in enzyme expression depend on variation in regulatory proteins and seem to be related to estrogen presence. This work adds new evidence in the complicated picture of sex-dependent cellular physiology and establishes a new role for reductase regulatory proteins as a link between estrogen protective effects and cholesterol homeostasis.
生理性别差异可能影响代谢状态，进而改变某些疾病的发病情况。根据最近的研究，目前已明确证实，在绝经前，女性对高胆固醇血症相关疾病（如心血管疾病）具有更强的抵抗力。女性对高胆固醇血症的保护作用是由雌激素的降血脂特性介导的，尽管这种保护作用的潜在机制仍存在争议。尽管胆固醇稳态维持的调节机制已为人所知，但关于男性和女性在这些过程中可能存在的差异的数据却很少。因此，本研究的目的是通过一项体内研究来确定胆固醇稳态维持过程中可能存在的性别依赖性调节。我们检测了3-羟基-3-甲基戊二酰辅酶A还原酶及其调节蛋白网络，以及低密度脂蛋白受体和胆固醇的含量。该研究在成年和出生后发育阶段的雄性和雌性大鼠的肝脏和血浆中进行，并对接受17-β-雌二醇治疗的雄性大鼠进行了检测。我们的数据支持两性在参与胆固醇平衡的蛋白质方面存在生理差异，特别是3-羟基-3-甲基戊二酰辅酶A还原酶在雌性和接受17-β-雌二醇治疗的雄性大鼠中的活性和表达低于未接受治疗的成年雄性大鼠。我们的数据表明，酶表达的性别差异取决于调节蛋白的变化，并且似乎与雌激素的存在有关。这项工作为复杂的性别依赖性细胞生理学图景增添了新的证据，并确立了还原酶调节蛋白作为雌激素保护作用与胆固醇稳态之间联系的新作用。
