Milsted A, Marcelo M C, Turner M E, Ely D L
The University of Akron, Ohio 44325-3908, USA.
J Hypertens. 1998 Jun;16(6):823-8. doi: 10.1097/00004872-199816060-00013.
To evaluate whether renin and angiotensinogen gene expression in females from two strains of rats that share the same autosomes and X chromosomes differs. Female SHR/y rats have the parental Wistar-Kyoto rat autosomes and X chromosomes and have no chromosomes of spontaneously hypertensive rat origin; thus they are genetically equivalent to female Wistar-Kyoto rats.
Because these genes are regulated by steroid hormones, we investigated the effects of removal of estrogen (ovariectomy) and addition of androgen (testosterone implants) on three groups of female SHR/y rats and the parental rat strain Wistar-Kyoto rat with groups of intact (control) rats, rats subjected to ovariectomy at age 3 weeks, and rats subjected to ovariectomy with a testosterone implant at age 3 weeks.
The combination of removing estrogen early in development and supplementing the ovariectomized females with testosterone revealed strain differences in response of blood pressure. Renin and angiotensinogen messenger RNA levels appear to be regulated coordinately within each strain, although actual levels of messenger RNA differ between the strains.
Similar patterns of responses of renin and angiotensinogen genes to ovariectomy and ovariectomy plus testosterone suggest that regulation of the genes is likely to be similar or coordinate. Differences in regulation of renin-angiotensin system genes between strains may result from epigenetic mechanisms such as genome imprinting of these genes or of another gene that functions as a common regulator of renin and angiotensinogen.
评估具有相同常染色体和X染色体的两种品系雌性大鼠的肾素和血管紧张素原基因表达是否存在差异。雌性SHR/y大鼠具有亲本Wistar-Kyoto大鼠的常染色体和X染色体,且没有自发性高血压大鼠来源的染色体;因此,它们在基因上等同于雌性Wistar-Kyoto大鼠。
由于这些基因受类固醇激素调节,我们研究了去除雌激素(卵巢切除术)和添加雄激素(睾酮植入)对三组雌性SHR/y大鼠以及亲本大鼠品系Wistar-Kyoto大鼠的影响,同时设置了完整(对照)大鼠组、3周龄时接受卵巢切除术的大鼠组以及3周龄时接受卵巢切除术并植入睾酮的大鼠组。
在发育早期去除雌激素并给去卵巢雌性大鼠补充睾酮的联合处理揭示了血压反应的品系差异。肾素和血管紧张素原信使RNA水平在每个品系内似乎受到协同调节,尽管不同品系间信使RNA实际水平有所不同。
肾素和血管紧张素原基因对卵巢切除术及卵巢切除术加睾酮的反应模式相似,这表明这些基因的调节可能相似或协同。品系间肾素-血管紧张素系统基因调节的差异可能源于表观遗传机制,如这些基因或作为肾素和血管紧张素原共同调节因子的另一个基因的基因组印记。