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氟他胺可增加去势雄性但不增加去势雌性 Wistar 大鼠的醛固酮水平。

Flutamide increases aldosterone levels in gonadectomized male but not female Wistar rats.

机构信息

Clinical Endocrinology, Charité Campus Mitte, Berlin, Germany.

出版信息

Am J Hypertens. 2012 Jun;25(6):697-703. doi: 10.1038/ajh.2012.21. Epub 2012 Mar 8.

DOI:10.1038/ajh.2012.21
PMID:22402471
Abstract

BACKGROUND

Sex-specific differences in blood pressure (BP) suggest an important modulating role of testosterone in the kidney. However, little is known about the interaction between androgens and the mineralocorticoid aldosterone. Our objective was to determine the effects of testosterone in gonadectomized male and female rats on a low-salt diet, and to determine the effect of androgen receptor (AR) blockade by flutamide on BP and on aldosterone levels.

METHODS

Normotensive male and female Wistar rats were gonadectomized and put on a low-salt diet. They were treated for 16 days with testosterone or placebo. In addition, the animals received the AR antagonist flutamide or placebo, respectively. BP was measured by tail-cuff method, 24-h urine samples were collected in metabolic cages and blood was collected for hormonal measurements.

RESULTS

Testosterone increased BP in males and females, and this effect could be blocked by flutamide. Flutamide treatment itself significantly increased aldosterone levels in male but not in female rats. These elevated aldosterone levels could be lowered by testosterone treatment during AR blockade. Accordingly to aldosterone levels, flutamide increased in males the serum sodium/potassium to urinary sodium/potassium ratio, an in vivo indicator of renal aldosterone action.

CONCLUSIONS

Testosterone regulates BP in male and female gonadectomized rats via the AR. Flutamide by itself exerts influence over aldosterone in the absence of gonadal steroid replacement suggesting AR involvement in renal sodium handling. These flutamide effects were sex-specific and not seen in female rats.

摘要

背景

血压(BP)存在性别差异,提示睾丸酮在肾脏中具有重要的调节作用。然而,人们对雄激素和盐皮质激素醛固酮之间的相互作用知之甚少。我们的目的是确定去势雄性和雌性大鼠在低盐饮食下睾丸酮的作用,并确定雄激素受体(AR)阻断剂氟他胺对 BP 和醛固酮水平的影响。

方法

正常血压的雄性和雌性 Wistar 大鼠去势并给予低盐饮食。它们分别用睾丸酮或安慰剂治疗 16 天。此外,动物分别接受 AR 拮抗剂氟他胺或安慰剂治疗。通过尾套法测量 BP,在代谢笼中收集 24 小时尿液样本,并采集血液进行激素测量。

结果

睾丸酮增加了雄性和雌性大鼠的 BP,这种作用可以被氟他胺阻断。氟他胺治疗本身显著增加了雄性大鼠而不是雌性大鼠的醛固酮水平。在 AR 阻断期间用睾丸酮治疗可以降低这些升高的醛固酮水平。相应地,根据醛固酮水平,氟他胺增加了雄性大鼠血清钠/钾与尿钠/钾比值,这是体内反映肾脏醛固酮作用的指标。

结论

睾丸酮通过 AR 调节去势雄性和雌性大鼠的 BP。氟他胺本身在没有性腺类固醇替代的情况下对醛固酮产生影响,提示 AR 参与肾脏钠处理。这些氟他胺的作用具有性别特异性,在雌性大鼠中未观察到。

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