雌激素导致血浆钾浓度存在性别差异：一种调节肾上腺血管紧张素受体的机制。

Estrogens contribute to a sex difference in plasma potassium concentration: a mechanism for regulation of adrenal angiotensin receptors.

作者信息

Zheng Wei, Shi Min, You Sung-Eun, Ji Hong, Roesch Darren M

机构信息

Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC 20057, USA.

出版信息

Gend Med. 2006 Mar;3(1):43-53. doi: 10.1016/s1550-8579(06)80193-2.

DOI:10.1016/s1550-8579(06)80193-2

PMID:16638600

Abstract

BACKGROUND

The adrenal mineralocorticoid aldosterone promotes sodium (Na(+)) reabsorption and potassium (K(+)) loss from the kidney. Female sex steroids such as estrogen and progesterone are known modulators of the renin-angiotensin-aldosterone system.

OBJECTIVE

We conducted studies to determine if there is a sex difference in plasma Na(+) concentration ([Na(+)]) and plasma K(+) concentration ([K(+)]), and if interactions between female sex steroids and aldosterone contribute to a sex difference in these electrolytes.

METHODS

Plasma [Na(+)] and [K(-)] were determined in weight-matched male and female Sprague-Dawley rats using an ion-selective electrode system. To assess the sensitivity of males and females to aldosterone, the mineralocorticoid was infused chronically by osmotic minipump. The role of female sex steroids in the regulation of plasma electrolyte concentrations was determined in bilaterally ovariectomized (OVX) female rats treated daily with SC injections of progesterone, 17beta-estradiol (E(2)), or selective estrogen receptor (ER) modulators. The role of plasma [K(+)] in the regulation of adrenal angiotensin II type 1 receptor (AT(1)R) expression was determined by manipulating plasma [K(+)] by varying dietary K(-). Adrenal AT(1)R expression was assessed using a radioligand binding assay.

RESULTS

Plasma [Na(-)] was not different between male and female rats, but plasma [K(-)] was reduced in females compared with males (P = 0.003). In aldosterone-infused female rats, plasma [Na(+)] was increased and plasma [K(+)] was reduced further than in male rats infused with aldosterone (both, P = 0.001). In OVX female rats, progesterone reduced plasma [Na(+)] (P = 0.04) but had no effect on plasma [K(+)]. In contrast, E(2) increased plasma [Na(+)] (P = 0.01) and reduced plasma [K(+)] (P = 0.001). Dietary K supplementation in E(2)-treated rats returned plasma [K(+)] and adrenal AT(1)R binding to levels observed in control rats. Both an ERa and ERP agonist decreased plasma [K(+)] and decreased adrenal AT(1)R binding (both, P < 0.01).

CONCLUSIONS

In these studies, plasma [K(+)] was reduced in female Sprague-Dawley rats compared with males. The effects of aldosterone on plasma electrolytes were enhanced in females compared with males. E(2) treatment reduced plasma [K(+)] and adrenal AT(1)R binding in OVX rats, and the decrease in plasma [K(+)] contributed to the decrease in adrenal AT(1)R binding. Both ERalpha and ERbeta contributed to the estrogen-induced decrease in plasma [K(+)] and adrenal AT(1)R binding.

摘要

背景

肾上腺盐皮质激素醛固酮可促进肾脏对钠（Na⁺）的重吸收和钾（K⁺）的排泄。雌激素和孕激素等女性性激素是肾素 - 血管紧张素 - 醛固酮系统的已知调节因子。

目的

我们进行了多项研究，以确定血浆钠浓度（[Na⁺]）和血浆钾浓度（[K⁺]）是否存在性别差异，以及女性性激素与醛固酮之间的相互作用是否导致这些电解质的性别差异。

方法

使用离子选择性电极系统测定体重匹配的雄性和雌性Sprague - Dawley大鼠的血浆[Na⁺]和[K⁻]。为评估雄性和雌性对醛固酮的敏感性，通过渗透微型泵长期输注盐皮质激素。在双侧卵巢切除（OVX）的雌性大鼠中，每日皮下注射孕激素、17β - 雌二醇（E₂）或选择性雌激素受体（ER）调节剂，以确定女性性激素在调节血浆电解质浓度中的作用。通过改变饮食中的钾含量来调节血浆[K⁺]，从而确定血浆[K⁺]在调节肾上腺血管紧张素II 1型受体（AT₁R）表达中的作用。使用放射性配体结合测定法评估肾上腺AT₁R表达。

结果

雄性和雌性大鼠的血浆[Na⁻]无差异，但雌性大鼠的血浆[K⁻]低于雄性大鼠（P = 0.003）。与输注醛固酮的雄性大鼠相比，输注醛固酮的雌性大鼠血浆[Na⁺]升高，血浆[K⁺]进一步降低（两者均P = 0.001）。在OVX雌性大鼠中，孕激素降低了血浆[Na⁺]（P = 0.04），但对血浆[K⁺]无影响。相反，E₂增加了血浆[Na⁺]（P = 0.01）并降低了血浆[K⁺]（P = 0.001）。在E₂处理的大鼠中补充饮食钾后，血浆[K⁺]和肾上腺AT₁R结合恢复到对照大鼠的水平。ERα和ERβ激动剂均降低了血浆[K⁺]并降低了肾上腺AT₁R结合（两者均P < 0.01）。

结论

在这些研究中，雌性Sprague - Dawley大鼠的血浆[K⁺]低于雄性大鼠。与雄性相比，醛固酮对雌性血浆电解质的影响增强。E₂处理降低了OVX大鼠的血浆[K⁺]和肾上腺AT₁R结合，血浆[K⁺]的降低导致肾上腺AT₁R结合的减少。ERα和ERβ均促成了雌激素诱导的血浆[K⁺]和肾上腺AT₁R结合的降低。