Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.
Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.
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DOI：
10.1095/biolreprod.116.141705
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发表时间：
2016-08
影响因子：
3.6
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
More AS;Mishra JS;Hankins GD;Kumar S
伴有子痫前期和多囊卵巢的孕妇血浆睾酮水平升高；他们的后代在成年后患高血压的风险增加。我们测试了产前睾酮暴露会导致肾素-血管紧张素-醛固酮系统失调的假设，而肾素-血管紧张素-醛固酮系统在水电解质平衡和血压调节中发挥重要作用。雌性大鼠（6月龄）产前暴露于睾酮，检测类固醇基因的肾上腺表达、遥测血压、血容量、Na+和K+水平、血浆醛固酮、血管紧张素II和血管加压素水平，以及血管对血管紧张素II和arg8-血管加压素的反应。在睾酮雌性中，Cyp11b2（醛固酮合成酶）水平下降，而其他肾上腺激素基因没有下降。因此，睾酮女性的血浆醛固酮水平较低。血浆容量、血清和尿液Na+、K+水平在对照组和睾酮组之间无显著差异；然而，产前睾酮暴露显著增加成年女性血浆血管加压素和血管紧张素II水平和动脉压。在睾酮女性中，血管紧张素II的肠系膜动脉收缩反应明显更大，而血管加压素的收缩反应不受影响。睾酮动脉血管紧张素1型受体表达升高，血管紧张素2型受体表达降低。这些结果表明，产前睾酮暴露下调肾上腺Cyp11b2表达，导致血浆醛固酮水平下降。血管紧张素II和血管加压素水平升高以及血管对血管紧张素II的反应性增强可能是维持血浆容量和Na+和K+水平并介导成年睾酮女性高血压的潜在机制。
Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na+ and K+ levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg8-vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na+ and K+ levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na+ and K+ levels and mediate hypertension in adult testosterone females.
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DOI：
10.1186/1477-7827-8-105
发表时间：
2010-08-31
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Cornock R;Langley-Evans SC;Mobasheri A;McMullen S
通讯作者：
McMullen S
影响因子：
3.6
作者：
Chinnathambi, Vijayakumar;More, Amar S.;Sathishkumar, Kunju
通讯作者：
Sathishkumar, Kunju
影响因子：
15.9
作者：
DEFRONZO, RA;COOKE, CR;DAVIS, PJ
通讯作者：
DAVIS, PJ
影响因子：
--
作者：
de Zegher, F;Devlieger, H;Eeckels, R
通讯作者：
Eeckels, R
影响因子：
4
作者：
EDMONDS, CJ
通讯作者：
EDMONDS, CJ