Hypertension caused by prenatal testosterone excess in female sheep
Hypertension caused by prenatal testosterone excess in female sheep
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DOI：
10.1152/ajpendo.00668.2006
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发表时间：
2007-06-01
影响因子：
5.1
通讯作者：
Fink, Gregory D.
中科院分区：
文献类型：
--
作者：
King, Andrew J.;Olivier, N. Bari;Fink, Gregory D.
多囊卵巢综合征（PCOS）是导致不孕的主要原因，影响着大约10%的育龄妇女。多囊卵巢综合征的病因和病理生理尚不清楚。多囊卵巢综合征是多方面的，包括生殖异常和代谢综合征的组成部分，如胰岛素抵抗、肥胖、血脂异常和高血压。在产前暴露于过量的睾酮(T)可能使个体易患PCOS表型。本研究的目的是确定高血压和血脂异常是否发生在一个特征良好的多囊卵巢综合征模型中，该模型是由产前用t治疗绵羊产生的，使用无线电遥测法测量清醒、未受干扰的动物24小时内的血压。为了在治疗期间使循环雌二醇水平正常化，对照组（n = 4）和产前T治疗（100 mg丙酸T，每周两次，从胎儿生命的第30天到第90天，n = 4）， 2岁的雌性卵巢切除，用无线电遥测发射机测量，并用植入物夹住早期卵泡期雌激素水平。6天后，24小时的记录周期开始。与对照组相比，产前T治疗的绵羊有高血压，心率有升高的趋势。T处理的羊有高血糖、胰岛素抵抗、高钠血症和高氯血症，总胆固醇和低密度脂蛋白胆固醇都趋于较高。T处理的羊血浆醛固酮和肾上腺素显著降低，而去甲肾上腺素不变。这是首次在绵羊中使用无线电遥测血压记录，表明轻度高血压是一些多囊卵巢综合征妇女的危险因素，也是产前T治疗产生的多囊卵巢综合征绵羊模型的一个特征。
Polycystic ovary syndrome ( PCOS), a leading cause of infertility, affects similar to 10% of women of reproductive age. The etiology and pathophysiology of PCOS are poorly understood. PCOS is multifaceted and includes reproductive abnormalities and components of the metabolic syndrome such as insulin resistance, obesity, dyslipidemia, and hypertension. Exposure to excess testosterone ( T) during the prenatal period may predispose individuals to PCOS phenotype. The goal of this study was to determine whether hypertension and dyslipidemia occur in a well- characterized model of PCOS produced by prenatal treatment of sheep with T. Radiotelemetry was used to measure blood pressure over a 24- h period in conscious, undisturbed animals. To normalize circulating estradiol levels across treatment, control ( n = 4) and prenatal T- treated ( 100 mg T propionate im twice weekly from days 30 to 90 of fetal life, n = 4) 2- yr- old females were ovariectomized, instrumented with a radiotelemetry transmitter, and clamped with early follicular phase levels of estrogen using an implant. Six days later, a 24- h recording period commenced. Prenatal T- treated sheep were hypertensive compared with control sheep, and heart rate tended to be higher. T- treated sheep had hyperglycemia, insulin resistance, hypernatremia, and hyperchloremia, and both total and LDL cholesterol tended to be higher. Plasma aldosterone and epinephrine were significantly lower in T- treated sheep, whereas norepinephrine was unchanged. This first- ever use of radiotelemetric blood pressure recordings in sheep demonstrates that mild hypertension, a risk factor reported in some women with PCOS, is also a feature of the sheep model of PCOS produced by prenatal T treatment.