Hypothalamic neuroendocrine functions in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electro-acupuncture.

Hypothalamic neuroendocrine functions in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electro-acupuncture.
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DOI:
10.1371/journal.pone.0006638
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发表时间:
2009-08-14
期刊:
影响因子:
3.7
通讯作者:
Stener-Victorin E
Stener-Victorin E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Feng Y;Johansson J;Shao R;Mannerås L;Fernandez-Rodriguez J;Billig H;Stener-Victorin E

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成年雌性大鼠从青春期前开始持续暴露于雄激素,具有多囊卵巢综合征(PCOS)的生殖代谢特征。我们研究了这种暴露是否会对发情周期以及下丘脑中促性腺激素释放激素(GnRH)、GnRH受体和促肾上腺皮质激素释放激素(CRH)的表达和分布产生不利影响,以及这些影响是否由雄激素受体(AR)介导。我们还评估了低频电针(EA)对这些变量的影响。在21日龄时,将大鼠随机分为3组(对照组、PCOS组和PCOS EA组; n = 12/组),并皮下植入含有溶媒或5α-二氢甾体酮(DHT)的90天连续释放微丸。  从70日龄开始,PCOS EA大鼠接受2-Hz EA(诱发肌肉抽搐),每周5次,持续4-5周。免疫组化和western blot检测下丘脑蛋白表达。DHT处理的大鼠是无周期的,但对照组有规律的发情周期。在PCOS大鼠,下丘脑内侧视前区AR蛋白的表达和AR-和GnRH-免疫反应细胞的数量增加,但CRH不受影响,然而,GnRH受体的表达下降,在垂体和下丘脑。低频电针可在1周内恢复动情周期,并降低下丘脑GnRH和AR表达水平。电针不影响GnRH受体和CRH的表达。有趣的是,核AR与下丘脑中的GnRH共定位。因此,DHT诱导的PCOS大鼠的发情周期被破坏,下丘脑表达GnRH的细胞数量增加,这很可能是由AR激活介导的。重复低频电针使动情周期正常化,并恢复GnRH和AR蛋白表达。这些结果可能有助于解释低频EA对PCOS女性的有益神经内分泌作用。
Adult female rats continuously exposed to androgens from prepuberty have reproductive and metabolic features of polycystic ovary syndrome (PCOS). We investigated whether such exposure adversely affects estrous cyclicity and the expression and distribution of gonadotropin-releasing hormone (GnRH), GnRH receptors, and corticotrophin-releasing hormone (CRH) in the hypothalamus and whether the effects are mediated by the androgen receptor (AR). We also assessed the effect of low-frequency electro-acupuncture (EA) on those variables. At 21 days of age, rats were randomly divided into three groups (control, PCOS, and PCOS EA; n = 12/group) and implanted subcutaneously with 90-day continuous-release pellets containing vehicle or 5α-dihydrostestosterone (DHT). From age 70 days, PCOS EA rats received 2-Hz EA (evoking muscle twitches) five times/week for 4–5 weeks. Hypothalamic protein expression was measured by immunohistochemistry and western blot. DHT-treated rats were acyclic, but controls had regular estrous cycles. In PCOS rats, hypothalamic medial preoptic AR protein expression and the number of AR- and GnRH-immunoreactive cells were increased, but CRH was not affected; however, GnRH receptor expression was decreased in both the pituitary and hypothalamus. Low-frequency EA restored estrous cyclicity within 1 week and reduced the elevated hypothalamic GnRH and AR expression levels. EA did not affect GnRH receptor or CRH expression. Interestingly, nuclear AR co-localized with GnRH in the hypothalamus. Thus, rats with DHT-induced PCOS have disrupted estrous cyclicity and an increased number of hypothalamic cells expressing GnRH, most likely mediated by AR activation. Repeated low-frequency EA normalized estrous cyclicity and restored GnRH and AR protein expression. These results may help explain the beneficial neuroendocrine effects of low-frequency EA in women with PCOS.
DOI: 10.1159/000126810
发表时间: 1995-01-01
期刊: NEUROENDOCRINOLOGY
影响因子: 4.1
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影响因子: 6.7
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发表时间: 2002-11-01
影响因子: --
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