卵巢颗粒细胞中胰岛素和雄激素对芳香化酶和5α-还原酶1影响的研究

目的研究卵巢颗粒细胞中胰岛素对睾酮激素转化过程的影响。方法选用人卵巢颗粒细胞瘤样细胞系(KGN)作为研究对象。应用RT-PCR分析KGN细胞在梯度睾酮(1.25、2.5、5、10、20ng/ml)及胰岛素(1、10、100ng/ml)处理4h后CYP19a1和5RD5A1mRNA水平;Western-blot检测高浓度睾酮(10、20ng/ml)及梯度胰岛素处理KGN细胞24h后芳香化酶和5α-还原酶1蛋白水平;同步收集上清,应用放射性免疫法及酶联免疫法检测培养液上清睾酮、雌二醇及双氢睾酮的浓度。结果胰岛素剂量依赖性地上调CYP19a1的表达和活性,增加睾酮向雌二醇的转化;同时抑制5RD5A1的表达和活性,抑制睾酮向双氢睾酮的转化;转化比例改变但消耗水平不变,导致睾酮的异常累积。结论高雄激素环境下,胰岛素可通过影响睾酮转化酶促使睾酮转化异常。本实验为高胰岛素及高雄激素水平在卵巢微环境相互作用加剧PCOS病程提出了可能的机制。     

芳香化酶抑制剂致骨质疏松研究进展

乳腺癌患者服用芳香化酶抑制剂(AI)使得卵巢功能缺失导致体内雌激素水平下降,从而加速骨代谢发生骨质疏松.在临床中应给予重视并根据具体情况选择适当防治手段.推荐使用钙剂+维生素D、双膦酸盐、选择性雌激素受体调节剂、中药等药物治疗,减少骨质疏松的发病率.     

乳腺癌靶向治疗药物研究进展

乳腺癌是女性最常见的恶性肿瘤，发病率和死亡率均居女性癌症首位。在科学家探索癌症治疗的各种策略中，靶向治疗特异性强，效果显著，基本上不损伤正常组织，因此是肿瘤治疗中最有前景的方案。靶向治疗应用于乳腺癌也正是目前国内外研究的热点。现主要从抗体药物、小分子药物和芳香化酶抑制剂三个方面综述近年来在乳腺癌治疗药物的研究进展。     

Age-related neurodegenerative changes in the central nervous system of estrogen-deficient follitropin receptor knockout mice

Age-related neurodegenerative conditions are characterized by neuronal death and degeneration that lead to a progressive functional decline. Among the factors influencing degenerative processes during aging are altered levels of neurotrophic ovarian steroid 17beta-estradiol (E2). The follitropin receptor knockout (FORKO) female mouse displays hormonal imbalance characterized by very low levels of circulating E2 and high levels of testosterone. FORKO mice (24 days and 20 months) were used to investigate structural and functional changes in the central nervous system. We now show that the lifelong depletion of the sex hormone E2 in female FORKO mice correlates with abnormal behavior associated with defined alterations in brain morphology early in life, especially in aged animals. Immunohistochemical studies showed significant increases in the size and number of immunoreactive glial fibrillary acidic protein glial cells found in several brain regions (cortex and hippocampus) and a dramatic decline in estrogen receptors alpha and beta in the amygdala of FORKO females. These changes were associated with increased signs of anxiety in these animals. In the present study, we provide evidence that the chronic depletion of sex hormone E2 from early development leads to neural impairments in adult and aged FORKO mice that are associated with hypertrophy of glial cells, cell loss in distinct brain regions, and abnormal behavior. We suggest that the hormonal imbalance found in the female FORKO mouse provides an experimental paradigm for the study of morphological correlates of the behavioral changes that often accompany menopause in women.     

In situ production of estrogens in human breast carcinoma

Recent studies have demonstrated that biologically active estrogens are locally produced from circulating inactive steroids in the estrogen-dependent breast carcinoma. The in situ production of estrogens in the breast carcinoma is considered to play an important role in the proliferation of breast cancer cells, especially in the postmenopausal women. Therefore, the total blockade of this pathway may inhibit estrogenic actions in breast cancer tissues and lead to an improvement in the prognosis in these patients. In this review, we describe the recent studies concerning the expression of enzymes related to intratumoral estrogen production, including aromatase, 17beta-hydroxysteroid dehydrogenase, steroid sulfatase, and estrogen sulfotransferase in human breast carcinoma tissues, and discuss the biological significance of local production of estrogens in human breast cancer.     

针刺对去卵巢大鼠脑内芳香化酶基因表达的影响

本研究旨在探讨雌激素对大鼠脑内芳香化酶（Atom）基因表达的影响和针刺“人中”、“内关”、“三阴交”穴对去卵巢大鼠脑内芳香化酶（Amm）表达的调整作用。实验选用成年4—5个月的SD雌性大鼠，将动物分为假手术组（Sham）、去卵巢组（Ovx）和去卵巢针刺组（Ovx＋Ac），3组动物都进行捆绑。用放射免疫分析方法测定血清中雌二醇、睾酮的含量，通过海马中心组织块的琼脂包被静止培养法转化睾酮，然后用放射免疫法测定雌二醇的量来计算组织块的Aran活性，使用原住杂交和免疫组织化学技术来观察海马AmmmRNA和蛋白的阳性神经元表达，然后使用计算机图像分析系统进行统计分析。实验结果显示：去卵巢大鼠体内雌二醇和睾酮的量明显降低，海马AmmmRNA和蛋白的阳性表达产物的平均面积与灰度值均明显减少，与假手术组相比均有显著性差异，脑内海马中心组织块的Amm活性稍微降低，与假手术组相比较不存在显著性差异；去卵巢针刺组与去卵巢组相比，血清雌二醇水平明显升高，海马AmmmRNA和蛋白的阳性表达产物的平均面积与灰度值均明显升高，血清睾酮水平出现降低，海马组织块的Atom活性出现升高，但没有达到显著性水平。以上结果表明：脑内Amm基因表达与血中雌激素水平密切相关，去卵巢大鼠针刺后脑部Arom基因表达量明显升高，使脑局部雌激素水平升高，对于预防及治疗老年脑部疾病有很好的作用。     

第三代芳香化酶抑制剂临床应用的常见不良反应

芳香化酶抑制剂在解救和辅助治疗乳腺癌方面，均显示出不逊于三苯氧胺的临床疗效．该类药物毒性反应成为人们关注的主要问题。近期资料显示芳香化酶抑制剂对血管、子宫的毒副作用明显少于三苯氧胺，而对血脂、骨丢失的影响较三苯氧胺明显，但该类药物的治疗相关毒性多为轻中度．均可很好处理。由于芳香化酶抑制剂应用时间尚短．其远期毒性还需进一步临床评价。     

A comparison of two months pretreatment with GnRH agonists with or without an aromatase inhibitor in women with ultrasound-diagnosed ovarian endometriomas undergoing IVF

Research question

Does the addition of an aromatase inhibitor improve IVF outcomes in women with endometriomas when pretreating them with gonadotrophin-releasing hormone agonists?

Effects of brain testosterone implants on appetitive and consummatory components of male sexual behavior in Japanese quail

Aromatization of testosterone (T) into an estrogen is necessary for the activation of consummatory and appetitive sexual behavior in male Japanese quail. T action within the medial preoptic nucleus (POM) is necessary and sufficient to activate consummatory behavior, and some evidence suggests that POM might be involved in the control of appetitive behavior, but other brain regions, such as the bed nucleus of the stria terminalis (BST), an area that contains a dense population of aromatase-immunoreactive neurons, are also likely to be involved. This study was performed to assess the effects of stereotaxic T implants targeting either the POM or the BST on the activation of both components of sexual behavior in castrated male quail. Appetitive sexual behavior was measured by an acquired social proximity response in which a male will approach a window providing visual access to a female after the window has been repeatedly paired with physical access to a female and the possibility to freely interact with her. Rhythmic cloacal sphincter movements that are produced by the male when given visual access to a female were used as another measure of appetitive sexual behavior that does not appear to depend on sexual learning. The experiments confirmed that copulation is necessary for males to develop the social proximity response that is used to measure the appetitive sexual behavior. T implants in the POM activated both components of sexual behavior, suggesting that these components cannot be completely dissociated. In contrast, T implants located within the BST did not affect either component, but because implants in the BST did not activate copulatory behavior, these results do not preclude a role for BST in the expression of a previously acquired appetitive sexual behavior.     

The evolving role of endocrine therapy for early stage breast cancer

Conclusions  With the completion of these clinical trials evaluating the integration of AIs in the adjuvant treatment of breast cancer, there are several questions that remain unanswered: (1) What constitutes the optimal endocrine therapy; (2) what is the optimal duration of therapy; (3) what is the optimal sequencing of endocrine agents? It has become obvious from these trials that five years of tamoxifen therapy alone is not optimal adjuvant treatment; the addition of an AI at some point during the course of therapy should be recommended. However, whether the AI should be given as initial treatment or sequenced with tamoxifen remains to be defined. An updated technology assessment developed by the American Society of Clinical Oncology (ASCO) was made available in early 200552). The ASCO panel recommends the following general guidelines for use of aromatase inhibitors: