...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Frontiers in neuroendocrinology >DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology.
【24h】

DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology.

机译：DHEA及其在外周靶组织中转化为雄激素和雌激素的方法：内分泌学。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A new understanding of the endocrinology of menopause is that women, at menopause, are not only lacking estrogens resulting from cessation of ovarian activity but have also been progressively deprived for a few years of androgens and some estrogens originating from adrenal DHEA and androstenedione (4-dione). In fact, serum DHEA decreases by about 60% between the maximal levels seen at 30 years of age to the age of menopause. This decreased secretion of DHEA and DHEA-S by the adrenals is responsible for a parallel decrease in androgen and estrogen formation in peripheral tissues by the steroidogenic enzymes specifically expressed in each cell type in individual target tissues. This new field of endocrinology, called intracrinology, describes the local synthesis of androgens and estrogens made locally in each cell of each peripheral tissue from the adrenal precursors DHEA and 4-dione. These androgens and estrogens exert their action in the same cells where their synthesis takes place and they are released from these target cells only after being inactivated. To further understand the effect of DHEA in women, DHEA has been administered in postmenopausal women for 12 months. Such treatment resulted in increased bone formation and higher bone mineral density accompanied by elevated levels of osteocalcin, a marker of bone formation. Vaginal maturation was stimulated, while no effect was observed on the endometrium. Preclinical studies, on the other hand, have shown that, due to its predominant conversion into androgens, DHEA prevents the development and inhibits the growth of dimethylbenz(a)anthracene-induced mammary carcinoma in the rat, a model of breast cancer. DHEA also inhibits the growth of human breast cancer ZR-75-1 xenografts in nude mice. The inhibitory effect of DHEA on breast cancer is due to an androgenic effect of testosterone and dihydrotestosterone made locally from DHEA. When used as replacement therapy, DHEA is free of the potential risk of breast and uterine cancer, while it stimulates bone formation and vaginal maturation and decreases insulin resistance. The combination of DHEA with a fourth generation SERM, such as EM-652 (SCH 57068), a compound having pure and potent antiestrogenic activity in the mammary gland and endometrium, could provide major benefits for women at menopause (inhibition of bone loss and serum cholesterol levels) with the associated major advantages of preventing breast and uterine cancer. A widely used application of intracrinology is the treatment of prostate cancer where the testicles are blocked by an LHRH agonist while the androgens made locally in the prostate from DHEA are blocked by a pure antiandrogen. Such treatment, called combined androgen blockade, has led to the first demonstration of a prolongation of life in prostate cancer. Copyright 2001 Academic Press.
机译：对更年期内分泌学的新认识是，更年期的妇女不仅缺乏因卵巢活动停止而产生的雌激素，而且在过去的几年中被逐渐剥夺了雄激素和一些源自肾上腺DHEA和雄烯二酮的雌激素（4- dione）。实际上，血清DHEA在30岁至绝经年龄之间的最高水平之间降低了约60％。肾上腺的DHEA和DHEA-S分泌减少是由于在各个靶组织中每种细胞类型中特异性表达的类固醇生成酶导致外周组织中雄激素和雌激素形成的平行减少的原因。内分泌学这个​​新领域称为内分泌学，描述了由肾上腺前体DHEA和4-dione在每个周围组织的每个细胞中局部产生的雄激素和雌激素的局部合成。这些雄激素和雌激素在发生其合成的相同细胞中发挥作用，并且仅在被灭活后才从这些靶细胞中释放出来。为了进一步了解脱氢表雄酮对女性的作用，脱氢表雄酮已在绝经后的女性体内使用了12个月。这种治疗导致增加的骨形成和更高的骨矿物质密度，同时伴随着骨钙蛋白（骨形成的标志物）水平升高。刺激阴道成熟，而对子宫内膜未观察到影响。另一方面，临床前研究表明，由于脱氢表雄酮（DHEA）主要转化为雄激素，因此可阻止这种模型发展并抑制二甲基苯并蒽诱导的大鼠乳腺癌（一种乳腺癌模型）的生长。 DHEA还抑制裸鼠中人乳腺癌ZR-75-1异种移植物的生长。 DHEA对乳腺癌的抑制作用是由于从DHEA局部制备的睾丸激素和二氢睾丸激素的雄激素作用。当用作替代疗法时，DHEA消除了乳腺癌和子宫癌的潜在风险，同时它可以刺激骨骼形成和阴道成熟并降低胰岛素抵抗。 DHEA与第四代SERM（例如EM-652（SCH 57068），一种在乳腺和子宫内膜中具有纯而有效的抗雌激素活性的化合物）的组合可为绝经期妇女提供主要益处（抑制骨质流失和血清胆固醇水平）具有预防乳腺癌和子宫癌的相关主要优势。内分泌学的广泛应用是前列腺癌的治疗，其中睾丸被LHRH激动剂阻断，而从DHEA在前列腺中局部产生的雄激素被纯的抗雄激素阻断。这种称为联合雄激素阻断的治疗方法，首次证明了前列腺癌寿命的延长。版权所有2001，学术出版社。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号