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Studies on the effects of estrogen fatty acid esters on mammary cell growth and carcinogenesis in female rats.

机译：雌激素脂肪酸酯对雌性大鼠乳腺细胞生长和致癌作用的研究。

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摘要

The naturally occurring estrogen fatty acid esters are a unique group of estrogen derivatives that are formed from the enzymatic esterification of E2 (at the C-17 position) using various fatty acyl-CoAs as cofactors. These lipophilic estrogen derivatives cannot bind to the estrogen receptor, rather their hormonal activity results from the slow enzymatic release of the parent hormone. Because of their high lipophilicity, estrogen fatty acid esters are found at higher concentrations in the fat than in the blood. Therefore, it is possible that the mammary adipocytes may serve as a storage site for the lipoidal estrogen fatty acid esters.; It was hypothesized that the estrogen fatty acid esters are a group of mammary selective hormones that are especially important for stimulating cell growth and inducing tumor formation in the fat-rich mammary tissues when compared to the uterus and pituitary. Data showed that chronic administration of 0.5 or 5 nmol/day of E2-17β-stearate (a representative estrogen fatty acid ester) to ovariectomized Sprague-Dawley rats for 10 or 23 days had a markedly stronger stimulatory effect on mammary glandular cell growth than did E2 at equimolar doses, while E2 showed a preferential growth stimulatory effect in the uterus of these animals.{09}In addition, it was shown that the chronic administration of an E2-17β-fatty acid ester preparation to ACI rats preferentially induced the development of mammary tumors while chronic administration of E2 resulted in the preferential formation of pituitary tumors.{09}This is the first report demonstrating that chronic administration of an estrogen fatty acid ester selectively induces the development of mammary tumors in this animal model.; It would be of great interest to advance our knowledge on the biological effects of other naturally occurring estrogen-fatty acid ester derivatives. However, very few estrogen fatty acid esters are sold commercially. Therefore, a facile method for the chemical synthesis of large amounts of 4-hydroxyestradiol-17β-stearate, a representative fatty acid ester of the strongly procarcinogenic estrogen metabolite 4-hydroxyestradiol, was developed. The availability of large amounts of chemically synthesized 4-hydroxyestradiol-17β-fatty acid esters makes it possible for future studies to characterize their hormonal and carcinogenic potency in animals and humans.
机译：天然存在的雌激素脂肪酸酯是独特的一组雌激素衍生物，是由E 2 （在C-17位置）通过酶促酯化反应而形成的，使用各种脂肪酰基辅酶A作为辅因子。这些亲脂性的雌激素衍生物不能与雌激素受体结合，相反，它们的激素活性是由母体激素的缓慢酶促释放引起的。由于它们的亲脂性高，在脂肪中发现的雌激素脂肪酸酯的浓度比在血液中的浓度高。因此，乳腺脂肪细胞有可能充当脂质雌激素脂肪酸酯的储存位点。据推测，雌激素脂肪酸酯是一组乳腺选择性激素，与子宫和垂体相比，它们对于刺激富含脂肪的乳腺组织中的细胞生长和诱导肿瘤形成特别重要。数据显示，对卵巢切除的Sprague-Dawley大鼠长期给予0.5或5 nmol /天的E 2 -17β-硬脂酸酯（代表性的雌激素脂肪酸酯）刺激10或23天，刺激性明显增强等摩尔剂量的E 2 对乳腺细胞生长的影响，而E 2 对这些动物的子宫表现出优先的生长刺激作用。{09}此外，结果表明，长期给ACI大鼠长期服用E 2 -17β-脂肪酸酯制剂会优先诱导乳腺肿瘤的发展，而长期给予E 2 会导致乳腺肿瘤的发生。 {09}这是第一个报道，证明长期服用雌激素脂肪酸酯在该动物模型中选择性诱导了乳腺肿瘤的发展。提高我们对其他天然存在的雌激素-脂肪酸酯衍生物的生物学效应的认识将是非常有意义的。但是，很少有商业出售的雌激素脂肪酸酯。因此，开发了一种用于化学合成大量4-羟雌二醇-17β-硬脂酸酯的简便方法，所述4-羟雌二醇-17β-硬脂酸酯是强致癌性雌激素代谢物4-羟雌二醇的代表性脂肪酸酯。大量化学合成的4-羟基雌二醇-17β-脂肪酸酯的可用性使将来的研究有可能表征它们在动物和人类中的激素和致癌作用。

著录项

  • 作者

    Mills, Laura Hook.;

  • 作者单位

    University of South Carolina.;

  • 授予单位 University of South Carolina.;
  • 学科 Health Sciences Pharmacology.; Chemistry Biochemistry.; Biology Cell.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 161 p.
  • 总页数 161
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;生物化学;细胞生物学;
  • 关键词

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