Division of Endocrinology, Central Drug Research Institute, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, India.
Fertil Steril. 2011 Mar 15;95(4):1322-7. doi: 10.1016/j.fertnstert.2010.06.066. Epub 2010 Aug 1.
To investigate the anti-implantation effect and hormonal profile of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in rats.
In vivo assays for anti-implantation activity were performed in pregnant rats. Assays for estrogenicity/antiesrogenicity were performed in immature ovariectomized female rats. In vitro competitive binding of K-1 to human recombinant ERα, transient transfection assay using ERE-luciferase reporter, and alkaline phosphatase (ALP) activity as a measure of estrogenicity and/antiestrogenicity in human endometrial carcinoma cells were performed.
Research laboratory.
ANIMAL(S): Adult female rats for anti-implantation activity, immature ovariectomized female rats, and immature castrated/intact male rats.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Number of implantations, uterine growth, luciferase reporter activity, ER binding affinity, and ALP activity.
RESULT(S): Compound K-1 given orally for 1-7 days post coitum at the dose of 100 μg/kg body weight prevented pregnancy in 100% of rats. K-1 was a potent antiestrogenic, and at 50 μg/kg, it could inhibit the effect of 1 μg E(2) in immature rats. Compound was devoid of uterotrophic, androgenic, or antigonadotropic activity. A high affinity binding to ERα was displayed by K-1, with a relative binding affinity of 5% of E(2). In human endometrial carcinoma cells, K-1 did not induce ERα-mediated transcriptional activation that is measured as luciferase reporter activity. K-1 antagonized the E-induced transcriptional activation significantly. K-1 also antagonized E-induced ALP activity in human endometrial cells.
CONCLUSION(S): K-1 appeared to exert its antifertility action by virtue of its strong antiestrogenic activity.
研究 2-[哌啶乙氧基苯]-3-[4-羟苯基]-2H-苯并（b）色烯（K-1）在大鼠体内的抗着床作用和激素谱。
在怀孕大鼠中进行抗着床活性的体内检测；在未成熟去卵巢雌性大鼠中进行雌激素/抗雌激素活性检测。进行 K-1 与人重组 ERα 的体外竞争结合、使用 ERE-荧光素酶报告基因的瞬时转染测定以及碱性磷酸酶（ALP）活性作为人子宫内膜癌细胞中雌激素和/抗雌激素活性的测定。
研究实验室。
用于抗着床活性的成年雌性大鼠、未成熟去卵巢雌性大鼠和未成熟去势/完整雄性大鼠。
无。
着床数、子宫生长、荧光素酶报告基因活性、ER 结合亲和力和 ALP 活性。
K-1 在交配后 1-7 天每天口服 100μg/kg 体重可阻止 100%的大鼠怀孕。K-1 是一种有效的抗雌激素药物，在 50μg/kg 时，它可以抑制未成熟大鼠中 1μg E（2）的作用。化合物没有子宫营养、雄激素或抗性腺激素活性。K-1 与人 ERα 显示出高亲和力结合，相对结合亲和力为 E（2）的 5%。在人子宫内膜癌细胞中，K-1 不会诱导 ERα 介导的转录激活，该转录激活通过荧光素酶报告基因活性进行测量。K-1 显著拮抗 E 诱导的转录激活。K-1 还拮抗 E 诱导的人子宫内膜细胞中 ALP 活性。
K-1 似乎通过其强大的抗雌激素活性发挥其抗生育作用。
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