Hospital of Medicine College, Northwest Minzu University, Lanzhou, 730030, China.
School of Karst Science, Guizhou Normal University, Guiyang, 550001, China.
Anticancer Agents Med Chem. 2019;19(14):1719-1727. doi: 10.2174/1871520619666190801094059.
FSH Receptor Binding Inhibitor (FRBI) blocked the binding of FSH to FSHR. Our initial study revealed FRBI reduced the maturation rate, enhanced the apoptosis of sheep Cumulus-Oocyte Complex (COCs). Little is known about whether FRBI modulates ERβ and FSHR levels in the normal uterine and cancerous tissues. The present study aimed to evaluate the FRBI effects on the expressions of Estrogen Receptor-beta (ERβ) and FSH receptor (FSHR) in the uteri.
150 mice were assigned to FRBI+FSH (COM), FSH and control groups (CG). Mice of COM-1, COM-2 and COM-3 groups were simultaneously intramuscularly injected with 500, 750 and 1000 µg FRBI with 10 IU FSH, respectively for five days. Western blotting and qPCR were utilized to determine the expression of ERβ and FSHR.
In comparison with FSH group, uterine lumen and glands of COM groups became narrow. The uterine wall and endometrial epithelium were thinned, and uterine lumen became narrow. Epithelial cells were decreased. Uterine wall thicknesses of COM-1, COM-2 and COM-3 groups were reduced by 6.49%, 14.89% and 15.69% on day 30 as compared with FSH group. Uterine perimetrium thicknesses of COM-1, COM-2 and COM-3 groups were reduced by 16.17%, 17.93% and 19.92% on day 20 in comparison with FSH group. Levels of FSHR mRNAs and proteins of COM-1, COM-2 and COM-3 groups were less than FSH group on days 20 and 30 (P<0.05). ERβ protein of COM-3 group was less than FSH group. Serum estradiol (E2) and FSH concentrations of COM-2 and COM-3 were lower than that of FSH group on day 30.
FRBI could decrease UWT and UPT, also block the uterine development, decline expression levels of ERβ and FSHR protein. Additionally, FRBI reduced the secretion of secretion of FSH and E2. Downregulating expression of FSHR and ERβ may be a potential treatment regimen for cervical cancer patients.
促卵泡激素受体结合抑制剂（FRBI）可阻断 FSH 与 FSHR 的结合。我们的初步研究表明，FRBI 降低了绵羊卵丘-卵母细胞复合物（COCs）的成熟率，并增强了其凋亡。目前尚不清楚 FRBI 是否会调节正常子宫组织和癌组织中 ERβ 和 FSHR 的水平。本研究旨在评估 FRBI 对子宫中雌激素受体-β（ERβ）和 FSH 受体（FSHR）表达的影响。
将 150 只小鼠分为 FRBI+FSH（COM）、FSH 和对照组（CG）。COM-1、COM-2 和 COM-3 组的小鼠分别同时肌肉注射 500、750 和 1000µg FRBI 与 10IU FSH，连续 5 天。采用 Western blot 和 qPCR 法检测 ERβ 和 FSHR 的表达。
与 FSH 组相比，COM 组的子宫腔和腺体变窄。子宫壁和子宫内膜上皮变薄，子宫腔变窄，上皮细胞减少。第 30 天时，COM-1、COM-2 和 COM-3 组的子宫壁厚度分别比 FSH 组减少了 6.49%、14.89%和 15.69%。第 20 天时，COM-1、COM-2 和 COM-3 组的子宫周围厚度比 FSH 组减少了 16.17%、17.93%和 19.92%。第 20 和 30 天时，COM-1、COM-2 和 COM-3 组的 FSHR mRNA 和蛋白水平均低于 FSH 组（P<0.05）。COM-3 组的 ERβ 蛋白水平低于 FSH 组。第 30 天时，COM-2 和 COM-3 组的血清雌二醇（E2）和 FSH 浓度均低于 FSH 组。
FRBI 可降低 UWT 和 UPT，抑制子宫发育，下调 ERβ 和 FSHR 蛋白表达水平。此外，FRBI 降低了 FSH 和 E2 的分泌。下调 FSHR 和 ERβ 的表达可能是宫颈癌患者的一种潜在治疗方案。
