Effect of progestin on the ovarian epithelium of macaques: Cancer prevention through apoptosis?
Effect of progestin on the ovarian epithelium of macaques: Cancer prevention through apoptosis?
复制标题
DOI：
10.1016/s1071-5576(98)00017-3
复制
发表时间：
1998-09-01
期刊：
影响因子：
--
通讯作者：
Hughes, CL
中科院分区：
文献类型：
--
作者：
Rodriguez, GC;Walmer, DK;Hughes, CL
OBJECTIVE: The apoptosis pathway is a vital mechanism in vivo that functions to eradicate genetically damaged cells prone to malignancy. The purpose of this study was to determine whether oral contraceptives, which confer significant protection against subsequent epithelial ovarian cancer, induce apoptosis in the ovarian epithelium.METHODS: Female cynomolgus macaques (N = 75) were randomized to receive a diet for 35 months containing either no hormones, the oral contraceptive Triphasil (Wyeth-Ayerst Laboratories, Philadelphia, PA), the estrogenic component of Triphasil (ethinyl estradiol) alone, or the progestin component of Triphasil (levonorgestrel) alone, each administered in a cyclic fashion. At study termination, the animals underwent ovariectomy and the ovarian epithelium was examined morphologically and immunohistochemically for apoptosis. The percentage of ovarian epithelial cells undergoing apoptosis was measured in each animal and compared between the treatment groups.RESULTS: The median percentage of ovarian epithelial cells undergoing apoptosis by treatment was control (3.8%), ethinyl estradiol (1.8%), Triphasil (14.5%), and levonorgestrel (24.9%). Compared with control and ethinyl estradiol-treated monkeys, a statistically significant increase in the proportion of apoptotic cells was noted in the ovarian epithelium of monkeys treated with the oral contraceptive Triphasil (P less than or equal to .01) or levonorgestrel (P < .001), with a maximal effect (six-fold) seen in the group treated with levonorgestrel alone.CONCLUSION: Oral contraceptive progestin induces apoptosis in the ovarian epithelium. Given the importance of the apoptosis pathway for cancer prevention, an effective chemopreventive strategy may be possible using progestins or other agents that selectively induce apoptosis in the ovarian epithelium to prevent the development of ovarian cancer. Copyright (C) 1998 by the Society for Gynecologic Investigation.
