Keoxifene (LY 156758) inhibits follicle-stimulating hormone induced differentiation of cultured rat granulosa cells.
Keoxifene (LY 156758) inhibits follicle-stimulating hormone induced differentiation of cultured rat granulosa cells.
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Keoxifene (LY 156758) 抑制促卵泡激素诱导的培养大鼠颗粒细胞的分化。
DOI：
10.1016/0024-3205(87)90572-8
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发表时间：
1987
期刊：
影响因子：
6.1
通讯作者：
Hsueh,AJ
中科院分区：
文献类型：
--
作者：
Kessel,B;Hsueh,AJ
采用原代培养的大鼠颗粒细胞，观察了苯并噻吩类抗雌激素药物可昔昔芬(LY-156758)对颗粒细胞分化的直接影响。可昔芬对促性腺激素刺激的芳香酶活性呈双相抑制作用，低浓度(10−8 M)增强，高浓度(10−6 M)抑制，IC50为5×10−8 M，呈剂量依赖性抑制促黄体生成素受体，IC50为5×10−7 M，提示可昔芬在卵巢水平具有直接药理作用。与早先报道的三苯乙基抗雌激素在卵巢水平的雌激素作用不同，苯并硫醚衍生的抗雌激素可能在临床上更适用于雌激素依赖性恶性肿瘤的治疗。
The direct effects of keoxifene (LY 156758), a benzothiphenederived antiestrogen, on granulosa cell differentiation were examined in vitro using primary cultures of rat granulosa cells. The effect of keoxifene on FSH-stimulated aromatase activity was biphasic in pattern, enhancing at lower concentrations (up to 10− 8 M), and inhibiting at higher concentrations (> 10− 6 M. Keoxifene inhibited FSH-stimulated progestin production in a dose-dependent fashion with an IC 50 of 5× 10− 8 M. FSH-induced LH receptors were also inhibited by keoxifene with an IC 50 of 5× 10− 7 M. These findings suggest that keoxifene has direct pharmacologic actions at the ovarian level. In contrast to the earlier reported estrogenic actions of triphenylethylene antiestrogens at the ovarian level, the benzothiphene-derived antiestrogens may be clinically more useful in the management of estrogen-dependent malignancies.