Expression of gonadotropin receptor and growth responses to key reproductive hormones in normal and malignant human ovarian surface epithelial cells.
Expression of gonadotropin receptor and growth responses to key reproductive hormones in normal and malignant human ovarian surface epithelial cells.
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发表时间：
2001-09
期刊：
影响因子：
11.2
通讯作者：
Viqar Syed;Gregory Ulinski;S. C. Mok;Gary K. Yiu;Shuk Meia Ho
中科院分区：
文献类型：
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作者：
Viqar Syed;Gregory Ulinski;S. C. Mok;Gary K. Yiu;Shuk Meia Ho
流行病学数据表明，生殖激素可能是卵巢癌（OCa）发生的危险因素。虽然垂体和性激素已被报道调节OCa细胞的生长，没有关于它们是否以及如何影响正常卵巢表面上皮（OSE）细胞增殖的信息。为了填补这一数据空白，本研究比较了原代培养的人OSE（HOSE）细胞与永生化的非致瘤性HOSE细胞和OCa细胞系中观察到的促性腺激素和性类固醇的细胞生长反应。恶性和正常细胞系/培养物对促黄体激素和促卵泡激素以及17 β-雌二醇和雌酮的刺激作用反应同样良好，尽管后者雌激素对雌激素受体的亲和力比前者雌激素低得多。在正常HOSE细胞培养物/系中，发现5 α-二氢睾酮在刺激细胞生长方面比睾酮更有效，但在OCa细胞系中，5 α-二氢睾酮和睾酮同样有效。一种OCa细胞系OVCA 433被发现对雄激素刺激无反应。一般来说，正常HOSE细胞的原代培养物表现出最大的细胞刺激的生长反应（>10倍增强），其次是永生化HOSE细胞系（4-5倍增强）和OCa细胞系（2-4倍增强）。有趣的是，低浓度（10（-11）至10（-10）M）的孕酮（P4）对HOSE和OCa细胞生长有刺激作用，但在高剂量（10（-8）至10（-6）M）时，P4表现出明显的抑制作用。在所有情况下，用激素及其特异性拮抗剂共同处理细胞培养物/细胞系阻断了激素的作用，证实了激素作用的特异性。总之，这些数据支持这一假设，即生殖状态与促性腺激素，雌激素和/或雄激素水平的上升，促进细胞增殖的正常OSE，这有利于肿瘤转化。相反，那些参与高水平循环P4的状态，如妊娠期间所见，诱导OSE细胞丢失并提供对卵巢癌发生的保护。
Epidemiological data have implicated reproductive hormones as probable risk factors for ovarian cancer (OCa) development. Although pituitary and sex hormones have been reported to regulate OCa cell growth, no information is available regarding whether and how they influence normal ovarian surface epithelial (OSE) cell proliferation. To fill this data gap, this study has compared cell growth responses to gonadotropins and sex steroids in primary cultures of human OSE (HOSE) cells with those observed in immortalized, nontumorigenic HOSE cells and in OCa cell lines. Both malignant and normal cell lines/cultures responded equally well to the stimulatory actions of luteinizing hormone and follicle-stimulating hormone and to 17beta-estradiol and estrone, although the latter estrogen has a much lower affinity for estrogen receptor than does the former estrogen. In normal HOSE cell cultures/lines, 5alpha-dihydrotestosterone was found to be more effective than testosterone in stimulating cell growth, but in OCa cell lines, 5alpha-dihydrotestosterone and testosterone are equally potent. One OCa cell line, OVCA 433, was found to be nonresponsive to androgen stimulation. In general, primary cultures of normal HOSE cells exhibited the greatest hormone-stimulated growth responses (>10-fold enhancement), followed by immortalized HOSE cell lines (4-5-fold enhancement) and by OCa cell lines (2-4-fold enhancement). Interestingly, progesterone (P4), at low concentrations (10(-11) to 10(-10) M), was stimulatory to HOSE and OCa cell growth, but at high doses (10(-8) to 10(-6) M), P4 exerted marked inhibitory effects. In all cases, cotreatment of a cell culture/line with a hormone and its specific antagonist blocked the effect of the hormone, confirming specificity of the hormonal action. Taken together, these data support the hypothesis that reproductive states associated with rising levels of gonadotropins, estrogen, and/or androgen promote cell proliferation in the normal OSE, which favors neoplastic transformation. Conversely, those states attended by high levels of circulating P4, such as that seen during pregnancy, induce OSE cell loss and offer protection against ovarian carcinogenesis.