MECHANISM OF ESTROGEN ACTION ON MELANOCYTE FUNCTION

目前的临床、流行病学和实验证据 现有的研究表明，卵巢类固醇直接影响正常 黑素细胞和黑素瘤细胞功能。 其背后的机制 行动仍有待解决。 我们最近提出雌激素 和孕酮改变黑素细胞增殖和黑素生成， 特异性高亲和力受体的作用方式类似于 这些类固醇在其他靶组织中。 本研究的目的是：（1）确定是否存在 正常黑素细胞对雌激素的生物学反应是通过 胞质受体易位到细胞核的方式类似于 黑素瘤细胞。 （这些研究对于确定黑色素瘤是否 细胞反映并放大受体状态和雌激素反应性 正常黑素细胞）;（2）回答是否 雌激素和孕酮对黑素细胞增殖的影响 黑素生成是通过转录因子受体的激活而发生的。 事件或通过对酶功能的直接翻译后作用。 （请参阅 诱导生长和黑素生成的两种标记酶，鸟氨酸 脱羧酶（ODC）和酪氨酸酶。 我们已经开发了一组具有良好特征的人类培养系统， 黑色素瘤细胞以及人和豚鼠黑色素细胞作为探针， 研究雌激素的作用。 我们已经鉴定并量化了细胞质， 人黑色素瘤细胞和黑色素瘤细胞中雌二醇的核受体 组织学上正常的人黑素细胞（痣）。 在实现上述目标方面取得了重大进展。 埃什哈斯 已显示可诱导黑色素瘤细胞中的孕酮受体， 当以生理剂量存在时酪氨酸酶活性。 的影响 雌二醇和孕酮对黑色素瘤细胞生长和黑素生成的影响 受体介导的 （丁）

The clinical, epidemiological, and experimental evidence presently available suggests that ovarian steroids directly influence normal melanocyte and melanoma cell functions. The mechanism(s) underlying their action remains to be resolved. We have recently suggested that estrogen and progesterone alter melanocyte proliferation and melanogenesis via specific, high affinity receptors in a manner similar to the action of these steroids in other target tissues. The objectives of this research are: (1)\\to determine whether the biological response of normal melanocytes to estrogen is mediated via cytosol receptor translocation to the nucleus in a manner similar to melanoma cells. (These studies are critical in determing whether melanoma cells reflect and magnify the receptor status and estrogen responsiveness of normal melanocytes.); and (2)\to answer the question of whether estrogen-\and progesterone-induced alterations of melanocyte proliferation and melanogenesis take place via receptor activation of transcriptional events or by a direct post-translational effect on enzyme function. (The induction of two marker enzymes for growth and melanogenesis, ornithine decarboxylase (ODC), and tyrosinase, respectively, will be followed.) We have developed a panel of well-characterized culture systems of human melanoma cells as well as human and guinea pig melanocytes as probes to study estrogen's action. We have identified and quantified cytosol and nuclear receptors for estradiol in human melanoma cells and from histologically normal human melanocytes (nevi). Significant progress has been made on the above objective. Estradiol has been shown to induce progesterone receptor in melanoma cells and increase tyrosinase activity when present in physiologic doses. The effects of estradiol and progesterone on melanoma cell growth and melanogenesis 0ppear receptor mediated. (D)