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MECHANISM OF ESTROGEN ACTION ON MELANOCYTE FUNCTION

雌激素对黑素细胞功能的作用机制

基本信息

批准号：
3169456
负责人：
CRAIG W BEATTIE
金额：
$ 6.64万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 1987-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3169456
关键词：
estradiol genetic transcription genetic translation hormone regulation /control mechanism melanocyte neoplasm /cancer genetics neoplastic cell ornithine decarboxylase steroid hormone tyrosine

项目摘要

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)

目前的临床、流行病学和实验证据现有研究表明卵巢类固醇直接影响正常黑色素细胞和黑色素瘤细胞的功能。其背后的机制行动仍有待解决。我们最近建议雌激素黄体酮通过改变黑素细胞增殖和黑素生成特异性的高亲和力受体，其作用方式类似于这些类固醇存在于其他靶组织中。本研究的目的是： (1) 确定是否正常黑素细胞对雌激素的生物反应是通过胞质受体以类似的方式易位至细胞核黑色素瘤细胞。（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正常黑素细胞。）；和 (2)\ 来回答是否雌激素\和孕激素诱导的黑素细胞增殖改变黑素生成是通过转录受体激活而发生的事件或对酶功能的直接翻译后效应。（这诱导生长和黑色素生成的两种标记酶——鸟氨酸接下来将分别是脱羧酶（ODC）和酪氨酸酶。）我们开发了一组特征明确的人类文化系统黑色素瘤细胞以及人类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和人类黑色素瘤细胞中雌二醇的核受体组织学正常的人类黑色素细胞（痣）。上述目标已取得重大进展。雌二醇有已被证明可诱导黑色素瘤细胞中的黄体酮受体并增加以生理剂量存在时的酪氨酸酶活性。的影响雌二醇和孕酮对黑色素瘤细胞生长和黑色素生成的影响 0ppear 受体介导。 (四)