MECHANISM OF ESTROGEN ACTION ON MELANOCYTE FUNCTION

目前的临床、流行病学和实验证据

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)