ANDROGEN RECEPTOR AND REGULATION FACTORS IN SKIN

雄激素影响体内的许多细胞过程。在皮肤上， 毛囊(HF)和皮脂腺(SG)是 调节雄激素的作用。有几种皮肤病会受到 雄激素，如雄激素性脱发、粉刺、多毛症、苔藓 硬化症和萎缩症等。这些与雄激素相关的皮肤状况 影响数以百万计的男人、女人和各个年龄段的儿童。 这项建议研究的长远目标大致如下： 了解雄激素在调节这些皮肤中的生化作用 疾病，特别关注寻找更有效的药物来治疗 这些和其他与雄激素相关的疾病过程。到目前为止，3 影响雄激素受体(AR)的“调节”蛋白质 鉴定、分离、提取和部分纯化。具体的 目标包括进一步纯化、氨基酸测序和克隆 3个因子：抑制蛋白(IP)、转换因子(CF)和 核受体蛋白(NAP)。 用人皮肤HF和SG作为组织模型研究雄激素 中介过程，更好地理解精确的分子 机制可能导致更好的皮肤病治疗选择和 其他依赖激素的组织(即，发生的肿瘤形成过程 在前列腺、乳腺和其他生殖组织中)。 本方法包括使用人类头皮组织从男性和 接受头发移植手术的女性，特别是接受显微解剖的 HF和SG.雄激素受体(AR)是从HF和SG中提纯的。 用于生产抗体，以供进一步测序和克隆。AS 我们分离了两种形式的AR，一种是活性的单体AR，另一种是 无功能的“四聚体”复合体。进一步的方法包括：克隆 在表达载体lambda-gt11中表达的人皮肤AR cDNA， 并使用当前的分子方法对IP进行测序和克隆， Cf和午睡。这3个因素可以用来探索特定的信号 参与启动AR调节基因的转录。

Androgens influence many cellular processes in the body. In skin, the hair follicle (HF) and sebaceous glands (SG) are tissue structures which mediate androgen action. There are several skin diseases affected by androgens, such as androgenetic alopecia, acne, hirsutism, lichen sclerosis et atrophicus, etc. These androgen associated skin conditions affect millions of men, women and children of all ages. The broad long term objectives of the research in this proposal are: to understand the biochemical role androgens have in mediating these skin diseases, with specific focus on finding more effective agents to treat these and other androgen related disease processes. Thus far, 3 "regulatory" proteins that affect the androgen receptor (AR) have been identified, isolated, extracted, and partially purified. The specific aims include further purification, amino acid sequencing, and cloning of the 3 factors: inhibitor protein (IP), converting factor (CF), and nuclear acceptor protein (NAP). Using human HF and SG of skin as a tissue model to study androgen mediated processes, a better understanding of the precise molecular mechanisms may lead to better treatment options for skin diseases and other hormone dependent tissues, (i.e., tumorigenic processes that occur in prostate, breast, and other reproductive tissues). The present methodology includes use of human scalp tissue from men and women undergoing hair transplant surgery, specifically, microdissected HF, and SG. The androgen receptor (AR) was purified from HF and SG and used for production of antibodies for further sequencing and cloning. As well, two forms of the AR were isolated, an "active" monomeric AR, and a nonfunctional "tetramer" complex. Further methodology includes: cloning of human skin AR CDNAS expressed in the expression vector, lambda-gt11, and use of current molecular methodology to sequence and clone the IP, CF, and NAP. The 3 factors may be used to explore the specific signals involved in initiating transcription of AR regulated genes.