ANDROGEN RECEPTOR & REGULATION FACTORS IN SKIN

雄激素影响体内许多细胞过程。在皮肤中， 毛囊（HF）和皮脂腺（SG）是组织结构， 介导雄激素作用。有几种皮肤病的影响， 雄激素，如雄激素性脱发、痤疮、多毛症、苔藓 硬化和萎缩等。这些雄激素相关的皮肤病 影响到数百万男女老少。 这项建议的研究的长远目标是： 了解雄激素在介导这些皮肤中的生化作用， 疾病，特别注重寻找更有效的药物来治疗 这些和其他雄激素相关的疾病过程。迄今为止， 影响雄激素受体（AR）的“调节”蛋白质已经被发现。 鉴定、分离、提取和部分纯化。具体 目的包括进一步纯化，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）。 利用人皮肤HF和SG作为雄激素研究的组织模型 介导的过程，更好地了解精确的分子 机制可能会导致更好的治疗选择皮肤疾病， 其它激素依赖性组织，（即，肿瘤发生的过程 在前列腺、乳腺和其它生殖组织中）。 本发明的方法包括使用来自男性的人头皮组织， 接受毛发移植手术的女性，特别是，显微解剖 HF和SG。从HF和SG中纯化雄激素受体（AR）， 用于生产抗体以进一步测序和克隆。作为 两种形式的AR被分离出来，一种是“活性”单体AR， 非功能性“四聚体”复合物。其他方法包括：克隆 在表达载体中表达的人皮肤AR CDNAS， 并使用当前的分子方法学来测序和克隆IP， CF和NAP。这3个因素可用于探索特定信号 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.