ANDROGEN RECEPTOR AND REGULATION FACTORS IN SKIN

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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.