Molecular mechanisms of androgen receptor functions

Abstract

The androgens testosterone (T) and dihydrotestosterone (DHT) are steroid hormones, which are necessary for development and maintenance of the functions of the male sex organs, including the prostate. Androgens also play an important role in benign abnormalities of the prostate and in the growth of prostate cancer. Prostate tumors, which are not yet metastatic, are treated with radiotherapy or by surgical removal of the complete prostate. Therapy of metastasized prostate cancer aims on inhibition of androgen action, by inhibtion of the production of T in the testis (chemical castration) and by administration of anti-androgens. T and DHT exert their function by specific binding as a ligand to the androgen receptor (AR). The AR is a member of the family of nuclear receptors. It is expressed in androgen target cells, and functions as a ligand induced transcription factor. In this thesis described research project focusses on several molecular mechanisms of AR functions. Chapter 1 gives an overview of the current knowledge on nuclear receptors in general and different aspects of AR functions in particular. Among the latter are: receptor structure, interaction with other proteins involved in transcription, the ligand-dependent interaction between the N-terminal domain (NTD) and the ligand binding C-terminal domain (LBD) of the AR (N/C interaction), expression of androgen-specific regulated genes, and the role of AR mutations in prostate cancer