Prostate development

The prostate is the prototype of a hormone-dependent organ. During embryogenesis dihydrotestosterone triggers its development from the urogenital sinus. In this process, the interaction of the stromal and the epithelial compartments of the prostate gland are of crucial importance. The AR is first expressed in the stromal cells, which makes the cells responsive to dihydrotestosterone to stimulate proliferation and determine differentiation of the epithelial cells in a paracrine manner through the secretion of growth factors (Cunha 1984; 1992;Kratochwil 1986). Later, the AR is expressed in the epithelial cells and androgens can directly stimulate the growth of this cell type as well. The prostate finally grows to the normal size of about 20 cm3 coupled with the rise of serum levels of androgen that occurs during puberty with a prostatic weight doubling time of 2.8 years (Coffey and Isaacs 1981).

Growth and function of the prostate are critically dependent on the presence of androgens and the function of the AR. The major androgen required for this process is DHT. Its concentration is about 10 times higher within the prostate than the concentration of testosterone (Lamb et al. 1992) and in case of an inability to produce DHT - for example due to a defect of the 5a-reductase enzyme -the prostate does not develop, even if testosterone levels are normal (Griffin and Wilson 1989; Thigpen et al. 1992). In addition to the normal level of DHT, AR function is critical. Mutations that impair ligand activation or receptor function as a transcription factor also result in lack of prostate development (McPhaul and Griffin 1999).

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