Role of androgen in prostate growth and regression: stromal-epithelial interaction

The prostate is a secretory gland in which secretions produced by its cells are transported through the ductal system and discharged into the urethra. Each prostatic ductal system can be traced from the opening in the urethra as a single tubular structure from which branches and sub-branches are formed in a manner like the branching pattern of a tree. Owing to the distance from the urethral orifice, regions of the prostatic ductal system can be classed into the proximal, intermediate, and distal regions. In the distal region, the tips of the ductal system (equivalent to the top of the tree), the epithelial cells are tall and columnar in shape, and active in cell division. Cells of the intermediate region (equivalent to the majority of the body of the tree) are also of tall and columnar type but are mitotically quiescent. Cells in this region are the only ones that have the ability to secrete. Cell death is not evident in these two regions. Cells in the proximal region, a region that is immediately adjacent to the urethra (equivalent to the tree trunk) are low cuboidal or flat in shape and are actively undergoing cell death. These observations indicate that cells in different regions of the prostatic ductal system are not the same, even though they are exposed to the same circulating level of androgen. The recognition of this regional heterogeneity in cell shape and activity in the ductal system has advanced our understanding of the basic biology of the prostate. For example, our understanding of the cellular mechanism of action of androgen in the prostate should be re-evaluated. In the past, the convention concept of androgen action has been a stimulatory one, and a depletion of this androgenic support leads to prostatic cell death. The recognition of a regional heterogeneity in cellular activity has created a situation in which all prostatic cells in the same prostatic ductal system are exposed to the same level of circulating androgen. However, these cells are not responding to the same amount of androgen in the same manner: some are multiplying while others are dying. These observations indicate that the effect of androgen vary according to the location of prostatic cells in the ductal system. A new concept of the role of androgen in prostatic growth, differentiation, and cell death is discussed.