Regulation of apoptosis in the prostate gland by androgenic steroids

The prostate gland requires androgenic steroids for its appropriate embryol ogical formation and postpubertal growth and, once at adult size, remains d ependent on a continuous supply of androgens for its vitality and function. A reduction of the levels of circulating androgens will rapidly induce apo ptosis of the cells of the prostate, leading to extensive glandular regress ion. Studies of rodent models of prostate response to castration have shown that there are some remarkable changes in the gene activity of prostate ep ithelial cells leading tip to apoptosis. There is now evidence for a critic al cell signaling pathway, regulated by c-fos expression, necessary for cas tration-induced apoptosis, as well as evidence that this signaling initiate s an abrupt and transient alteration in the synthesis of fas antigen, p53, bax and bcl-2 proteins in the androgen receptor-expressing prostate epithel ial cells, the cellular compartment that appears to be the most affected by castration. However, more recent studies suggest that these castration-ind uced effects on the prostate epithelial cells might be, at least in part, a n indirect response to a critical reduction in blood flow to the prostate g land that precedes the onset of epithelial cell apoptosis. The castration e ffects on blood flow to the prostate gland seem to be related to vascular d egeneration associated with apoptosis of a subset of prostate endothelial c ells.