Detailed mechanisms of androgen action on the prostate are not entirely understood. In some tissues, androgen action does not directly depend on testosterone, the principal circulating androgen. Instead testosterone is first reduced to dihydrotestosterone (DHT) by the action of the enzyme 5a-reductase. For example, during embryogenesis, testosterone induces differentiation of the Wolfian duct into the epididymis, vas deferens, and seminal vesicles.

In contrast, development of the prostate from the urogenital sinus and the differentiation of the external genitalia depend on DHT. Furthermore, in adults the main intraprostatic androgen is DHT, while other physiological functions like libido and fertility depend on testosterone. This suggests that each hormone may selectively regulate the transcription of specific target genes. Little is known regarding specific genes or gene networks that are activated or repressed in response to each of these hormones. Availability of safe and potent inhibitors of the enzyme 5a-reductase provides a unique opportunity to study the extent to which androgen-dependent gene expression in the human prostate is contingent upon the action of DHT or testosterone.

Using DNA microarray, we are profiling gene expression in the human prostate treated with finasteride (5a-reductase inhibitor that inhibits the conversion of testosterone into DHT) and goserelin acetate (an agent that inhibits the release of LH from the pituitary gland decreasing the levels of both testosterone and DHT to castration levels).

Our goals are to:

• Study the pattern of gene expression in the human prostate in response to total and partial androgen deprivation

• Determine if in the human prostate, there are genes that are selectively or primarily regulated by testosterone

• Determine if in the human prostate, there are genes that are selectively or primarily regulated by DHT

Principal Investigator:  Elie Benaim, M.D.

For more information about the Department of Urology, contact:

Phone: 214-648-4765, FAX: 214-648-4789

Mailing Address:  5323 Harry Hines Blvd., J8.148, Dallas, TX  75390-9110