HORMONAL REGULATION OF PROSTATE SPEClFlC ANTIGEN AND HUMAN GLANDULAR KALLlKRElN IN MALES AND FEMALES IN VIVO: EFFECTS OF ANDROGENS AND ANTIANDROGENS ON PLASMA

The PSA and hK2 genes are known to be regulated by androgens and progestins in vitro. To detennine if this also occurs in vivo, plasma and urinary PSA and hK2 were immunoassayed in 32 fernale-to-male transsexuals before, at 4 and at 12 months of testosterone treatment, as well as in 3 groups of rnale-tofernale transsexuals undergoing 3 types of androgen-suppressing therapy. Due to testosterone, serum and urinary PSA as well as urinary hK2 were upregulated dramatically (>go%) by the 4th month; serum hK2 remained undetectable. Conversely, the antiandrogen cyproterone acetate (CA), alone or in combination with estradiol, suppressed plasma and urinary PSA and hK2 (290%) either at 4 or 12 months of therapy. All changes were statistically significant (P<0.001) at 4 rnonths compared to baseline. The demonstrated in-vivo upreg ulation of PSA and hK2 by testosterone, and their in-vivo downregulation by CA may have clinical applications in hyperandrogenic females and prostate cancer patients. First and foremost, I would like to express rny watmest gratitude to my supervisor. Dr. Eleftherios P. Diamandis, for his guidance and support during the course of this study; his tremendous insight and enthusiasm provided the foundation for the success of this work. My gratitude also extends to our invaluable collaborators, Dr. Erik J. Giltay and Louis G. Gooren; without their meticulous collection and preparation of the clinical samples, this study would not have been possible. Speciaf thanks to the rnemben of my cornmittee. Dr. Alex Romaschin and Dr. Khosrow Adeli, for their mentorship and helpful advice. Dr. David Howarth and Dr. Andreas Scorilas provided their expertise for histochernical and statistical analyses. Many thanks to my fellow graduate students in our laboratory. from whose friendship and suggestions I have benefited a great deal. I wish to acknowledge Dr. Marc Mittelman for my initiation into the field of medical research. My warrnest thanks to my father, my brother and al1 my friends who provided me with a lot of support during my graduate studies. I dedicate this work ta the rnemory of my late Mother who has taught me to strive to reach rny goals and rny fui1 potential.