THE EFFECTS OF A BRAIN-ENHANCED ESTRADIOL DELIVERY SYSTEM ON TESTOSTERONE AND ANDROGEN-DEPENDENT TISSUES .2. THE ROLE OF TESTOSTERONE

The present study was undertaken to evaluate the efficacy of an estradiol-chemical delivery system (E2-CDS) for the brain vs. estradiol benzoate (E2-BNZ) in suppressing serum testosterone (T) and weights of the ventral prostate and seminal vesicle in male rats. Also, the role of serum T in the weight reduction of androgen-dependent tissues observed after E2-CDS treatment was further evaluated in these studies. Intact male rats received a single iv injection of either E2-CDS at a dose of 1.0 mg/kg or an equimolar dose of E2-BNZ (0.95 mg/kg). Sera and tissue samples were collected 1, 7, 14, or 21 days after injection for determination of hormones and tissue weights. A single injection of E2-CDS suppressed serum T levels by 96%, 83%, 46%, or 63% 1, 7, 14, or 21 days after treatment, respectively. In contrast, an equimolar dose of E2-BNZ had no significant effect on serum T at any sampling time examined. Prostate weight was maximally reduced by 53% at 7 days and remained significantly suppressed by more than 31% throughout the 21-day time course. Similarly, seminal vesicle weight was reduced by 14% on day 1, maximally reduced by 41% on day 7 and remained significantly suppressed through day 21. In contrast, E2-BNZ was ineffective in inducing weight changes in either of these tissues. Serum PRL was significantly elevated through day 14, while E2 was elevated through day 7 by E2-CDS. Both the anterior pituitary and adrenal gland weights were stimulated by E2-CDS treatment. Testis weight was moderately reduced by both esters. In a subsequent study serum T was reduced by 98% and 97% 1 and 7 days, respectively, after E2-CDS treatment, and weights of the ventral prostate and seminal vesicle were reduced by 47% and 40%, respectively, at 7 days. In contrast, in rats treated with Silastic capsules containing T, the expected E2-CDS-induced weight regression was prevented in both prostate and seminal vesicles. These data indicate that the prolonged effects of E2-CDS on weights of androgen-dependent tissues are caused by its ability to produce profound suppression of the serum T concentration.