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The Effects of a Brain-Enhanced Estradiol Delivery System on Testosterone and Androgen-Dependent Tissues. II. The Role of Testosterone

Center for Drug Discovery and Pharmatec, Inc. Alachua, Florida 32615
Center for Drug Discovery and the Department of Pharmacodynamics, University of Florida College of Pharmacy Gainesville, Florida 32610
Center for Drug Discovery, University of Florida College of Pharmacy Gainesville, Florida 32610

Address all correspondence and requests for reprints to: James W. Simpkins, Department of Pharmacodynamics, Box J-487, J. Hillis Miller Health Center, University of Florida, Gainesville, Florida 32610.

Abstract

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.

Received January 14, 1991.