title: The effects of a brain-enhanced estradiol delivery system on testosterone and androgen-dependent tissues. II. The role of testosterone.
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.
authors.affiliation: Center for Drug Discovery, University of Florida College of Pharmacy, Gainesville 32610.
authors.forename: W R
authors.initials: WR
authors.lastname: Anderson
authors.forename: M H
authors.initials: MH
authors.lastname: Rahimy
authors.forename: M E
authors.initials: ME
authors.lastname: Brewster
authors.forename: N
authors.initials: N
authors.lastname: Bodor
authors.forename: J W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D000311:Adrenal Glands / Q000033:anatomy & histology; D000818:Animals; D001812:Blood-Brain Barrier; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000033:anatomy & histology; D011388:Prolactin / Q000097:blood; D011467:Prostate / Q000033:anatomy & histology* / Q000187:drug effects; D011726:Pyridinium Compounds / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000033:anatomy & histology* / Q000187:drug effects; D013737:Testis / Q000033:anatomy & histology; D013739:Testosterone / Q000097:blood* / Q000494:pharmacology
chemical_list: D004095:Dihydropyridines; D011726:Pyridinium Compounds; C051867:estradiol 17-dihydrotrigonelline; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin