EFFECT OF SUSTAINED ESTRADIOL RELEASE IN THE INTACT MALE-RAT - CORRELATION OF ESTRADIOL SERUM LEVELS WITH ACTIONS ON BODY-WEIGHT, SERUM TESTOSTERONE, AND PERIPHERAL ANDROGEN-DEPENDENT TISSUES

The differential effect of increasing serum estradiol on various param eters in the intact male rat was assessed through the use of subcutane ously implanted, hormone-laden pellets. The delivery systems were desi gned to release drug through bioerosion at a zero-order rate over a 12 -day time-course. Male Sprague-Dawley rats (190 to 220 g) were given e strogen pellets at increasing labeled strengths (0, 0.001, 0.01, 0.1, 1.0, 10, 50, and 100 mg). Animals were weighed at various intervals be fore and after implantation. At Day 6, 12, and 26 after drug administr ation, rats were examined for 4 additional parameters, including serum estradiol and testosterone concentrations and accessory organ weights (i.e., ventral prostate and seminal vesicles). Serum estradiol levels were consistent with pellet potency and lifetime. Increases in body w eight were suppressed 50% by circulating estradiol levels of approxima tely 200 pg/mL at Day 6, 250 pg/mL at Day 12, and 285 pg/mL at Day 26. On the other hand, suppression of serum testosterone was more sensiti ve and was decreased 50% by peripheral estrogen levels of 36, 43, and 51 pg/mL at Days 6, 12, and 26, respectively. Accessory organ weights essentially reflected serum testosterone levels as indicated by their similar ED(50) values: 50.5, 50.5, and 44.3 pg/mL for the ventral pros tate at Day 6, 12, and 26, respectively, and 48, 56, and 51.5 pg/mL fo r the seminal vesicle regression at Day 6, 12, and 26, respectively. T he data indicate the pellet used provided sustained plasma levels of h ormone and these constant peripheral levels exerted potent pharmacolog ical action. Initial body weight changes seemed to be less sensitive t o the action of estradiol than serum testosterone or derivative proper ties, such as accessory organ weight. Copyright (C) 1997 Elsevier Scie nce Inc.