Effects of Progesterone or Cyproterone Acetate on Androgen Uptake in the Brain,Pituitary and Peripheral Tissues 1

The uptake and distribution of radioactivity in specific regions of the brain as well as in the peripheral target tissues after the injection of labeled testosterone have been studied using both biochemical and histological techniques (1–7). The extensive research of Neumann and colleagues (8–9) has shown that the synthetic steroid cyproterone acetate (2-methylene pregna-4,6-dione-3,20-dione acetate) is a potent anti-androgen. This compound when implanted into the hypothalamus, significantly enhanced gonadotropin secretion (10), but no effects were observed on male sexual behavior (11). Progesterone has also been shown to antagonize a number of the actions of androgen on both central and peripheral tissues involved in reproduction (12). Since the effect of the anti-androgen cyproterone upon the uptake and retention of testosterone in the central nervous tissue is controversial (13), we studied the distribution or retention of radioactivity in the brain, the anterior pituitary, and in peripheral target tissues after the injection of 1,2-³H-testosterone into orchiectomized male rats pre-treated with cyproterone acetate or progesterone.

Materials and Methods. Twenty-five 35-day-old male Sprague-Dawley rats weighing approximately 160 g were orchiectomized and injected subcutaneously daily for 5 days with the following substances dissolved in 0.2 ml sesame oil: Group I (n = 9) was injected with sesame oil only, Group II (n = 8) with 4 mg of progesterone and Group III (n = 8) with 10 mg of cyproterone acetate. On Day 6, the rats were injected intravenously with 0.5 μg/100 g body weight, of 1,2-³H-testosterone, specific activity 45 Ci/mM (New England Nuclear), and decapitated after 1 hr. The animals were orchiectomized in order to prevent the competition of endogenous androgens with the exogenous radioactive androgen or its metabolites. Chronic treatments were employed to study the effects of progesterone or cyproterone acetate upon the radioactivity uptake, since anti-androgenic effects of these steroids have been shown after prolonged treatment (8, 9).