title: Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis.
abstract: The aromatization hypothesis asserts that testosterone (T) must be aromatized to estradiol (E2) to activate copulatory behavior in the male rat. In support of this hypothesis, the aromatization inhibitor, ATD, has been found to suppress male sexual behavior in T-treated rats. In our experiment, we first replicated this finding by peripherally injecting ATD (15 mg/day) or propylene glycol into T-treated (two 10-mm Silastic capsules) or control castrated male rats. In a second experiment, we bilaterally implanted either ATD-filled or blank cannulae into the medial preoptic area (MPOA) of either T-treated or control castrated male rats. With this more local distribution of ATD, a lesser decline in sexual behavior was found, suggesting that other brain areas are involved in the neurohormonal activation of copulatory behavior in the male rat. To determine whether in vivo ATD interacts with androgen or estrogen receptors, we conducted cell nuclear androgen and estrogen receptor binding assays of hypothalamus, preoptic area, amygdala, and septum following treatment with the combinations of systemic T alone. ATD plus T, ATD alone, and blank control. In all four brain areas binding of T to androgen receptors was significantly decreased in the presence of ATD, suggesting that ATD may act both as an androgen receptor blocker and as an aromatization inhibitor. Competitive binding studies indicated that ATD competes in vitro for cytosol androgen receptors, thus substantiating the in vivo antiandrogenic effects of ATD. Cell nuclear estrogen receptor binding was not significantly increased by exposure to T in the physiological range. No agonistic properties of ATD were observed either behaviorally or biochemically. Thus, an alternative explanation for the inhibitory effects of ATD on male sexual behavior is that ATD prevents T from binding to androgen receptors.
authors.affiliation: Department of Anatomy, Mount Sinai School of Medicine, CUNY, New York 10029.
authors.forename: M E
authors.initials: ME
authors.lastname: Kaplan
authors.forename: M Y
authors.initials: MY
authors.lastname: McGinnis
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000733:Androstatrienes / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003307:Copulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D011301:Preoptic Area / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects; D012686:Septal Nuclei / Q000187:drug effects; D012726:Sexual Behavior, Animal / Q000187:drug effects*
chemical_list: D000733:Androstatrienes; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C011658:androsta-1,4,6-triene-3,17-dione