Effects of the nonsteroidal inhibitor R76713 on testosterone-induced sexual behavior in the Japanese quail (Coturnix coturnix japonica). 1990

J Balthazart, and L Evrard, and C Surlemont
Laboratoire de Biochimie Générale et Comparée, Université de Liège, Belgium.

A new triazole derivative, R76713 (6-[4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H- benzotriazole), was recently shown to inhibit aromatase selectively without affecting other steroid-metabolizing enzymes and without interacting with estrogen, progestin, or androgen receptors. This compound was tested for its capacity to intefere with the induction of copulatory behavior by testosterone (T) in castrated Japanese quail (Coturnix coturnix japonica). In a first experiment, R76713 inhibited (range 0.01 to 1 mg/kg) the activation of sexual behavior by T silastic implants and hypothalamic aromatase activity in castrated male quail in a dose-dependent manner. The 5 alpha- and 5 beta- reductases of T were not systematically affected. Stereotaxic implantation of R76713 in the medial preoptic area similarly blocked the behavior activated by systemic treatment with T, demonstrating that central aromatization of androgen is implicated in the activation of behavior. These inhibiting effects of R76713 on behavior were observed when implants were placed in the medial part of the nucleus preopticus medialis, confirming the implication of this brain area in the control of male copulatory behavior. Finally, the behavioral inhibition produced by R76713 could be reversed by simultaneous treatment with a dose of estradiol, which was not behaviorally effective by itself. This suggests that the behavioral deficit induced by the inhibitor was specifically due to the suppression of estrogen production. This also shows that the activation of copulatory behavior probably results from the interaction of androgens and estrogens at the brain level, as the two treatments separately providing these hormonal stimuli (T with the aromatase inhibitor on one hand and a low dose of estradiol on the other hand) had almost no behavioral effects but they synergized to activate copulation when given concurrently. These data confirm the critical role of preoptic aromatase in the activation of reproductive behavior and demonstrate that R76713 is a useful tool for the in vivo study of estrogen-dependent processes.

UI MeSH Term Description Entries
D008297 Male Males
D011301 Preoptic Area Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM. Area Preoptica,Lateral Preoptic Area,Medial Preoptic Area,Preoptic Nuclei,Area Preopticas,Area, Lateral Preoptic,Area, Medial Preoptic,Area, Preoptic,Areas, Lateral Preoptic,Areas, Medial Preoptic,Areas, Preoptic,Lateral Preoptic Areas,Medial Preoptic Areas,Nuclei, Preoptic,Nucleus, Preoptic,Preoptic Area, Lateral,Preoptic Area, Medial,Preoptic Areas,Preoptic Areas, Lateral,Preoptic Areas, Medial,Preoptic Nucleus,Preoptica, Area,Preopticas, Area
D001931 Brain Mapping Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures. Brain Electrical Activity Mapping,Functional Cerebral Localization,Topographic Brain Mapping,Brain Mapping, Topographic,Functional Cerebral Localizations,Mapping, Brain,Mapping, Topographic Brain
D003307 Copulation Sexual union of a male and a female in non-human species. Copulations
D003370 Coturnix A genus of BIRDS in the family Phasianidae, order GALLIFORMES, containing the common European and other Old World QUAIL. Japanese Quail,Coturnix japonica,Japanese Quails,Quail, Japanese,Quails, Japanese
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012726 Sexual Behavior, Animal Sexual activities of animals. Mating Behavior, Animal,Sex Behavior, Animal,Animal Mating Behavior,Animal Mating Behaviors,Animal Sex Behavior,Animal Sex Behaviors,Animal Sexual Behavior,Animal Sexual Behaviors,Mating Behaviors, Animal,Sex Behaviors, Animal,Sexual Behaviors, Animal
D013739 Testosterone A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL. 17-beta-Hydroxy-4-Androsten-3-one,17-beta-Hydroxy-8 alpha-4-Androsten-3-one,8-Isotestosterone,AndroGel,Androderm,Andropatch,Androtop,Histerone,Sterotate,Sustanon,Testim,Testoderm,Testolin,Testopel,Testosterone Sulfate,17 beta Hydroxy 4 Androsten 3 one,17 beta Hydroxy 8 alpha 4 Androsten 3 one,8 Isotestosterone
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole

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