EFFECTS OF THE NONSTEROIDAL INHIBITOR-R76713 ON TESTOSTERONE-INDUCED SEXUAL-BEHAVIOR IN THE JAPANESE-QUAIL (COTURNIX-COTURNIX-JAPONICA)
EFFECTS OF THE NONSTEROIDAL INHIBITOR-R76713 ON TESTOSTERONE-INDUCED SEXUAL-BEHAVIOR IN THE JAPANESE-QUAIL (COTURNIX-COTURNIX-JAPONICA)
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DOI：
10.1016/0018-506x(90)90039-z
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发表时间：
1990-12-01
影响因子：
3.5
通讯作者：
SURLEMONT, C
中科院分区：
文献类型：
--
作者：
BALTHAZART, J;EVRARD, L;SURLEMONT, C
一种新的三唑衍生物，R76713（6-[（4-氯苯基）（1H-1，2，4-三唑-1-基）甲基]-1-甲基-1H-苯并三唑），最近被证明可以选择性地抑制芳香酶，而不影响其他类固醇代谢酶，也不与雌激素、孕酮或雄激素受体相互作用。在去势的日本鹌鹑（C。C. japonica）。在第一个实验中，R76713以剂量依赖性方式抑制（范围0.01至1 mg/kg）T硅橡胶植入物对性行为的激活和去势雄性鹌鹑下丘脑芳香化酶活性。第五个阿尔法5. beta.- T还原酶没有受到系统性影响。立体定位植入R76713在内侧视前区同样阻止了T全身治疗激活的行为，表明雄激素的中枢芳构化与行为激活有关。当将植入物置于视前内侧核的内侧部分时，观察到R76713对行为的这些抑制作用，证实了该脑区在控制雄性交配行为中的意义。最后，由R76731产生的行为抑制可以通过同时给予一定剂量的雌二醇来逆转，雌二醇本身对行为没有影响。这表明抑制剂诱导的行为缺陷是由于雌激素产生的抑制。这也表明，交配行为的激活可能是由于雄激素和雌激素在大脑水平上的相互作用，因为分别提供这些激素刺激的两种治疗（一方面用芳香酶抑制剂T，另一方面用低剂量雌二醇）几乎没有行为效应，但当同时给予时，它们协同激活交配。这些数据证实了视前芳香化酶在生殖行为激活中的关键作用，并证明R76713是雌激素依赖性过程的体内研究的有用工具。
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 interfere with the induction of copulatory behavior by testosterone (T) in castrated Japanese quail (C. c. 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 R76731 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 specificially 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.