Restoration of male sexual behavior by adult exogenous estrogens in male aromatase knockout mice

Restoration of male sexual behavior by adult exogenous estrogens in male aromatase knockout mice
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DOI:
10.1016/j.yhbeh.2004.02.003
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发表时间:
2004-06-01
影响因子:
3.5
通讯作者:
Balthazart, J
Balthazart, J
中科院分区:
医学3区
文献类型:
--
作者:
Bakker, J;Honda, S;Balthazart, J

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我们之前发现,雄性芳香酶敲除 (ArKO) 小鼠在 CYP19 基因的外显子 1 和 2 上携带靶向突变,因此无法将雄激素芳香化为雌激素,在成年后表现出受损的性行为。为了确定这种损害是否是由于雌二醇缺乏对性行为的激活所致,我们在这里研究了雄性 ArKO 小鼠在接受苯甲酸雌二醇 (EB) 或丙酸二氢睾酮 (DHTP) 成年治疗后的雄性性交行为以及性相关气味的嗅觉研究。我们再次发现,性腺完整的 ArKO 雄性表现出明显的行为缺陷,影响了它们的雄性性交行为以及对挥发性体味的嗅觉调查,但不影响肮脏的床上用品的嗅觉调查。成人接受 EB 和雄激素 DHTP 治疗后,男性性交行为的缺陷在很大程度上得到纠正,这表明雌二醇对这种行为具有显着的激活作用。相比之下,对成年 ArKO 雄性进行 EB 治疗,无论是阉割的还是性腺完整的雄性,都不会刺激对挥发性体味的嗅觉研究,这表明这种损害可能是由于长期缺乏雌激素而在个体发育过程中缺乏适当的组织这种行为造成的。总之,目前的研究表明,雄性 ArKO 小鼠的性行为缺陷主要是由于雌激素缺乏对行为的激活造成的。这与早期对大鼠和雪貂进行的药理学研究形成鲜明对比,这些研究表明雌二醇对男性性行为具有强烈的组织作用。 (C) 2004 Elsevier Inc. 保留所有权利。
We previously found that male aromatase knockout (ArKO) mice that carry a targeted mutation in exons 1 and 2 of the CYP 19 gene and as a result cannot aromatize androgen to estrogen show impaired sexual behavior in adulthood. To determine whether this impairment was due to a lack of activation of sexual behavior by estradiol, we studied here male coital behavior as well as olfactory investigation of sexually relevant odors in male ArKO mice following adult treatment with estradiol benzoate (EB) or dihydrotestosterone propionate (DHTP). Again, we found that gonadally intact ArKO males show pronounced behavioral deficits affecting their male coital behavior as well as their olfactory investigation of volatile body odors but not that of soiled bedding. Deficits in male coital behavior were largely corrected following adult treatment with EB and the androgen DHTP, suggesting that estradiol has prominent activational effects on this behavior. By contrast, adult treatment with EB to either castrated or gonadally intact ArKO males did not stimulate olfactory investigation of volatile body odors, suggesting that this impairment may result from a lack of proper organization of this behavior during ontogeny due to the chronic lack of estrogens. In conclusion, the present studies suggest that the behavioral deficits in sexual behavior in male ArKO mice result predominantly from a lack of activation of the behavior by estrogens. This is in contrast with earlier pharmacological studies performed on rats and ferrets that have suggested strong organizational effects of estradiol on male sexual behavior. (C) 2004 Elsevier Inc. All rights reserved.