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在雄性大鼠中,来曲唑的产前给药可减少终纹床核和视交叉上核的体积及细胞数量,且与配偶偏好无关。

Prenatal administration of letrozole reduces SDN and SCN volume and cell number independent of partner preference in the male rat.

作者信息

Olvera-Hernández Sandra, Tapia-Rodríguez Miguel, Swaab Dick F, Fernández-Guasti Alonso

机构信息

Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Mexico.

Unidad de Microscopía, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico.

出版信息

Physiol Behav. 2017 Mar 15;171:61-68. doi: 10.1016/j.physbeh.2017.01.001. Epub 2017 Jan 3.

DOI:10.1016/j.physbeh.2017.01.001
PMID:28057567
Abstract

During development, the exposure to testosterone, and its conversion to estradiol by an enzyme complex termed aromatase, appears to be essential in adult male rats for the expression of typical male sexual behavior and female-sex preference. Some hypothalamic areas are the supposed neural bases of sexual preference/orientation; for example, male-oriented rams have a reduced volume of the sexually dimorphic nucleus (oSDN), while in homosexual men this nucleus does not differ from that of heterosexual men. In contrast, homosexual men showed a larger number of vasopressinergic cells in the suprachiasmatic nucleus (SCN). Interestingly, male rats perinatally treated with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), also showed bisexual preference and an increased number of vasopressinergic neurons in the SCN. However, this steroidal aromatase inhibitor has affinity for all three steroid receptors. Recently, we reported that the prenatal administration of the selective aromatase inhibitor, letrozole, produced a subpopulation of males with same-sex preference. The aim of this study was to compare the volume and number of cells of the SDN and SCN (the latter nucleus was immunohistochemically stained for vasopressin) between males treated with letrozole with same-sex preference, males treated with letrozole with female preference and control males with female preference. Results showed that all males prenatally treated with letrozole have a reduced volume and estimated cell number in the SDN and SCN, independent of their partner preference. These results indicate that the changes in these brain areas are not related to sexual preference, but rather to the effects of letrozole. The divergent results may be explained by species differences as well as by the critical windows during which the aromatase inhibitor was administered.

摘要

在发育过程中,暴露于睾酮及其通过一种名为芳香化酶的酶复合物转化为雌二醇,这对于成年雄性大鼠典型雄性性行为和雌性偏好的表达似乎至关重要。一些下丘脑区域被认为是性偏好/取向的神经基础;例如,雄性取向的公羊性二态核(oSDN)体积减小,而在同性恋男性中,该核与异性恋男性的核没有差异。相比之下,同性恋男性视交叉上核(SCN)中加压素能细胞数量更多。有趣的是,围产期用芳香化酶抑制剂1,4,6-雄甾三烯-3,17-二酮(ATD)处理的雄性大鼠也表现出双性恋偏好,且SCN中加压素能神经元数量增加。然而,这种甾体芳香化酶抑制剂对所有三种类固醇受体都有亲和力。最近,我们报道产前给予选择性芳香化酶抑制剂来曲唑会产生一群具有同性偏好的雄性。本研究的目的是比较有同性偏好的来曲唑处理雄性、有雌性偏好的来曲唑处理雄性和有雌性偏好的对照雄性之间,性二态核(SDN)和视交叉上核(SCN,后一个核用加压素进行免疫组织化学染色)的体积和细胞数量。结果表明,所有产前用 来曲唑处理的雄性,其 SDN 和 SCN 的体积和估计细胞数量均减少,与它们的伴侣偏好无关。这些结果表明,这些脑区的变化与性偏好无关,而是与来曲唑的作用有关。结果的差异可能由物种差异以及给予芳香化酶抑制剂的关键时期来解释。

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