Expression of isotocin is male-specifically upregulated by gonadal androgen in the medaka brain
Expression of isotocin is male-specifically upregulated by gonadal androgen in the medaka brain
复制标题
青鳉脑中性腺雄激素对雄性特异的异产素表达上调
DOI：
10.1111/jne.12545
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发表时间：
2017
影响因子：
3.2
通讯作者：
Okubo K
中科院分区：
文献类型：
--
作者：
Yamashita J;Kawabata Y;Okubo K
催产素是一种主要在下丘脑视上核和室旁核合成的哺乳动物神经肽，介导了从分娩和哺乳到亲和和亲社会性的各种生理和行为过程。在啮齿类动物中的多项研究表明，催产素基因（Oxt）的表达受到雌激素的刺激，而雄激素没有明显的影响。然而，这一发现在所有的研究中并不一致，没有研究在其他动物中检查性类固醇对Oxtor及其直系同源物的调节。在本研究中，我们表明，在硬骨鱼，青鳉（Oryzias latipes）小细胞视前核中催产素（isotocin）基因（it）的表达（与哺乳动物视上核同源）是男性特异性上调性腺雄激素，其中在大细胞/小细胞视前核中表达（与哺乳动物室旁核同源）在两性中独立于性类固醇。没有一个表达它的神经元同时表达雄激素受体，这表明雄激素对表达的影响是间接的。我们发现kisspeptin基因kiss 2在男性大脑中的表达依赖于性腺雄激素，这增加了kiss 2神经元介导的雄激素依赖性表达的可能性。我们的数据还表明，响应雄激素而合成的异催产素肽通过轴突运输到垂体后叶，在外周发挥作用。考虑到女性中的表达水平高于男性，雄激素可能有助于补偿女性偏好的表达，以确保异催产素对两性的作用同样重要。这些结果出乎意料地与啮齿动物中报道的结果大不相同，表明性类固醇在Oxt/itexpression中的调节作用在进化过程中已经分化，可能伴随着催产素/异催产素作用的变化。
Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioural processes, ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation ofOxtor its orthologues in other animals. In the present study, we show that, in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost orthologue ofOxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male‐specifically up‐regulated by gonadal androgen, whereasitexpression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of theit‐expressing neurones appear to co‐express androgen receptors, suggesting that the effect of androgen onitexpression is indirect. We found that the expression of a kisspeptin gene,kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen‐dependent expression ofitmay be mediated bykiss2neurones. Our data also show that the isotocin peptide synthesised in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels ofitexpression are higher in females than in males, androgen may serve to compensate for the female‐biaseditexpression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids inOxt/itexpression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.