The vomeronasal organ (VNO), the sensory organ of the mammalian accessory olfactory system, mediates the activation of sexually dimorphic reproductive behavioral and endocrine responses in males and females. It is unclear how sexually dimorphic and state-dependent responses are generated by vomeronasal sensory neurons (VSNs). Here, we report the expression of the transient receptor potential (TRP) channel Trpm4, a Ca2+-activated monovalent cation channel, as a second TRP channel present in mouse VSNs, in addition to the diacylglycerol-sensitive Trpc2 channel. The expression of Trpm4 in the mouse VNO is sexually dimorphic and, in females, is tightly linked to their reproductive cycle. We show that Trpm4 protein expression is upregulated specifically during proestrus and estrus, when female mice are about to ovulate and become sexually active and receptive. The cyclic regulation of Trpm4 expression in female VSNs depends on ovarian sex hormones and is abolished by surgical removal of the ovaries (OVX). Trpm4 upregulation can be restored in OVX mice by systemic treatment with 17ß-estradiol, requires endogenous activity of aromatase enzyme, and is strongly reduced during late pregnancy. This cyclic regulation of Trpm4 offers a neural mechanism by which female mice could regulate the relative strength of sensory signals in their VSNs, depending on hormonal state. Trpm4 is likely to participate in sex-specific, estrous cycle-dependent and sex hormone-regulated functions of the VNO, and may serve as a previously unknown genetic substrate for dissecting mammalian sexually dimorphic cellular and behavioral responses.

中文翻译：

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卵巢性激素驱动的女性犁鼻神经元中Trpm4表达的循环调节。

雌性哺乳动物副嗅觉系统的感觉器官即犁鼻鼻器官（VNO）介导男性和女性的性双态生殖行为和内分泌反应的激活。尚不清楚犁鼻感觉神经元（VSN）如何产生性二态性和状态依赖性反应。在这里，我们报告的瞬态受体电位（TRP）通道Trpm4，Ca2 +激活的单价阳离子通道，作为小鼠VSN中存在的第二个TRP通道的表达，除了对二酰基甘油敏感的Trpc2通道。小鼠VNO中Trpm4的表达具有性别双态性，在雌性动物中，Trpm4的表达与其生殖周期紧密相关。我们显示Trpm4蛋白表达在发情期和发情期特别上调，当雌性小鼠即将排卵并变得性活跃并易于接受时。女性VSN中Trpm4表达的周期性调节取决于卵巢性激素，并且通过手术切除卵巢（OVX）取消。通过用17ß-雌二醇进行全身治疗，可以在OVX小鼠中恢复Trpm4的上调，需要内源性芳香化酶的活性，并且在妊娠晚期会大大降低。Trpm4的这种循环调节提供了一种神经机制，雌性小鼠可以通过这种机制调节其VSN中感觉信号的相对强度，具体取决于激素状态。Trpm4可能参与VNO的性别特异性，发情周期依赖性和性激素调节功能，并且可以作为解剖哺乳动物性双态细胞和行为反应的先前未知的遗传底物。女性VSN中Trpm4表达的周期性调节取决于卵巢性激素，并且通过手术切除卵巢（OVX）取消。通过用17ß-雌二醇进行全身治疗，可以在OVX小鼠中恢复Trpm4的上调，需要内源性芳香化酶的活性，并且在妊娠晚期会大大降低。Trpm4的这种循环调节提供了一种神经机制，雌性小鼠可以通过这种机制调节其VSN中感觉信号的相对强度，具体取决于激素状态。Trpm4可能参与VNO的性别特异性，发情周期依赖性和性激素调节功能，并且可以作为解剖哺乳动物性双态细胞和行为反应的先前未知的遗传底物。女性VSN中Trpm4表达的周期性调节取决于卵巢性激素，并且通过手术切除卵巢（OVX）取消。通过用17ß-雌二醇进行全身治疗，可以在OVX小鼠中恢复Trpm4的上调，需要内源性芳香化酶的活性，并且在妊娠晚期会大大降低。Trpm4的这种循环调节提供了一种神经机制，雌性小鼠可以通过这种机制调节其VSN中感觉信号的相对强度，具体取决于激素状态。Trpm4可能参与VNO的性别特异性，发情周期依赖性和性激素调节功能，并且可以作为解剖哺乳动物性双态细胞和行为反应的先前未知的遗传底物。