Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons.
Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons.
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DOI：
10.1371/journal.pone.0159640
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hatt H
中科院分区：
文献类型：
--
作者：
Kanageswaran N;Nagel M;Scholz P;Mohrhardt J;Gisselmann G;Hatt H
性类固醇激素孕酮和雌二醇对月经周期和怀孕期间的生理和行为的影响是众所周知的。一些研究表明，嗅觉性能的变化与周期性波动类固醇激素水平的女性。女性性类固醇如何调节嗅觉信号的确切机制的知识是有限的。由孕酮和雌二醇通过与不同受体的相互作用介导的许多不同的已知基因组和非基因组作用可能是这种调节的原因。来自鼠嗅上皮（OE）和嗅觉受体神经元（ORN）的下一代基于测序的RNA-Seq转录组数据揭示了几种膜促甲状腺激素受体和雌二醇受体Gpr 30的表达。已知这些受体通过与G蛋白的相互作用介导快速的非基因组效应。RT-PCR和免疫组织化学染色结果提供了ORN中的雌二醇和雌二醇受体的证据。这些数据支持的假设，类固醇激素能够调节气味诱发的活动的ORN。在这里，我们验证了这一假设，通过调查类固醇激素的影响，淹没电嗅觉和全细胞膜片钳记录的ORN。这是第一次，我们证明，性类固醇激素孕酮和雌二醇降低气味诱发的信号在低纳摩尔浓度的小鼠OE和ORN。因此，这两种性类固醇都可以通过膜上的雌激素受体和雌二醇受体Gpr 30快速调节ORN的气味反应性。
The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30.