Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany.
Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany; Center of Human and Molecular Biology (ZHMB), Saarland University, Homburg, Germany.
Cell Calcium. 2017 Nov;67:138-147. doi: 10.1016/j.ceca.2017.04.004. Epub 2017 May 3.
Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic-pituitary-gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i.e. in kisspeptin and gonadotropin-releasing hormone (GnRH) neurons. Kisspeptin neurons are depolarized by leptin via activation of TRPC channels and kisspeptin depolarizes GnRH neurons through TRPC4 activation. Recent studies have functionally identified TRPC channels also in gonadotrope cells in the anterior pituitary gland, which secrete gonadotropins in response to GnRH and thus regulate gonadal function. TRP channel expression in these cells exhibits remarkable plasticity and depends on the hormonal status of the animal. Subsequent functional analyses have demonstrated that TRPC5 in gonadotropes contributes to depolarization of the plasma membrane upon GnRH stimulation and increases the intracellular Ca concentration via its own Ca permeability and via the activation of voltage-gated Ca channels. However, conditional gene targeting experiments will be needed to unambiguously dissect the physiological role of TRPC channels in the different cell types of the reproductive axis in vivo.
瞬时受体电位 (TRP) 通道在激素分泌细胞的信号转导机制中发挥着重要的功能作用,最近它们与生殖生理学也有牵连。虽然表达研究已经证明了在下丘脑-垂体-性腺 (HPG) 轴的所有水平都有 TRP 通道的表达,但关于控制生殖的单个细胞中 TRP 通道作用的功能细节才刚刚开始出现。经典的 TRP(TRPC)通道在神经内分泌脑的生殖中心(即 kisspeptin 和促性腺激素释放激素 (GnRH) 神经元)中表达明显。瘦素通过激活 TRPC 通道使 kisspeptin 神经元去极化,而 kisspeptin 通过激活 TRPC4 使 GnRH 神经元去极化。最近的研究在垂体前叶的促性腺激素细胞中也功能鉴定了 TRPC 通道,这些细胞对 GnRH 的反应分泌促性腺激素,从而调节性腺功能。这些细胞中的 TRP 通道表达表现出显著的可塑性,并且取决于动物的激素状态。随后的功能分析表明,促性腺激素细胞中的 TRPC5 在 GnRH 刺激时有助于细胞膜去极化,并通过其自身的 Ca 通透性和通过激活电压门控 Ca 通道来增加细胞内 Ca 浓度。然而,需要进行条件性基因靶向实验才能明确地在体内生殖轴的不同细胞类型中解析 TRPC 通道的生理作用。