Stojilkovic Stanko S, Bjelobaba Ivana, Zemkova Hana
Section on Cellular Signaling, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Front Endocrinol (Lausanne). 2017 Jun 9;8:126. doi: 10.3389/fendo.2017.00126. eCollection 2017.
Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM). These cells also express the hyperpolarization-activated and cyclic nucleotide-gated cation channels at the PM, as well as GABA, nicotinic, and purinergic P2X channels gated by γ-aminobutyric acid (GABA), acetylcholine (ACh), and ATP, respectively. Activation of these channels leads to initiation or amplification of the pacemaking activity, facilitation of calcium influx, and activation of the exocytic pathway. Gonadotrophs also express calcium-conducting channels at the endoplasmic reticulum membranes gated by inositol trisphosphate and intracellular calcium. These channels are activated potently by hypothalamic gonadotropin-releasing hormone (GnRH) and less potently by several paracrine calcium-mobilizing agonists, including pituitary adenylate cyclase-activating peptides, endothelins, ACh, vasopressin, and oxytocin. Activation of these channels causes oscillatory calcium release and a rapid gonadotropin release, accompanied with a shift from tonic firing of single APs to periodic bursting type of electrical activity, which accounts for a sustained calcium signaling and gonadotropin secretion. This review summarizes our current understanding of ion channels as signaling molecules in gonadotrophs, the role of GnRH and paracrine agonists in their gating, and the cross talk among channels.
促性腺激素细胞是腺垂体的嗜碱性细胞，专门用于在细胞内钙浓度升高时分泌促性腺激素。这些细胞会自发产生动作电位（APs），同时伴有电压门控钙内流，但其幅度不足以触发促性腺激素释放。促性腺激素细胞的自发兴奋性反映了其质膜（PM）上电压门控钠、钙、钾、非选择性阳离子传导和氯通道的表达。这些细胞在质膜上还表达超极化激活的环核苷酸门控阳离子通道，以及分别由γ-氨基丁酸（GABA）、乙酰胆碱（ACh）和ATP门控的GABA、烟碱和嘌呤能P2X通道。这些通道的激活会导致起搏活动的启动或放大、钙内流的促进以及胞吐途径的激活。促性腺激素细胞在内质网膜上也表达由三磷酸肌醇和细胞内钙门控的钙传导通道。这些通道被下丘脑促性腺激素释放激素（GnRH）强烈激活，而被几种旁分泌钙动员激动剂（包括垂体腺苷酸环化酶激活肽、内皮素、ACh、血管加压素和催产素）较弱地激活。这些通道的激活会导致振荡性钙释放和快速的促性腺激素释放，同时伴随着从单个动作电位的紧张性放电转变为周期性爆发型电活动，这导致了持续的钙信号传导和促性腺激素分泌。本综述总结了我们目前对促性腺激素细胞中作为信号分子的离子通道的理解、GnRH和旁分泌激动剂在其门控中的作用以及通道之间的相互作用。
