Heterogeneity of Calcium Responses to Secretagogues in Corticotrophs From Male Rats.
Heterogeneity of Calcium Responses to Secretagogues in Corticotrophs From Male Rats.
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DOI：
10.1210/en.2017-00107
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发表时间：
2017-06-01
期刊：
影响因子：
4.8
通讯作者：
Shipston MJ
中科院分区：
文献类型：
--
作者：
Romanò N;McClafferty H;Walker JJ;Le Tissier P;Shipston MJ
同种型细胞反应中的异源性是许多生物系统的重要特征，并且已被证明在大多数垂体前叶激素细胞类型中是突出的。在这项研究中，我们分析异质性的反应下丘脑促肾上腺皮质激素细胞群的成年雄性大鼠。使用遗传编码的钙指示剂GCaMP6s，我们确定了这些细胞的促肾上腺皮质激素释放激素和垂体后叶素的细胞内钙反应。我们的实验揭示了显着的人口异质性，在这些肽的反应，在振幅和动态的反应，以及对不同浓度和持续时间的刺激的敏感性。然而，对同一细胞的重复刺激产生了非常一致的反应，表明这些反应在细胞水平上是确定的。我们还描述了类似的异质性的敏感性细胞抑制皮质酮。总之，我们的研究结果突出了很大程度的异质性的细胞机制，支配促肾上腺皮质激素细胞的生理刺激的反应，这可以提供一种机制，以扩大在人口水平的动态范围的反应，以适应不同的生理挑战。我们显示出显着的异质性在几个方面的钙反应下丘脑促肾上腺皮质激素的成年雄性大鼠。
Heterogeneity in homotypic cellular responses is an important feature of many biological systems, and it has been shown to be prominent in most anterior pituitary hormonal cell types. In this study, we analyze heterogeneity in the responses to hypothalamic secretagogues in the corticotroph cell population of adult male rats. Using the genetically encoded calcium indicator GCaMP6s, we determined the intracellular calcium responses of these cells to corticotropin-releasing hormone and arginine-vasopressin. Our experiments revealed marked population heterogeneity in the response to these peptides, in terms of amplitude and dynamics of the responses, as well as the sensitivity to different concentrations and duration of stimuli. However, repeated stimuli to the same cell produced remarkably consistent responses, indicating that these are deterministic on a cell-by-cell level. We also describe similar heterogeneity in the sensitivity of cells to inhibition by corticosterone. In summary, our results highlight a large degree of heterogeneity in the cellular mechanisms that govern corticotroph responses to their physiological stimuli; this could provide a mechanism to extend the dynamic range of the responses at the population level to allow adaptation to different physiological challenges. We show prominent heterogeneity in several aspects of the calcium responses to hypothalamic secretagogues in corticotrophs of adult male rats.