Corticosterone (17 deoxycortisol) is a glucocorticoid with oral activity and produced by adrenal cortex, which plays an important role in regulating the neuronal function of limbic system (including hippocampus, prefrontal cortex and amygdala). Corticosterone increased Rab mediated AMPAR membrane trafficking through SGK induced phosphorylation of GDI [1].
Corticosterone has been shown to cause hippocampal damage in a number of ways; altering dendritic tree of hippocampal neurons, apoptosis of hippocampal neurons [2]and inhibition of adult neurogenesis in dentate gyrus[3]. Firstly, high concentrations of Corticosterone were required to induce neuronal death in mouse hippocampal neurons, and secondly, glial cells in cultures were refractory to Corticosterone -induced apoptosis. Corticosterone induced apoptosis in primary cultures of hippocampal neurons in a dose dependent manner. Significant apoptosis started to be seen with 50 μM Corticosterone, and the number of apoptotic cells increased with increase in Corticosterone concentration [4].
Corticosterone-treated male mice were more severe whole-body insulin resistance in the, the high blood insulin concentrations upon corticosterone treatment resulted in lower glucose production in male mice but not in female mice. Because GCs stimulate and insulin suppresses hepatic gluconeogenesis, it is hard to separate the contribution of these two factors in the control of EGP. Quinn et al[5] have shown that female mice have a higher hepatic susceptibility to GCs. Thus, more pronounced actions of GCs in female mice might overrule the inhibitory effect of insulin on EGP or, alternatively, the FBG levels of corticosterone-treated mice were at their lowest limit, which requires EGP to prevent symptomatic hypoglycemia. Corticosterone treatment had opposite effects on GCR in male and female mice. GCR tended to increase in female mice but tended to decrease in male mice. These findings confirm that peripheral insulin resistance was more severe in corticosterone-treated males than in corticosterone-treated females because the elevated insulin levels by corticosterone treatment should have increased GCR substantially in both sexes. Altogether, The sex-differential effects of high-dose corticosterone treatment on insulin sensitivity were mainly driven by the more pronounced insulin resistance of peripheral tissues in male mice [6].
References:
[1] Gasser PJ, et al. Corticosterone-sensitive monoamine transport in the rat dorsomedial hypothalamus: potential role for organiccation transporter 3 in stress-induced modulation of monoaminergic neurotransmission. J Neurosci. 2006 Aug 23;26(34):8758-8766.
[2] Liu B, Zhang H, Xu C, et al. Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons[J]. Brain research, 2011, 1375: 59-67.
[3] Yu I T, Lee S H, Lee Y S, et al. Differential effects of corticosterone and dexamethasone on hippocampal neurogenesis in vitro[J]. Biochemical and biophysical research communications, 2004, 317(2): 484-490.
[4] Latt H M, Matsushita H, Morino M, et al. Oxytocin inhibits corticosterone-induced apoptosis in primary hippocampal neurons[J]. Neuroscience, 2018, 379: 383-389.
[5] Quinn M A, Xu X, Ronfani M, et al. Estrogen deficiency promotes hepatic steatosis via a glucocorticoid receptor-dependent mechanism in mice[J]. Cell reports, 2018, 22(10): 2690-2701.
[6] Wei Y, Li W, Meng X, et al. Corticosterone Injection Impairs Follicular Development, Ovulation and Steroidogenesis Capacity in Mice Ovary[J]. Animals, 2019, 9(12): 1047.
Corticosterone (17 deoxycortisol) 是一种具有口服活性的糖皮质激素，由肾上腺皮质产生，对调节边缘系统（包括海马、前额叶皮层和杏仁核）的神经元功能具有重要作用。皮质酮通过 SGK 诱导的 GDI 磷酸化增加 Rab 介导的 AMPAR 膜运输[1]。
皮质酮已被证明会以多种方式引起海马体损伤；改变海马神经元的树突树，海马神经元细胞凋亡 [2] 并抑制成年齿状回神经发生[3]。首先，需要高浓度的皮质酮来诱导小鼠海马神经元中的神经元死亡，其次，培养物中的神经胶质细胞对皮质酮诱导的细胞凋亡具有抵抗力。皮质酮以剂量依赖性方式诱导海马神经元原代培养物的细胞凋亡。 50 μM 皮质酮开始观察到明显的细胞凋亡，凋亡细胞的数量随着皮质酮浓度的增加而增加[4]。
皮质酮治疗的雄性小鼠全身胰岛素抵抗更严重，皮质酮治疗后的高血液胰岛素浓度导致雄性小鼠的葡萄糖生成降低，但雌性小鼠则没有。因为 GCs 刺激而胰岛素抑制肝糖异生，所以很难区分这两个因素在 EGP 控制中的作用。 Quinn 等人[5] 表明，雌性小鼠对 GC 具有更高的肝脏易感性。因此，GCs 在雌性小鼠中更明显的作用可能会否决胰岛素对 EGP 的抑制作用，或者，皮质酮治疗小鼠的 FBG 水平处于最低限度，这需要 EGP 来预防症状性低血糖。皮质酮治疗对雄性和雌性小鼠的 GCR 有相反的影响。 GCR 在雌性小鼠中趋于增加，但在雄性小鼠中趋于降低。这些发现证实，外周胰岛素抵抗在皮质酮治疗的男性中比在皮质酮治疗的女性中更严重，因为皮质酮治疗升高的胰岛素水平应该在两种性别中都显着增加 GCR。总而言之，高剂量皮质酮治疗对胰岛素敏感性的性别差异影响主要是由雄性小鼠外周组织更明显的胰岛素抵抗驱动的[6]。