Female-specific pituitary gonadotrope dysregulation in mice with chronic focal epilepsy.
Female-specific pituitary gonadotrope dysregulation in mice with chronic focal epilepsy.
复制标题
慢性局灶性癫痫小鼠女性特异性垂体促性腺激素失调。
DOI：
10.1016/j.expneurol.2023.114389
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发表时间：
2023
影响因子：
5.3
通讯作者：
Christian-Hinman,CatherineA
中科院分区：
文献类型：
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作者：
Cutia,CathrynA;Leverton,LeannaK;Weis,KarenE;Raetzman,LoriT;Christian-Hinman,CatherineA
垂体前叶促性腺激素的释放对调节生殖内分泌功能至关重要。临床证据表明，癫痫患者的促性腺激素水平在癫痫发作后剧烈变化和慢性变化。尽管存在这种关系，垂体功能在临床前癫痫研究中仍然是一个很大程度上未被充分研究的途径。最近，我们发现雌性海马内kainic酸（IHKA）颞叶癫痫小鼠模型中垂体促性腺激素和促性腺激素释放激素（GnRH）受体基因的表达发生了变化。然而，循环促性腺激素水平尚未在癫痫动物模型中测量。在这里，我们评估了IHKA男性和女性体内促黄体生成素（LH）和促卵泡激素（FSH）的循环水平、GnRH受体（Gnrhr）基因表达以及对外源性GnRH的敏感性。尽管在IHKA小鼠中，无论雌雄，LH释放脉动模式的总体动态都没有变化，但在IHKA雌性小鼠中，基础和平均LH水平的发情与发情的变化更大，发情周期延长，中断。此外，IHKA雌性小鼠垂体对GnRH的敏感性增加，ergnrh的表达也较高。发情期对GnRH有超敏反应，发情期无。慢性癫痫发作严重程度与LH参数没有相关性，IHKA小鼠的FSH水平没有变化。这些结果表明，尽管在IHKA女性中存在垂体基因表达和GnRH敏感性的变化，但在该模型中，也可能存在代偿机制，有助于维持慢性癫痫状态下促性腺激素的释放。
Gonadotropin hormone release from the anterior pituitary is critical to regulating reproductive endocrine function. Clinical evidence has documented that people with epilepsy display altered levels of gonadotropin hormones, both acutely following seizures and chronically. Despite this relationship, pituitary function remains a largely understudied avenue in preclinical epilepsy research. Recently, we showed that females in the intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy displayed changes in pituitary expression of gonadotropin hormone and gonadotropin-releasing hormone (GnRH) receptor genes. Circulating gonadotropin hormone levels, however, have yet to be measured in an animal model of epilepsy. Here, we evaluated the circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), GnRH receptor (Gnrhr) gene expression, and sensitivity to exogenous GnRH in IHKA males and females. Although no changes in overall dynamics of pulsatile patterns of LH release were found in IHKA mice of either sex, estrus vs. diestrus changes in basal and mean LH levels were larger in IHKA females with prolonged, disrupted estrous cycles. In addition, IHKA females displayed increased pituitary sensitivity to GnRH and higherGnrhrexpression. The hypersensitivity to GnRH was observed on diestrus, but not estrus. Chronic seizure severity was not found to be correlated with LH parameters, and FSH levels were unchanged in IHKA mice. These results indicate that although there are changes in pituitary gene expression and sensitivity to GnRH in IHKA females, there may also be compensatory mechanisms that aid in maintaining gonadotropin release in the state of chronic epilepsy in this model.