Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Exp Neurol. 2023 Jun;364:114389. doi: 10.1016/j.expneurol.2023.114389. Epub 2023 Mar 28.
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 higher Gnrhr expression. 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.
垂体前叶促性腺激素的释放对于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发生改变，无论是在癫痫发作后急性改变还是慢性改变。尽管存在这种关系，但在癫痫的临床前研究中，垂体功能仍然是一个很大程度上未被研究的途径。最近，我们发现海马内海人酸（IHKA）颞叶癫痫小鼠模型中的雌性动物表现出促性腺激素和促性腺激素释放激素（GnRH）受体基因在垂体中的表达变化。然而，在癫痫动物模型中尚未测量到循环促性腺激素激素水平。在这里，我们评估了 IHKA 雄性和雌性动物中黄体生成素（LH）和卵泡刺激素（FSH）的循环水平、GnRH 受体（Gnrhr）基因表达和对外源性 GnRH 的敏感性。尽管在任何性别的 IHKA 小鼠中均未发现 LH 释放脉冲模式的整体动力学变化，但在 IHKA 雌性动物中，发情期与间情期的基础和平均 LH 水平变化更大，其发情周期延长且中断。此外，IHKA 雌性动物表现出对 GnRH 的敏感性增加和 GnRhr 表达增加。在间情期而不是发情期观察到对 GnRH 的超敏反应。慢性癫痫发作严重程度与 LH 参数无关，IHKA 小鼠的 FSH 水平不变。这些结果表明，尽管在 IHKA 雌性动物中存在垂体基因表达和对 GnRH 的敏感性变化，但在该模型的慢性癫痫状态下，可能存在代偿机制有助于维持促性腺激素的释放。
