Brain Health Research Institute and Department of Biological Sciences, Kent State University, Kent, OH, United States.
School of Biomedical Sciences, Kent State University, Kent, OH, United States.
Front Endocrinol (Lausanne). 2023 Oct 12;14:1212854. doi: 10.3389/fendo.2023.1212854. eCollection 2023.
The neuroendocrine control of ovulation is orchestrated by neuronal circuits that ultimately drive the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus to trigger the preovulatory surge in luteinizing hormone (LH) secretion. While estrogen feedback signals are determinant in triggering activation of GnRH neurons, through stimulation of afferent kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V neurons), many neuropeptidergic and classical neurotransmitter systems have been shown to regulate the LH surge. Among these, several lines of evidence indicate that the monoamine neurotransmitter serotonin (5-HT) has an excitatory, permissive, influence over the generation of the surge, activation of type 2 5-HT (5-HT) receptors. The mechanisms through which this occurs, however, are not well understood. We hypothesized that 5-HT exerts its influence on the surge by stimulating RP3V neurons in a 5-HT receptor-dependent manner.
We tested this using kisspeptin neuron-specific calcium imaging and electrophysiology in brain slices obtained from male and female mice.
We show that exogenous 5-HT reversibly increases the activity of the majority of RP3V neurons. This effect is more prominent in females than in males, is likely mediated directly at RP3V neurons and requires activation of 5-HT receptors. The functional impact of 5-HT on RP3V neurons, however, does not significantly vary during the estrous cycle.
Taken together, these data suggest that 5-HT receptor-mediated stimulation of RP3V neuron activity might be involved in mediating the influence of 5-HT on the preovulatory LH surge.
排卵的神经内分泌控制是由神经元回路协调的，这些回路最终驱动下丘脑释放促性腺激素释放激素（GnRH），以触发黄体生成素（LH）分泌的促排卵激增。虽然雌激素反馈信号在触发 GnRH 神经元的激活中起决定作用，但通过刺激第三脑室前室周区（RP3V 神经元）的传入 kisspeptin 神经元，许多神经肽和经典神经递质系统已被证明可调节 LH 激增。在这些系统中，有几条证据表明单胺神经递质 5-羟色胺（5-HT）对激增的产生具有兴奋性、许可性的影响，激活 5-HT 受体 2 型（5-HT2 受体）。然而，这种情况发生的机制尚不清楚。我们假设 5-HT 通过以 5-HT 受体依赖的方式刺激 RP3V 神经元来发挥其对激增的影响。
我们使用雄性和雌性小鼠脑片的 kisspeptin 神经元特异性钙成像和电生理学来测试这一点。
我们表明，外源性 5-HT 可可逆地增加大多数 RP3V 神经元的活性。这种作用在雌性中比在雄性中更为明显，可能直接在 RP3V 神经元中介导，并需要 5-HT 受体的激活。然而，5-HT 对 RP3V 神经元的功能影响在发情周期中并没有显著变化。
综上所述，这些数据表明，5-HT 受体介导的 RP3V 神经元活性刺激可能参与介导 5-HT 对促排卵 LH 激增的影响。
