Adams Van L, Goodman Robert L, Salm A K, Coolen Lique M, Karsch Fred J, Lehman Michael N
Department of Physiology and Pharmacology, West Virginia University, Morgantown, 26506, USA.
Endocrinology. 2006 Oct;147(10):4843-51. doi: 10.1210/en.2006-0408. Epub 2006 Jul 20.
An increase in the response of GnRH neurons to estrogen negative feedback is responsible for seasonal anestrus in the ewe, but the underlying neural mechanisms remain largely unknown. Neural plasticity may play an important role because the density of synaptic input to GnRH neurons changes with seasons. Moreover, the transition from breeding to anestrous season requires thyroid hormones, which are also required for neuronal development. In the first experiment, we examined whether the decrease in synapses on GnRH neurons is critical for the transition to anestrus by comparing synaptic input in thyroidectomized and thyroid-intact controls, using electron microscopic analysis. Thyroidectomized ewes remained in the breeding season, but the number of synaptic contacts on their GnRH cells was not different from those in thyroid-intact ewes that were anestrus. The next experiment tested whether there was a seasonal change in morphology of the A15 dopaminergic neurons that mediate estrogen negative feedback during anestrus by analyzing synapsin-positive close contacts onto A15 neurons with confocal microscopy. There was a 2-fold increase in these close contacts onto dendrites of A15 neurons in anestrus and a corresponding increase in the length of A15 dendrites at this time of year. The increase in dendritic length was blocked by thyroidectomy, but this procedure did not significantly affect synaptic input to A15 neurons. These results provide initial evidence that the seasonal change in synapses on GnRH neurons is not sufficient for the transition into anestrus but that plasticity of the A15 dopaminergic neurons mediating estrogen negative feedback may contribute to this seasonal alteration.
促性腺激素释放激素（GnRH）神经元对雌激素负反馈反应的增强是母羊季节性发情停止的原因，但潜在的神经机制仍 largely 未知。神经可塑性可能起重要作用，因为输入到GnRH神经元的突触密度随季节变化。此外，从繁殖季节到发情停止季节的转变需要甲状腺激素，而甲状腺激素也是神经元发育所必需的。在第一个实验中，我们通过使用电子显微镜分析比较甲状腺切除的母羊和甲状腺完整的对照羊的突触输入，来研究GnRH神经元上突触的减少对于向发情停止转变是否至关重要。甲状腺切除的母羊仍处于繁殖季节，但其GnRH细胞上的突触接触数量与处于发情停止期的甲状腺完整母羊并无差异。下一个实验通过使用共聚焦显微镜分析突触素阳性紧密接触到A15神经元上的情况，来测试在发情停止期间介导雌激素负反馈的A15多巴胺能神经元的形态是否存在季节性变化。在发情停止期，这些紧密接触到A15神经元树突上的情况增加了2倍，并且在一年中的这个时候A15树突的长度相应增加。树突长度的增加被甲状腺切除术阻断，但该手术并未显著影响对A15神经元的突触输入。这些结果提供了初步证据，表明GnRH神经元上突触的季节性变化不足以转变为发情停止期，但介导雌激素负反馈的A15多巴胺能神经元的可塑性可能促成了这种季节性变化。
