Department of Experimental Medical Science, Unit Neurogastroenterology, BMC B11, Lund University, Sölvegatan 19, SE 22184 Lund, Sweden.
Department of Clinical Sciences, Division of Internal Medicine, Lund University, Sweden Lund University, Inga Marie Nilssons gata 32, SE 21428 Malmö, Sweden.
Auton Neurosci. 2015 Dec;193:104-7. doi: 10.1016/j.autneu.2015.10.001. Epub 2015 Oct 9.
Clinical observations have suggested repeated gonadotropin-releasing hormone (GnRH) exposure to cause intestinal dysfunction and loss of enteric neurons. This has been further studied and confirmed in a rat in vivo model involving iterated GnRH treatments. Mechanisms behind are enigmatic since no GnRH receptors are found to be expressed in enteric neurons neither in man nor rat. Both species, however, harbor substantial subpopulations of luteinizing hormone (LH) receptor-immunoreactive myenteric neurons which suggests that intestinal GnRH-induced neuropathy may be mediated by LH release.
To reveal if exposures of GnRH or LH to rat myenteric neurons in vitro cause neuronal loss.
Primary cultured adult rat myenteric neurons were exposed to single or repeated treatments of the GnRH analog buserelin or the LH analog lutrotropin alpha, and neuronal survival was determined by cell counting. Possible presence of GnRH- or LH receptor -immunoreactive neurons was determined by immunocytochemistry.
Exposure to the LH, but not the GnRH, analog caused significantly reduced neuronal survival. LH, but not GnRH, receptors were found to be expressed on cultured myenteric neurons.
Myenteric neurons express LH receptors in vitro and LH exposure causes reduced neuronal survival. This suggests that GnRH-induced enteric neuropathy in vivo is mediated by way of LH release and activation of enteric neuronal LH receptors.
临床观察表明，反复的促性腺激素释放激素（GnRH）暴露会导致肠道功能障碍和肠神经元丧失。这在涉及反复 GnRH 治疗的体内大鼠模型中得到了进一步研究和证实。其背后的机制尚不清楚，因为在人和大鼠的肠神经元中均未发现 GnRH 受体表达。然而，这两种物种都存在大量的黄体生成素（LH）受体免疫反应性肌间神经元亚群，这表明肠道 GnRH 诱导的神经病变可能是通过 LH 释放介导的。
揭示 GnRH 或 LH 对体外培养的大鼠肌间神经元的暴露是否会导致神经元丧失。
将原代培养的成年大鼠肌间神经元暴露于 GnRH 类似物布舍瑞林或 LH 类似物 lutrotropin alpha 的单次或重复处理中，并通过细胞计数确定神经元存活情况。通过免疫细胞化学法确定 GnRH 或 LH 受体免疫反应性神经元的存在。
暴露于 LH，但不是 GnRH 类似物，会导致神经元存活显著减少。发现 LH 受体而不是 GnRH 受体在培养的肌间神经元上表达。
肌间神经元在体外表达 LH 受体，LH 暴露会导致神经元存活减少。这表明体内 GnRH 诱导的肠神经病变是通过 LH 释放和激活肠神经元 LH 受体介导的。
