女性荷爾蒙對於神經傳訊作用之探討

重症肌無力症（Myasthenia Gravis）是屬於一種神經肌肉的疾病，它會導致肌肉顫動、軟弱及容易疲勞。重症肌無力症的發生是因為自體免疫系統的紊亂，會產生抗體作用在突觸後神經肌接合點的尼古丁乙醯膽鹼受體。此症在年輕女性發病的比例相對於男性高很多，台灣女性和男性的比例約3比1，由於女性體內會受到雌激素的影響，因此本研究採用了雌二醇、黃體酮、以及泌乳素三種雌激素，以及雄性激素睪固酮，探討重症肌無力症好發在女性是否與雌激素相關。此外，如果在男性身上施打女性荷爾蒙會不會誘發重症肌無力症的症狀。 本研究採用小鼠橫膈肌張力實驗模式。在成年公鼠，橫膈肌投與雌激素觀察是否會誘發肌肉失活產生。同時也測試雄性激素睪固酮，比較雄性激素和雌激素對於肌肉張力的影響。本研究亦採用母鼠橫膈肌測試肌張力，評估雄性激素和雌激素對於肌張力的作用。研究結果證實影響肌張力的賀爾蒙為黃體酮，在小鼠肌張力測試中，外加黃體酮會誘發肌肉張力失活。此外，我們也採用小雞後頸肌實驗，結果顯示外加雌激素或雄性激素皆對肌肉收縮力無顯著的影響，此實驗結果顯示黃體酮誘發肌張力失活主要作用機制並不是因為乙醯膽鹼失活。另外我們也以新生大鼠脊髓切片配合全細胞膜片箝制電生理記錄，探討黃體酮對於離子電流之影響。研究結果發現黃體酮會抑制鈉離子電流。 本研究結果證實，抑制橫膈肌張力的賀爾蒙為黃體酮，先前已有研究論文提出重症肌無力症與乙醯膽鹼受體失活相關，但經由小雞後頸肌實驗的結果顯示黃體酮影響肌張力並非藉由乙醯膽鹼受體，而從新生大鼠脊髓切片電生理實驗證明出此激素影響神經對肌肉的傳訊作用是經由抑制鈉離子電流造成。

Myasthenia Gravis, a neuromuscular disease,leads to muscle twitching, weakness and fatigue.It is an autoimmune disorder in which antibodies form and blocks postsynaptic acetylcholine nicotinic receptors at the neuromuscular junction. Myasthenia Gravis most commonly affects young adult women than men (about 3:1 in Taiwan). The purpose of this study is to investigate the relation of female hormones and the high incidence of myasthenia gravisin women. We tested three female hormones including estradiol, progesterone, and prolactin. In addition, we also tested whether administration of the three hormones on men would induce the symptoms of myasthenia gravis. In this study, we used diaphragm preparation of male mice to examine the effect of estradiol, progesterone, and prolactin on muscle tension. We also administrated male hormone androsten to test muscle tension of diaphragmas compared with female hormones. In addition, we prepared diaphragm of female mice to test the muscle tension of female hormones as compared withandrosten. In this study, we found that progesterone decreased the muscle tension of diaphragm. We also used chickbiventer-cervicis muscle preparation to test the effect of female hormones and male hormone on muscle tension. We found that administrated female hormone or male hormone had no significant effect on muscle contraction, which means that the main mechanism of progesterone made muscle tension inactivation did not base on acetylcholine failed. In addition, we also tested the effects of progesterone using neonatal rat’s spinal cord slices and whole-cell patch clamp methods. The result shows that progesterone at 100 µM decreased Na+ current of the neurons.In summary, in mice muscle tension test, we found that progesterone affects muscle tension. The results of chick biventer-cervicis muscle experiment showed that progesterone decreased the muscle tension was not through acetylcholine receptors. Electrophysiologcial study indicates that progesterone decreases muscular tension by inhibition of Na+ current.