在本研究團隊先前的研究中發現，在雞初代腦下垂體細胞中給予過氧化酶體增值因子活化受體（peroxisome proliferator-activated receptors，PPARs）的促進劑和抑制劑，會分別誘導和抑制促黃體成熟激素次單位 β （luteinizing hormone subunit beta，LHB）基因轉錄和轉譯的表現。因此我們推論 LHB 基因的表現可能受到PPARs訊息傳遞路徑所調控。為了進一步的將我們的研究延伸至哺乳類動物細胞的系統中，首先我們利用七週大並且已性成熟之雌性 Sprague-Dawley 品系鼠的腦下垂體，培養成鼠初代腦下垂體細胞，並觀察其內生性 mRNA 和蛋白質的表現，發現在鼠初代腦下垂體細胞中，會表現本研究中所要探討的過氧化酶體增殖因子活化受體 γ（peroxisome proliferator-activated receptors γ，Pparg）、過氧化酶體增殖因子活化受體 α（peroxisome proliferator-activated receptors α，Ppara）和 Lhb基因等 mRNA和蛋白質的表現。接著利用 PPARs 促進劑 GW9578，作用於鼠初代腦下垂體細胞中，發現會增加 Lhb 基因轉錄和轉譯的作用。而高度表現人類 PPARG 基因，也發現鼠 Lhb 基因的表現也有顯著上升的情形。最後利用雙色冷光分析法檢測其 Lhb 基因啟動子的活性，也發現在高度表現人類 PPARG 的細胞中，Lhb 基因啟動子的活性也有顯著上升。綜合以上結果，我們推測鼠腦下垂體細胞中 Lhb 基因 mRNA 和蛋白質的表現，可能藉由過度表現人類PPARG進而提高。

In our previous studies, treatment of peroxisome proliferator activated receptor (PPARs) agonists and antagonists, respectively, induced and suppressed endogenous luteinizing hormone subunit beta (LHB) gene mRNA and protein levels in chicken primary culture of pituitary cells. Thus, we suggested the PPARs signal transduction pathway might regulate the LHB gene expression. In this study, we recruited to expand our research scope to the mammalian system. First, we established primary culture of rat pituitary cells from 7-week-old and sexually mature female Sprague-Dawley rats. To observe the endogenous mRNA and protein expression, we found the peroxisome proliferator-activated receptors γ (Pparg), peroxisome proliferator-activated receptors α (Ppara), and Lhb genes express in the primary culture of rat pituitary cells. Then we treated PPARs agonist, GW9578, in rat primary culture of pituitary cells. As the results, Lhb gene transcription and translation were increased. Exogenous expression human PPARG gene in primary culture of rat pituitary cells induced rat Lhb gene mRNA and protein levels. We used dual-luciferase assay to demonstrate human PPARG induced the activities of rat Lhb proximal promoter region. Taken together, these data suggested overexpression human PPARG might upregulate Lhb gene mRNA and protein expression levels in rat primary culture of pituitary cells.

論文審定書 i
致謝 ii
摘要 iii
Abstract iv
壹、緒論 1
貳、實驗材料與方法 7
參、結果 21
肆、討論 30
伍、參考文獻 33
附錄 42

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