磷酸二酯酶四型抑制劑對日本鰻催熟卵巢發育之影響

磷酸二酯酶四型抑制劑對日本鰻催熟卵巢發育之影響
楊隆勝¹、黃歆皓¹、李玟翰¹、方珮蓁¹、黃永森^1*

1.      國立高雄大學 生命科學系

脊椎動物的卵細胞發育可分成促性腺激素-非依賴與-依賴兩期，分別由成長因子(GF)和促性腺激素(GTH)所主要控制；GTH刺激卵巢發育與合成性類固醇，GTH受體是屬於G蛋白偶聯受體(GPCRs)，GPCRs可活化腺苷酸環化酶(AC)產生第二信使cAMP或cGMP而活化磷酸激酶(PK) A，而GF大多經由PKB刺激細胞功能。GTH的作用可因磷酸二酯酶(PDE)降解cAMP和cGMP而下降，GF的刺激作用由PTEN降解PIP3而被下調。PDE家族有11個異構物，PDE-4主要表現在濾泡顆粒細胞，而PDE的活性可被PK所調節。鰻魚是高經濟的養殖魚種，但鰻苗完全依靠天然捕撈，研究鰻魚生殖生理有其重要性與意義。已證明腦下垂體研磨液(FPH)添加雄性素(T)，可使得鰻魚卵發育同步化。我們也證明添加T可抑制卵巢PTEN蛋白質的表現。鰻魚催熟並非所有的鰻魚都能成熟，顯示個體卵巢對FPH+T的敏感度不一。試驗PDE-4抑制劑(hesperetin, Hes, 橙皮素)是否可加強FPH+T對卵巢發育的刺激。鰻魚催熟過程中添加Hes (30mg/kg BW)，分別處理8針與後4針 (週/針)之後犧牲魚體量測性腺發育結果、卵徑分佈狀態與卵巢基因表現情形。結果發現: 相對於FPH+T組, 添加Hes可有效的刺激GSI與增加卵徑並縮小卵徑的分佈狀態，卵巢PDE-4、PTEN、GDF-9的表現也被提高，顯示可能有實際應用的的潛力。

關鍵字: 日本鰻，磷酸二酯酶，人工催熟，卵巢

Effects of PDE-4 inhibitor on the induced ovarian development in the Japanese eel

Long-Shen Yang¹, Shin-How Huang¹, Wen-Han Lee¹, Pei-Jan Fang¹, Yung-Sen Huang^1*

1.      National University of Kaohsiung, Department of Life Science

The ovary in the Mammal is stimulated by gonadotropins (GTH) and growth factors (GF), their stimulatory effects are mainly provoked by cAMP and/or PIP3. The signaling molecules are down regulated by PDE and/or PTEN, respectively. The family of PDE comprises of 11 isoforms, PDE-4 is almost located in the ovarian granulosa cells. Eel is very important culture species in Taiwan, but the juvenile one are totally caught from the wild. There are still many problems on the eel artificial propagation, one of them is multiple injections of pituitary extracts (PE) leads an asynchronous development of eggs as well as failure of fertilization. It has showed the supplement of androgen (T) in PE can ameliorate the asynchronous development in treated ovaries, our data indicated that T suppressed the expression of PTEN. This work target if PDE-4 inhibitor enhances the stimulatory effects of PE+T. Eels are treated with hesperetin (Hes, a PDE-4 inhibitor) for 8 weeks or for the last 4 weeks. The results indicated that supplement of Hes could potent the stimulatory of PE on GSI and also synchronize the oocyte development on the diameters.              

Key words: Japanese eel, PDE, artificial maturation, ovary