卵巣における新しいプロラクチン放出ペプチド作用機構の機能的組織学的研究

2000 Fiscal Year Annual Research Report

• Project/Area Number: 11671596
• Research Institution: University of Tsukuba
• Principal Investigator: 臼杵 哲 筑波大学, 臨床医学系, 助教授 (50092151)
• Co-Investigator(Kenkyū-buntansha): 塩田 正樹 熊本大学, 理学部, 教授 (80134526)
• Keywords: PrRP / 卵巣機能 / ゴナドトロピン / ホルモン産生

Research Abstract

Prolactin(PRL)-releasing peptide (PrRP)の卵巣機能に及ぼす作用機序の直接的・間接的作用を解明する目的で本研究を進めた。今回はラット,ウサギを用いて平成11年度での不足研究の追加と単層培養を中心にして各卵巣細胞レベルでの検討を行い,充分な基礎研究の後,インフォームド・コンセントを得てヒトでの解明に入った。さらに,まづ,PrRPの卵巣に於ける存在を明らかにした。さらに,PrRPの卵胞の発育と成熟,排卵および黄体の形成と退行に果たす役割を,In vivo ないし各時期に採取したラット卵巣細胞のIn vitro 培養液にPrRPを投与することによって各ステロイド産生能,レニン-アンジオテンシン-atrial natriuretic peptide system, Adenylate cyclase系,Cyclic nucleotides(Cyclic AMP,Cyclic GMP),Calcium channel,Insulin-like growth factor,卵巣細胞内Voltageに及ぼす影響,PTP,MAP kinases,Apoptosis,DNA合成酵素,DNA合成系および遺伝子レベルから検討した。同様に卵巣血管内皮系への影響も調べた。同時に,PrRPの LH,FSH,PRL,PACAP,GHおよびVIP作用に及ぼす影響についても明らかにした。PrRPは卵巣機能調節に重要な関わりを持っていることが明らかにされてきている。実験は概略的には計画的に進んでいる。

Research Products

• [Publications] Kotani E,Usuki S,Kondoh K,Kubo T.: "Pituitary adenylate cyclase-activating polypeptide (pacap) in the rat ovary. Eds..by H Ymashita and I Shibuya. Control Mechanisms of Stress and Emotion : Neuroendocrine-Based Studies. Amsterdam :"「Elsevier Science B.V.」. 21. 269-271 (2000)
• [Publications] Usuki S,Kondoh K,Kubo T.: "Plasma endothelin and LH-RH, LH, FSH, prolaction, progesterone, 17α-hydroxyprogesterone, estrone, 17β-estradiol, delta-4-androstenedione, testosterone, active renin, angiotensin-II and ANP levels in blood and LH, estrone 17β-estrdaiol and pregnenediol levels in urine of normal cycling women. "「Journal of Cardiovascular Pharmacology.」. 36(Suppl.1 to Issue 5). S421-S427 (2000)
• [Publications] Usuki S,Kondoh K,Kotani E,Kubo T.: "Effects of pituitary adenylate cyclase-activating polypeptide on progestin biosynthesis and the mitogen-activated protein kinases by cultured luteal cells from rat ovary. "「Recent Advances in Molecular and Endocrinology. Recent Advances in Endocrinology : Hormone-Receptor Interaction and Signaling.」. (in press.). (2000)
• [Publications] Nakamura J.,Okamura N.,Usuki S.,Bannai S..: "Inhibition of adenylyl cyclase activity in brain membrane fractions by arachidonic acid and related unsaturated fatty acids. "「Archives of Biochemistry and Biophysiology.」. (In press).
• [Publications] Usuki S.: "Tokishakuyakusan improves luteal insufficiency in fecund women and has no adverse effect on hormonal levels in blood or urine of women with normal menstrual cycles."「American Journal of Chinese Medicine,」. (In press).
• [Publications] Usuki S.,Kotani E..: "Tokishakuyakusan directly attenuates PACAP's luteolytic action on luteal function in the rat ovary."「American Journal of Chinese Medicine,」. (In press).
• [Publications] Usuki S.,Kotani E..: "Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on progestin biosynthesis in cultured luteal cells from rat ovary."「Gynecological Endocrinology.」. (In press).
• [Publications] Ohtaki T.,Shintani Y.,Honda S.,Matsumoto H.,Hori A.,Kanehashi K.,Yasuko Terao Y.,Kumano S.,Takatsu Y.,Masuda Y.,Ishibashi Y.,Watanabe T.,Asada M.,Yamada T.,Suenaga M.,Kitada C.,Usuki S.,Kurokawa T.,Onda H.,Nishimura O.,Fujino M.: "Metastasis suppressor gene Kiss-1 encodes choriostatin, the peptide ligand of hOT7T175 orphan G protein-coupled receptor."「Nature」. (In press).
• [Publications] Nakamura J.,Okamura N.,Usuki S.,Bannai S..: "Inhibition of adenylyl cyclase activity in mouse cerebellum membrane upon hydrolysis of triacylglycerols by triacylglycerol lipase, but not phopholipids by phopholipase A_2"「Archives of Biochemistry and Biophysiology.,」. (In press).