ＧｎＲＨパルス頻度依存性特異的ゴナドトロピン発現機構の解明

2013 年度 研究成果報告書

• 研究課題/領域番号: 23592404
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 産婦人科学
• 研究機関: 島根大学
• 研究代表者: 金崎 春彦 島根大学, 医学部, 講師 (10325053)
• 研究分担者: 折出 亜希 島根大学, 医学部, 助教 (00423278)
• 研究期間 (年度): 2011 – 2013
• キーワード: GnRH / ゴナドトロピン

研究概要

高頻度GnRH刺激では低頻度GnRH刺激に比べてゴナドトロピン細胞内のPACAP及びPACAP受容体であるPAC1受容体発現が優位に増加する。またPACAPは単独でゴナドトロピンサブユニット発現能を持ち、その効果は濃度依存性であることから、下垂体局所で産生されるPACAPがオートクライン・パラクライン的に作用し、効果を発揮しているものと考えられた。PAC1受容体発現量の増加はPACAPの刺激効果を高めるだけでなく、GnRHの作用も増強させることが分かった。またPACAPはGnRHニューロン細胞株においてもその機能を修飾していることが分かった。

研究成果

• [雑誌論文] Expression of gonadotropin-inhibitory hormone receptors in mouse pituitary gonadotroph LβT2 cells and hypothalamic gonadotropin-releasing hormone-producing GT1-7 cells (2013)
  • 著者名/発表者名: Sukhbaatar U, Kanasaki H, Mijiddorj T, Oride A, Miyazaki K
  • 雑誌名: Endocr J 巻: 61 ページ: 253-34
• [雑誌論文] Kisspeptin induces expression of gonadotropin-releasing hormone receptor in GnRH-producing GT1-7 cells overexpressing G protein-coupled receptor 54 (2013)
  • 著者名/発表者名: Sukhbaatar U, Kanasaki H, Mijiddorj T, Oride A, Miyazaki K
  • 雑誌名: Gen Comp Endocrinol 巻: 194 ページ: 94-101
• [雑誌論文] Pituitary adenylate cyclase-activating polypeptide (PACAP) increases expression of the gonadotropin-releasing hormone (GnRH) receptor in GnRH-producing GT1-7 cells overexpressiong PACAP type I receptor (2013)
  • 著者名/発表者名: Kanasaki H, Mijiddorj T, Sukhbaatar U, Oride A, Miyazaki K
  • 雑誌名: Gen Comp Endocrinol 巻: 193 ページ: 95-102
• [雑誌論文] Circulating kisspeptin and pituitary adenylate cyclase-activating polypeptide (PACAP) do not correlate with gonadotropin serum levels (2013)
  • 著者名/発表者名: Kanasaki H, Purwana IN, Oride A, Mijiddorj T, Sukhbaatar U, Miyazaki K
  • 雑誌名: Gynecol Endocrinol 巻: 29 ページ: 583-587
• [雑誌論文] Possible role of PACAP and its PAC1 receptor in the differential regulation of pituitary LHβ- and FSHβ- subunit gene expression by pulsatile GnRH stimulation (2013)
  • 著者名/発表者名: Kanasaki H, Purwana IN, Miyazaki K
  • 雑誌名: Biol Reprod 巻: 88 ページ: 1-5
• [雑誌論文] Prolonged stimulation with thyrotropin-releasing hormone and pituitary adenylate cyclase-activating polypeptide desensitize their receptor functions in prolactin-producing GH3 cells (2013)
  • 著者名/発表者名: Mijiddorj T, Kanasaki H, Sukhbaatar U, Oride A, Purwana IN, Miyazaki K
  • 雑誌名: Mol Cell Endocrinol 巻: 365 ページ: 139-145
• [雑誌論文] Gonadotropin-inhibitory hormone inhibits GnRH-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 cells (2012)
  • 著者名/発表者名: Son YL, Ubuka T, Millar RP, Kanasaki H, Tsutsui K
  • 雑誌名: Endocrinology 巻: 153 ページ: 2332-2343
• [雑誌論文] Role of Neurokinin B and Dynorphin A in pituitary gonadotroph and somatolactotroph cell lines (2012)
  • 著者名/発表者名: Mijiddorj T, Kanasaki H, Purwana IN, Oride A, Sukhbaatar U and Miyazaki K
  • 雑誌名: Endocr J 巻: 59 ページ: 631-640
• [雑誌論文] Effects of estradiol and progesterone on gonadotropin LHβ- and FSHβ-subunit promoter activities in gonadotroph LβT2 cells (2012)
  • 著者名/発表者名: Kanasaki H, Purwana IN, Mijiddorj T, Sukhbaatar U, Oride A, Miyazaki K
  • 雑誌名: Neuro Endocrinol Lett 巻: 33 ページ: 608-613
• [雑誌論文] Effects of estradiol and progesterone on prolactin transcriptional activity in somatolactotrophic cells (2012)
  • 著者名/発表者名: 0Mijiddorj T, Kanasaki H, Purwana IN, Oride A, Sukhbaatar U and Miyazaki K
  • 雑誌名: Endocr J 巻: 59 ページ: 867-879
• [学会発表] Prolonger stimulation with thyrotropin-releasing hormone and pituitary adenylate cyclase-activating polypeptide desensitize their receptor functions in prolactin-producing GH3 cells (2013)
  • 著者名/発表者名: Haruhiko Kanasaki, Tselmeg Mijiddorj, Unurjargar Sukhbaatar, Aki Oride, Kohji Miyazaki
  • 学会等名: The Endocrine Society's 95^<th> annual meeting
  • 発表場所: San Francisco, CA(USA)
  • 年月日: 2013-06-17
• [学会発表] Stimulatory effect of pituitary adenylate cyclase-activating polypeptide (PACAP) and its PACAP type I receptor (PAC1R) on prolactin synthesis in rat pituitary somatolactotroph GH3 cells (2013)
  • 著者名/発表者名: Tselmeg Mijiddorj, Haruhiko Kanasaki, Unurjargar Sukhbaatar, Aki Oride, Kohji Miyazaki
  • 学会等名: The Endocrine Society's 95^<th> annual meeting
  • 発表場所: San Francisco, CA(USA)
  • 年月日: 2013-06-17
• [学会発表] Circulating kisspeptin and pituitary adenylate cyclase-activating polypeptide do not correlate with gonadotropin serum levels (2012)
  • 著者名/発表者名: Haruhiko Kanasaki, Aki Oride, Tselmeg Mijiddorj, Unurjargar Sukhbaatar, Kohji Miyazaki
  • 学会等名: 2nd World Conferance Kisspeptin
  • 発表場所: Tokyo
  • 年月日: 20121106-09
• [学会発表] Expression of the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) potentiates the effects of GnRH on gonadotropin subunit gene expression (2012)
  • 著者名/発表者名: Haruhiko Kanasaki, Aki Oride, Indri Purwana, Tselmeg Mijiddorj, Unurjargal Sukhbaatar, Kohji Miyazaki
  • 学会等名: The Endocrine Society's 94^<th> annual meeting
  • 発表場所: Houston, TX (USA)
  • 年月日: 2012-06-26
• [学会発表] GnRH-induced PACAP and PAC1 Receptor Expression in Pituitary Gonadotrophs : A Possible Role in the Regulation of Gonadotropin Subunit Gene Expression (2011)
  • 著者名/発表者名: Kanasaki H, Oride A, Purwana IN Mijiddorj T and Miyazaki K
  • 学会等名: The Endocrine Society's 93^<rd> annual meeting
  • 発表場所: Boston, MA (USA)
  • 年月日: 2011-06-24
• [学会発表] Follistatin, induced by thyrotropin-releasing hormone (TRH), plays no role in prolactin expression but affects gonadotropin FSHb expression as a paracrine factor in pituitary somatolactotroph GH3 cells (2010)
  • 著者名/発表者名: Kanasaki H, Oride A, Purwana IN, Miyazaki K
  • 学会等名: 14^<th> International Congress of Endocrinology (ICE2010)
  • 発表場所: Kyoto(Japan)
  • 年月日: 20100326-30
• [図書] Specific regulation of gonadotropin LHβ- and FSHβ-subunit gene expression by pulsatile GnRH stimulation. Gonadotropin-releasing hormone (GnRH): Production, Structure & Function (2013)
  • 著者名/発表者名: Haruhiko Kanasaki, Aki Oride Kohji Miyazaki
  • 総ページ数: 123-139
  • 出版者: Nova Scientific Press, Inc (Ney York)