A novel experimental framework by using GnRH analogues to clarify the intracellular degradation processes of organelle outdated in their target cells/organs.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08505
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Asahikawa Medical College
• Principal Investigator: Watanabe Tsuyoshi 旭川医科大学, 医学部, 教授 (80220903)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 視床下部-下垂体-精巣系 / GnRH誘導体 / 性腺刺激ホルモン産生細胞 / 曲精細管上皮 / 分泌顆粒 / グラニン蛋白 / クリノファジー / 電子顕微鏡観察

Outline of Final Research Achievements

The putative differences in the effects of GnRH agonists and antagonists on their target organs/cells were analyzed in the present study. In the testicular seminiferous tubules, massive exfoliation of premature spermatids and anomalous multinucleated giant cells was observed in shortly after administration of GnRH agonist leuprorelin, whereas no discernible changes were found in those of GnRH antagonist degarelix-treated rats, although long term treatment with both types of GnRH analogues similarly induced a marked reduction of the epithelium. In the pituitary gonadotropes of degarelix-treated rats, crinophagy-like structures appeared and the residual hormones were gradually degraded. These findings clearly demonstrated the differences in the effects of GnRH agonists and antagonists on the target organs, and the comparison of their cytological and histological effects will provide a novel experimental framework to clarify the intracellular processes in the target organs.

Free Research Field

解剖学、細胞生物学、実験内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、臨床的に前立腺がんのホルモン治療薬として用いられているGnRH誘導体の徐放性製剤を投与したラット実験モデルを新たに確立し、その標的臓器である下垂体や精巣における組織学的変化を詳細に明らかにしたものである。本研究によって、精巣や下垂体に対するGnRH誘導体の薬理作用に関して新しい知見が付加され、将来的にはGnRH誘導体徐放性製剤の新たな活用法や望ましくない副作用の軽減方法の開発に寄与・貢献することが期待できる。