| 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 |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| 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 / 分泌顆粒形成 / 下垂体前葉 / 免疫組織化学 / 精子形成 / 細胞・組織 / crinophagy |
|---|
| 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.
|
| 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。
|
