Research of D-aspartate synthetase involved in the production of testosterone in the testes

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16786
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Keiji Tomita 滋賀医科大学, 医学部, 助教 (30640148)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: テストステロン / アスパラギン酸

Outline of Final Research Achievements

In contrast to the consistently elevated testicular levels of L-Asp, HPLC analyses demonstrated that testicular level of D-Asp were initially low and rose to a plateau at 10 weeks of age. We found that DDO activity were highest just after birth and decreased with age, and were barely detectable or undetectable at 10 weeks of age. D-Asp was found to be localized in close proximity to the GFP-expressing acrosomes. DDO was expressed in mouse Sertoli cells at 2 weeks of age. Using in vitro spermatogenesis model, we determined exogenous D-Asp suppresses germ cell differentiation in mouse testis. We analyzed the spermatids of Acr-GFP Tg mouse; the cells of including D-Asp by HPLC, but we did not detect the production of D-Asp. Now we still did not prove the enzyme activity of D-aspartate synthetase.

Free Research Field

アンドロロジー

Academic Significance and Societal Importance of the Research Achievements

テストステロン合成に関する研究は、少子高齢化という社会的背景からも、男性不妊・LOH症候群・前立腺癌などの新規治療薬開発に向け、新たな知見が望まれる分野である。我々は、テストステロン合成を亢進する低分子化合物であるD型アスパラギン酸 (D-Asp)に着目し、精巣内でのD-Aspの局在・挙動を明らかにした。さらにマウス精子細胞の細胞質でD-Aspが合成されていることを示した。D-Aspは精巣内で合成されると予想され、この合成酵素を同定することでテストステロン合成に対する新たな介入手段を開発し、社会的にも問題となる諸疾患の新規治療法の開発につながる可能性がある。