Elucidation of the mechanism establishing sex difference in adrenal cortex cell proliferation by sex hormones

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyushu University
• Principal Investigator: Baba Takashi 九州大学, 医学研究院, 准教授 (40435524)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 副腎 / 性ステロイド / グルココルチコイド / 性差

Outline of Final Research Achievements

We have revealed that Ad4BP, a master regulator of adrenal development and function, induces sexual dimorphism (female > male) in global gene expression in the adrenocortical zona fasciculata cells. Furthermore, using CUT&RUN-seq, we have demonstrated that Ad4BP, as a transcription factor, directly controls over half of all genes expressed in the adrenocortical zona fasciculata cells.

We also investigated the impact of sexual dimorphism in global gene expression in adrenocortical zona fasciculata cells on other organs, particularly focusing on skeletal muscles. As a result, it was shown that heterozygous deficiency of Ad4BP leads to an increase in cross-sectional area of skeletal muscle fibers (thickening of muscle fibers). Based on these findings, sexual dimorphism in global gene expression in the adrenal glands in response to sex hormones confer sexual dimorphism in the production of glucocorticoids leading to sexual dimorphism in the thickness of muscle fibers.

Free Research Field

生殖内分泌学

Academic Significance and Societal Importance of the Research Achievements

この研究の主な学術的意義は、副腎の発生と機能司どる転写因子Ad4BPの発現量の性差が、副腎皮質束状層細胞における遺伝子発現に性差をもたらすことを明らかにした点です。この研究は、副腎の性差に関する新たな洞察を提供し、内分泌系と他の器官の関係性を理解する上で重要な役割を果たしています。特に、性ホルモンと副腎の相互作用がグルココルチコイドの産生や筋線維の太さに影響を与えることが示されたことは、生物学的な性差の理解に貢献します。これらの知見は、副腎機能や内分泌調節の研究において重要な基盤を提供し、将来的には新たな治療法や予防策の開発につながる可能性があります。