The role of estrogen receptor in development of benign prostatic hyperplasia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18094
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Oita University
• Principal Investigator: MIZOGUCHI Shinsuke 大分大学, 医学部, 客員研究員 (70751733)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 前立腺肥大症 / エストロゲンレセプター / 慢性炎症 / 肥満 / 線維化

Outline of Final Research Achievements

Estrogen, which is increased in obese patients, is considered to be one of the key factors in development of BPH and G protein-coupled estrogen receptor (GPER) has been reported to be implicated in symptomatic BPH. To elucidate a role of GPER signaling in development of BPH, we evaluated changes in prostatic weight and inflammatory profiles in the prostate by GPER inhibition using high fat diet induced obesity rat model.
HFD showed significantly increased body weight, visceral fat and prostatic weight as well as significant upregulation of gene expressions in GPER, IL1β, TGFβ compared to ND. In contrast, HFD treated by G15 demonstrated significantly decreased prostatic weight in association with downregulation of IL1β, TGFβ compared to HFD with placebo. These results suggest GPER signaling has an important role in development of BPH in obese patients. Therefore, GPER inhibition could be an therapeutic target of BPH with metabolic syndrome.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

前立腺肥大症は明らかな加齢性疾患であり、罹患率も高く、QoLへの影響もあり、高度高齢化社会を迎える我が国においても克服すべき疾患である。一方でその病態生理は明らかではなく、長期的な薬物療法や手術療法が必要となる症例も存在する。本研究は、肥満患者における前立腺肥大症の発症にGPERが関与している可能性をしめした。前立腺肥大症の発症にはストレスや慢性炎症など複合的な要因が関与していることが想定されている。エストロゲンレセプターの一つであるGPERは前立腺肥大症の発症に関連している可能性があり、前立腺肥大症の新たな病態生理の解明と、新規治療薬の開発の基盤となりうる。