Effect of selective progesterone receptor modulator for the proliferation and apoptosis in adenomyosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18156
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Chiba University
• Principal Investigator: Saito Yoshiko 千葉大学, 医学部附属病院, 医員 (20850754)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 子宮腺筋症 / 選択的プロゲステロン調節薬 / 子宮筋腫 / フマル酸ヒドラターゼ

Outline of Final Research Achievements

We clarified the inhibitory effect of ulipristal, a selective progesterone receptor modulator, on the proliferation of primary cultured adnomyosis cells in vitro. Next, we aimed to create a patient-derived adenomyosis xenograft model using a non-obese diabetes/severe combined immunodeficient mouse. However, during the couse of the experiment, ulipristal became difficult to obtain, and we were unable to complet the model. Instead, we identified a heterozygous pathogenic mutation in the FH gene, which encodes fumarate hydratase, in the uterine fibroids and myometrial tissue obtained from a woman with diffuse uterine leiomyomatosis.

Free Research Field

生殖内分泌学

Academic Significance and Societal Importance of the Research Achievements

子宮腺筋症細胞に対する選択的プロゲステロン受容体調節薬Ulipristalの増殖抑制効果が明らかになったことで、子宮腺筋症に対する新規治療薬としてUlipristalが候補となると考えられたが、海外でUlipristalの重篤な副作用報告が相次ぎ、臨床応用困難な状況となった。
一方、びまん性子宮平滑筋腫症におけるFH遺伝子のヘテロ接合性病的変異がみられることを明らかにすることができた。この結果は、びまん性子宮平滑筋腫症の病態解明に寄与すると考えられる。