THU631 Steroyl-CoA Desaturase Is A Progesterone Receptor Target Gene In Uterine Leiomyoma

Abstract

Abstract Disclosure: A.S. Komorowski: None. A. Zuberi: None. J.S. Coon V: None. M.L. Anton: None. S.E. Bulun: None. P. Yin: None. Uterine leiomyomas (LM) are common benign neoplasms affecting approximately one in four reproductive-age women. LM can cause menorrhagia, dysmenorrhea, anemia, and infertility. Steroyl-CoA desaturase (SCD) is a delta-9 fatty acid desaturase which converts saturated fatty acids to monounsaturated fatty acids in a reaction that is critical to maintenance of fatty acid homeostasis. Prior work has demonstrated upregulation of SCD in multiple cancer types as part of lipid metabolic reprogramming, and SCD has been identified as a potential drug target for cancer and non-alcoholic steatohepatitis. Growth of LM tumors is progesterone-dependent, and we found that progesterone receptor (PR)-binding sites were enriched in the SCD gene locus. Normalized RNA-seq count demonstrated that knockdown of PR decreased SCD expression in LM cells. Further experiments with knockdown of PR in LM cells demonstrated decreased SCD expression on both quantitative real-time PCR and Western blot. Treatment of LM cells with progesterone for 6 hours lead to mild upregulation of SCD expression. In summary, steroyl-CoA desaturase, an enzyme involved in lipid homeostasis, is upregulated by progesterone and may represent a novel target for treatment of uterine LM. Presentation: Thursday, June 15, 2023