Relugolix reduces leiomyoma extracellular matrix production via the TGF β pathway

Adina Schwartz; Minnie Malik; Paul Driggers; William H Catherino

doi:10.1016/j.xfss.2024.12.004

Relugolix reduces leiomyoma extracellular matrix production via the TGF β pathway

F S Sci. 2024 Dec 27:S2666-335X(24)00084-3. doi: 10.1016/j.xfss.2024.12.004. Online ahead of print.

Authors

Adina Schwartz¹, Minnie Malik², Paul Driggers², William H Catherino³

Affiliations

¹ Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD.
² Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD.
³ Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD. Electronic address: william.catherino@usuhs.edu.

PMID: 39733929
DOI: 10.1016/j.xfss.2024.12.004

Abstract

Objective: To determine if the oral GnRH antagonist relugolix affects leiomyoma extracellular matrix production through the TGF β pathway DESIGN: Laboratory Study SUBJECTS: None.

Intervention: Exposure of human leiomyoma cells to TGF β and/or relugolix MAIN OUTCOME MEASURES: Production of TGF β, pSMAD2/3, SMAD2/3, COL1A1, FN1 and VCAN in treated and untreated leiomyoma cells RESULTS: TGF β3 production was decreased at 24 hours with relugolix at 10nM (0.80 + 0.09 fold, p 0.04) and 100nM (0.86 + 0.06 fold, p0.03) and at 48 hours with relugolix 1nM (0.86 + 0.05 fold, p0.01) and 100nM (0.86 + 0.06 fold, p0.04). pSMAD2/3 was decreased at 24 hours with relugolix 1nM (0.71 + 0.01 fold, p0.002), 10nM (0.68 + 0.01 fold, p0.001) and 100nM (0.41 + 0.10 fold, p0.004). When compared to relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1 and VCAN production with relugolix 1nM, 10nM and 100nM. At 48 hours, combination treatment resulted significantly increased COL1A1, FN1 and VCAN production with relugolix 10nM and 100nM.

Conclusion: Relugolix regulated leiomyoma size by decreasing COL1A1, FN1 and VCAN production. This effect is at least partly through the TGF β pathway.

Keywords: Leiomyoma; TGF β; extracellular matrix; relugolix.

Published by Elsevier Inc.