Relugolix reduces leiomyoma extracellular matrix production via the transforming growth factor-beta pathway

Abstract

Objective

To determine if the oral gonadotropin-releasing hormone antagonist relugolix affects leiomyoma extracellular matrix production through the transforming growth factor-beta (TGF-β) pathway.

Design

Laboratory study.

Subjects

None.

Exposure

Exposure of human leiomyoma cells to TGF-β and/or relugolix.

Main Outcome Measures

Production of TGF-β, pSMAD2/3, SMAD2/3, collagen 1A1 (COL1A1), fibronectin (FN1), and versican (VCAN) in treated and untreated leiomyoma cells.

Results

Transforming growth factor-beta 3 production decreased at 24 hours with relugolix 10 nM (0.80 ± 0.09-fold) and 100 nM (0.86 ± 0.06-fold) and at 48 hours with relugolix 1 nM (0.86 ± 0.05-fold) and 100 nM (0.86 ± 0.06-fold). pSMAD2/3 production decreased at 24 hours with relugolix 1 nM (0.71 ± 0.01-fold), 10 nM (0.68 ± 0.01-fold), and 100 nM (0.41 ± 0.10-fold). Compared with relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 1 nM, 10 nM, and 100 nM. At 48 hours, combination treatment resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 10 nM and 100 nM.

Conclusion

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