Medroxyprogesterone acetate downregulates cytokine gene expression in mouse fibroblast cells

Molecular and Cellular Endocrinology
Dominique KoubovecJanet P Hapgood

Abstract

Although medroxyprogesterone acetate (MPA) is used as an injectable contraceptive, in hormone replacement therapy (HRT) and in treatment of certain cancers, the steroid receptors and their target genes involved in the actions of MPA are not well understood. We show that MPA, like dexamethasone (dex), significantly represses tumour necrosis factor (TNF)-stimulated interleukin-6 (IL-6) protein production in mouse fibroblast (L929sA) cells. In addition, MPA repressed IL-6 and IL-8 promoter-reporter constructs at the transcriptional level, via interference with nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1). Furthermore, like dex, MPA does not affect NFkappaB DNA-binding activity. We also observed significant transactivation by MPA of a glucocorticoid response element (GRE)-driven promoter-reporter construct in both L929sA and COS-1 cells. The MPA-induced nuclear translocation of the glucocorticoid receptor (GR), as well as the antagonistic effects of RU486, strongly suggest that the actions of MPA in these cells are mediated at least in part via the GR.

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Citations

May 5, 2005·Journal of the National Cancer Institute·V Craig Jordan
Aug 21, 2013·The Journal of Steroid Biochemistry and Molecular Biology·J P HapgoodJ M Rohwer
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Aug 30, 2005·Molecular and Cellular Endocrinology·Dominique KoubovecJanet Patricia Hapgood
Jul 24, 2015·American Journal of Reproductive Immunology : AJRI·Jennifer DeeseLut Van Damme
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Aug 20, 2019·Molecular and Cellular Endocrinology·Pablo H Cutini, Virginia L Massheimer
Mar 1, 2021·American Journal of Reproductive Immunology : AJRI·Refilwe P MolatlhegiLyle R McKinnon

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