Progesterone receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine-induced matrix metalloproteinase 9 activity in vitro.

Published

Journal Article

Progesterone (P4) and the progestin, 17α-hydroxyprogesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical progesterone receptor (PGR) but instead a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyprogesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyprogesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small interfering RNA. Our findings highlight a possible novel role of PGRMC1 in mediating the effects of MPA and in modulating cytokine-induced MMP-9 activity in cytotrophoblast cells in vitro.

Full Text

Duke Authors

Cited Authors

  • Allen, TK; Feng, L; Grotegut, CA; Murtha, AP

Published Date

  • February 2014

Published In

Volume / Issue

  • 21 / 2

Start / End Page

  • 260 - 268

PubMed ID

  • 23813454

Pubmed Central ID

  • 23813454

Electronic International Standard Serial Number (EISSN)

  • 1933-7205

Digital Object Identifier (DOI)

  • 10.1177/1933719113493514

Language

  • eng

Conference Location

  • United States