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

Reprod Sci. 2014 Feb;21(2):260-8. doi: 10.1177/1933719113493514. Epub 2013 Jun 27.

Abstract

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.

Keywords: inflammation; preterm delivery; progesterone; progesterone receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chorion / drug effects
  • Chorion / metabolism
  • Cytokines / pharmacology*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Extraembryonic Membranes / drug effects
  • Extraembryonic Membranes / metabolism
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / metabolism*
  • Membrane Proteins / physiology*
  • Progestins / pharmacology*
  • Receptors, Progesterone / physiology*

Substances

  • Cytokines
  • Membrane Proteins
  • PGRMC1 protein, human
  • Progestins
  • Receptors, Progesterone
  • MMP9 protein, human
  • Matrix Metalloproteinase 9