Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells.

Journal Article (Journal Article)

The effects of progesterone on breast epithelial cells remain poorly defined with observations showing both proliferative and antiproliferative effects. As an example, progesterone levels correlate with increased epithelial cell proliferation, but there is discordance between the dividing cells and the cells with nuclear progesterone receptor expression. The release of paracrine growth factors from nuclear receptor-positive cells has been postulated as a mechanism, since in vitro studies show a lack of growth effect by progesterone in breast epithelial cells lacking nuclear receptors. This study examined possible nongenomic effects of progesterone in breast epithelia by using MCF-10A cells known to lack nuclear progesterone receptor expression. Treatment for 30-60 min with progesterone or the progestin, R5020, increased mitochondrial activity as shown by an increase in mitochondrial membrane potential (hyperpolarization) with a concordant increase in total cellular ATP. The reaction was inhibited by a specific progesterone receptor antagonist and not affected by the translation inhibitor cycloheximide. Progestin treatment inhibited apoptosis induced by activation of the FasL pathway, as shown by a decrease in sub-G(1) cell fraction during fluorescence-activated cell sorting and a decrease in caspase 3/7 levels. Progestin treatment did not alter the cell cycle over 48 h. Our study demonstrates a nongenomic action of progesterone on benign breast epithelial cells, resulting in enhanced cellular respiration and protection from apoptosis.

Full Text

Duke Authors

Cited Authors

  • Behera, MA; Dai, Q; Garde, R; Saner, C; Jungheim, E; Price, TM

Published Date

  • November 2009

Published In

Volume / Issue

  • 297 / 5

Start / End Page

  • E1089 - E1096

PubMed ID

  • 19690070

Pubmed Central ID

  • PMC2781356

Electronic International Standard Serial Number (EISSN)

  • 1522-1555

Digital Object Identifier (DOI)

  • 10.1152/ajpendo.00209.2009


  • eng

Conference Location

  • United States