Unopposed Estrogen Supplementation/Progesterone Deficiency in Post‐Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue‐Specific Manner in the Rat

Unopposed Estrogen Supplementation/Progesterone Deficiency in Post‐Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue‐Specific Manner in the Rat

American Journal of Reproductive Immunology, August 2015

26307150

Stanislava Stanojević, Vesna Kovačević‐Jovanović, Mirjana Dimitrijević, Vesna Vujić, Ivana Ćuruvija, Veljko Blagojević, Gordana Leposavić

The influence of unopposed estrogen replacement/isolated progesterone deficiency on macrophage production of pro-inflammatory/anti-inflammatory mediators in the post-reproductive age was studied. Considering that in the rats post-ovariectomy the circulating estradiol, but not progesterone level rises to the values in sham-operated controls, 20-month-old rats ovariectomized at the age of 10 months served as an experimental model. Estrogen and progesterone receptor expression, secretion of pro- and anti-inflammatory cytokines, and arginine metabolism end-products were examined in splenic and peritoneal macrophages under basal conditions and following lipopolysaccharide (LPS) stimulation in vitro. Almost all peritoneal and a subset of splenic macrophages expressed the intracellular progesterone receptor. Ovariectomy diminished cytokine production by splenic (IL-1β) and peritoneal (TNF-α, IL-1β, IL-10) macrophages and increased the production of IL-10 by splenic and TGF-β by peritoneal cells under basal conditions. Following LPS stimulation, splenic macrophages from ovariectomized rats produced less TNF-α and more IL-10, whereas peritoneal macrophages produced less IL-1β and TGF-β than the corresponding cells from sham-operated rats. Ovariectomy diminished urea production in both subpopulations of LPS-stimulated macrophages. Although long-lasting isolated progesterone deficiency in the post-reproductive age differentially affects cytokine production in the macrophages from distinct tissue compartments, in both subpopulations, it impairs the pro-inflammatory/anti-inflammatory cytokine secretory balance.