Noradrenaline and adrenoreceptors regulate prostaglandin F2α formation in endometrium after experimentally-induced inflammation in the pig

Abstract

Abstract Endometritis is the most common pathology in animals. However, in the context of an inflamed endometrium, alterations occur in the production of prostaglandins (PGs) and the noradrenergic innervation of the uterus, although the precise relationship between noradrenaline (NA), adrenoreceptors (ARs), and the output of PGF2α remains unclear. To clarify this issue, the participation of α1-, α2- and β-ARs in NA-influenced the PGF synthase (PGFS) and PG 9-ketoreductase/carbonyl reductase (CBR1) protein abundances in the porcine inflamed endometrium, and the secretion of PGF2α from the tissue were determined. E.coli suspension ( E.coli group) or saline (CON group) was injected into the uterine horns. After eight days, severe acute endometritis was diagnosed in the E.coli group. Endometrial explants were treated with NA and/or α1-, α2- and β-ARs antagonists. In the CON and E.coli groups, NA increased endometrial PGFS and CBR1 protein abundances and PGF2α secretion, compared to the control values (obtained from an endometrium that had not undergone any in vitro treatment). In the E.coli group, NA-stimulated CBR1 protein abundance and PGF2α release were higher, while PGFS protein abundance was lower than in the CON group. In the latter group, the antagonists of α1A-, α1D-, α2B- and α2C-ARs isoforms and β2-ARs subtype decreased NA-stimulated PGFS protein abundances, compared to NA action alone. In the E.coli group, this effect on PGFS abundances evoked α1D-, α2C-, β1- and β2-ARs antagonists with NA. Antagonists of α1B-, α2B-, β1- and β2-ARs in the CON group and antagonists of α1B-, α1D-, α2A-, α2C-, β1- and β2-ARs in the E.coli group eliminated a rise in the NA-stimulated CBR1 abundance of protein versus the NA influence alone. In comparison to NA effect alone, α1D-, α2C- and β2-ARs antagonists with NA reduced PGF2α secretion in both the CON and E.coli groups. Such effect on PGF2α release was also exerted in the E.coli group by α1B-, α2A- and β1-ARs antagonists with NA. Summarizing, in the porcine inflamed endometrium, NA increases PGFS protein abundance via α1D-, α2C- and β(1, 2)-ARs, and CBR1 protein abundance and PGF2α release by α1(B, D)-, α2(A, C) and β(1, 2)-ARs. The obtained findings suggest that, in an indirect manner, NA may affect the PGF2α-regulated processes by influencing its production and secretion. The results could offer new targets for drugs to regulate inflammation and improve uterine and ovarian functions.