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

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 PGF2 alpha remains unclear. To clarify this issue, the participation of alpha 1-, alpha 2- and beta-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 PGF2 alpha 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 alpha 1-, alpha 2- and beta-ARs antagonists. In the CON and E.coli groups, NA increased endometrial PGFS and CBR1 protein abundances and PGF2 alpha 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 PGF2 alpha release were higher, while PGFS protein abundance was lower than in the CON group. In the latter group, the antagonists of alpha 1A-, alpha 1D-, alpha 2B- and alpha 2C-ARs isoforms and beta 2-ARs subtype decreased NA-stimulated PGFS protein abundances, compared to NA action alone. In the E.coli group, this effect on PGFS abundances evoked alpha 1D-, alpha 2C-, beta 1- and beta 2-ARs antagonists with NA. Antagonists of alpha 1B-, alpha 2B-, beta 1- and beta 2-ARs in the CON group and antagonists of alpha 1B-, alpha 1D-, alpha 2A-, alpha 2C-, beta 1- and beta 2-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, alpha 1D-, alpha 2C- and beta 2-ARs antagonists with NA reduced PGF2 alpha secretion in both the CON and E.coli groups. Such effect on PGF2 alpha release was also exerted in the E.coli group by alpha 1B-, alpha 2A- and beta 1-ARs antagonists with NA. Summarizing, in the porcine inflamed endometrium, NA increases PGFS protein abundance via alpha 1D-, alpha 2C- and beta(1, 2)-ARs, and CBR1 protein abundance and PGF2 alpha release by alpha 1(B, D)-, alpha 2(A, C) and beta(1, 2)-ARs. The obtained findings suggest that, in an indirect manner, NA may affect the PGF2 alpha-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.