The effect of orexin A on CYP17A1 and CYP19A3 expression and on oestradiol, oestrone and testosterone secretion in the porcine uterus during early pregnancy and the oestrous cycle

- Orexin A affects uterine steroidogenesis during early pregnancy and the cycle.
- Orexin A effect on uterine steroidogenesis is dependent on the stage of pregnancy.
- Orexin A may affect pregnancy establishment via uterine steroidogenesis modulation.

Orexin A (OXA) is a hypothalamic neuropeptide known for its role in the regulation of food intake and arousal. It is also considered as a link between energy homeostasis and reproduction. Nevertheless, very little is known on the role of this peptide in the uterus. The objective of this study was to investigate OXA effect on oestradiol (E2), oestrone (E1), and testosterone (T) secretion by porcine endometrial and myometrial explants and gene expression of key steroidogenic enzymes involved in steroid production, namely cytochrome P450c17 (CYP17A1) and cytochrome P450 aromatase (CYP19A3), on days 10-11, 12 to 13, 15 to 16 and 27 to 28 of pregnancy and on days 10-11 of the cycle. In endometrium, OXA increased E1 secretion on days 10-11 and 15 to 27 of gestation, and T release on days 12-13. A decrease in E2, E1 and T secretion was noted on days 27-28, 12 to 13 and 10 to 11 of gestation, respectively. OXA enhanced CYP17A1 and CYP19A3 expression on days 15-28 of pregnancy, whereas decreased their expression on days 10-13. In the myometrium, OXA increased E1 secretion on days 10-16 of pregnancy, whereas inhibited the release of E2 and T on days 10-11. CYP17A1 and CYP19A3 genes expression was enhanced on days 27-28 and 12 to 13 of pregnancy, respectively. The expression of both genes was suppressed on days 10-11 and 15 to 16 of pregnancy (P < 0.05). Our findings suggest that OXA, via its influence on steroidogenesis, may play a regulatory role in the uterus.