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 Marta Kiezun, Nina Smolinska * , Kamil Dobrzyn, Karol Szeszko, Edyta Rytelewska, Tadeusz Kaminski Department of Animal Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A,10-718, Olsztyn, Poland article info Article history: Received 23 September 2016 Received in revised form 20 November 2016 Accepted 26 November 2016 Available online 28 November 2016 Keywords: Orexin A Uterus Pregnancy The estrous cycle Pig Steroids abstract 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 (E 2 ), oestrone (E 1 ), 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 10e11, 12 to 13,15 to 16 and 27 to 28 of pregnancy and on days 10e11 of the cycle. In endometrium, OXA increased E 1 secretion on days 10e11 and 15 to 27 of gestation, and Trelease on days 12e13. A decrease in E 2 ,E 1 and T secretion was noted on days 27e28, 12 to 13 and 10 to 11 of gestation, respectively. OXA enhanced CYP17A1 and CYP19A3 expression on days 15e28 of pregnancy, whereas decreased their expression on days 10e13. In the myometrium, OXA increased E 1 secretion on days 10e16 of pregnancy, whereas inhibited the release of E 2 and T on days 10e11. CYP17A1 and CYP19A3 genes expression was enhanced on days 27e28 and 12 to 13 of pregnancy, respectively. The expression of both genes was suppressed on days 10e11 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. © 2016 Elsevier Inc. All rights reserved. 1. Introduction Steroid hormones acts as main regulators of the cyclic changes within the female reproductive system, as well as in the processes involved in the establishment and maintenance of pregnancy. Recent studies using the pig model have indicated that the uterus is an important steroidogenic organ producing oestrogens and an- drogens de novo, in both, early pregnant and cyclic females [1e4]. Also the expression of key steroidogenic enzymes responsible for the production of oestrogens - oestradiol (E 2 ) and oestrone (E 1 ) as well as testosterone (T), namely CYP17A1 and CYP19A3 was noted in the porcine uterus during early pregnancy and the oestrous cycle [5e7]. One may conclude that the uterine production of steroids may supplement the amount of this hormones produced by the porcine embryos. It is also hypothesised that the uterine-derived steroids may be an alternative source of signals for pregnancy recognition and maintenance as well as for the initiation of im- plantation [1,8]. Although the reproductive success is largely dependent on the female's nutritional status, very little is known on the role of metabolic factors in the regulation of uterine secretory functions, for example steroidogenesis. Orexins are postulated to be a part of a common endocrine system, which controls both, metabolism and reproduction. Orexin A (OXA) and orexin B (OXB), also known as hypocretins 1 and 2, are hypothalamic neuropeptides derived through proteolytic cleavage from a common 130-amino acid precursor molecule, prepro-orexin (PPO). The OXA and OXB consist of 33- and 28-amino acids, respectively. Their biological actions are mediated by two distinct, * Corresponding author. E-mail addresses: marta.kiezun@uwm.edu.pl (M. Kiezun), nina.smolinska@ uwm.edu.pl (N. Smolinska), kamil.dobrzyn@uwm.edu.pl (K. Dobrzyn), karol. szeszko@uwm.edu.pl (K. Szeszko), edyta.rytelewska@wp.pl (E. Rytelewska), tkam@uwm.edu.pl (T. Kaminski). Contents lists available at ScienceDirect Theriogenology journal homepage: www.theriojournal.com http://dx.doi.org/10.1016/j.theriogenology.2016.11.028 0093-691X/© 2016 Elsevier Inc. All rights reserved. Theriogenology 90 (2017) 129e140