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  • Obestatin synthetized mainly in the gastrointestinal tract p


    Obestatin, synthetized mainly in the gastrointestinal tract, participates in the regulation of metabolic functioning at both central and peripheral levels (food intake, pancreatic activity or/and adipocytes proliferation) (Granata et al., 2008; Li et al., 2011). It is involved in the complex gut-brain neurohormonal networks, whereby hormones from the gastrointestinal tract signalize the feeling of satiety and/or hunger to the hypothalamus (Lacquaniti et al., 2011). First studies conducted on rodents shown that obestatin could act via the GPR39 receptor, but at the same time there were findings which did not confirm the obestatin affinity to this receptor (Chartrel et al., 2007; Granata et al., 2008; Gurriarán-Rodríguez et al., 2015; Lauwers et al., 2006; Tremblay et al., 2007; Van Dijck et al., 2009; Zhang, 2005). However, recent data from nuclear magnetic resonance (NMR) analysis of human obestatin structure showed that this hormone have the necessary domain required for full activation of the GPR39 (Alén et al., 2012). Also studies conducted on rats and mouse skeleton muscles clearly shown that obestatin can interact with GPR39 (Gurriarán-Rodríguez et al., 2012). In our last paper we confirmed the expression of GPR39 mRNA in sheep mediobasal hypothalamus (which includes ARC) (Szlis et al., 2018). This suggests the possibility of the GPR39 expression on KNDy neurons in ARC and its participation in the transmission of information transferred by obestatin. On the other hand, the research conducted (on pancreas isolated from human body) by Italian researchers suggests the possibility of obestatin to increase the level of mRNA for the glucagon-like peptide-1 receptor (GLP-1R) which is also expressed in the CNS (Granata et al., 2008). Because of little information, participation of GLP-1R in of obestatin signaling transduction in KN-93 and whole body still need to be clarify. To our knowledge, there is only a limited information about the obestatin participation in the modulation of the gonadotrophic axis activity. So far, obestatin expression was observed in male gonads, where it is synthesized by Leydig cells (Dun et al., 2006). In in vitro studies performed on murine, rat and porcine cells, the stimulatory effects of obestatin on the expression of both cyclic adenosine mono fosfatase (cAMP) and cell signaling protein ERK1/2 were shown. The inhibitory action of obestatin on the mitogen-activated protein kinase expression also has been observed (Mészárosová et al., 2008; Zhang, 2005). Moreover, the results of in vitro experiments demonstrated that the increase in the cAMP amount is related with cellular activation of the cAMP/protein kinase A pathway (Granata et al., 2012; Mészárosová et al., 2008). It is known that these signaling pathways are responsible for the transfer of many hormonal signals involved in the regulation of the synthesis and secretion of luteinizing hormone (LH) and folliculotrophic hormone (FSH) (Hunzicker-Dunn and Maizels, 2006; Mészárosová et al., 2008; Perrett and McArdle, 2013). Furthermore, in studies carried out on porcine granulose cells, obestatin stimulated progesterone secretion to the culture medium but did not affect the secretion of estradiol and testosterone (Mészárosová et al., 2008). Different results have been obtained in studies on the obestatin action on secretory functions of human luteal cells, where the decrease in the progesterone and prostaglandin E2 and F2α secretions into the medium after obestatin treatment has been observed (Romani et al., 2012). Obestatin expression was observed also in the cells of the rat adenophysis suggesting the possible action at the central level. However, in studies on pituitary cells isolated from mouse or baboon and also in in vivo experiments on mice it was shown that obestatin did not affect prolactin, LH and FSH releases (Luque et al., 2014).
    Materials and methods
    Discussion The results of our study indicated that exogenous obestatin, centrally administered to peripubertal ewes, may influences the GnRH mRNA and protein expression in the hypothalamus. Moreover, exogenous obestatin evoked changes in the KNDy genes expression and in the immunoreactivity of the Kiss in ARC and ME. So that, for the first time, an in vivo effect of obestatin on the activity of these neurons in animals other than rodents, namely in the ruminants, was demonstrated.