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  • Obestatin increased GnRH mRNA expression in the

    2021-09-23

    Obestatin increased GnRH mRNA expression in the POA, being the main place of GnRH synthesis (Goodman, 2015). Simultaneously, obestatin also caused a decrease in the GnRH mRNA expression in ME, without affecting the level of this peptide mRNA in AHA. A lack of differences observed in the mRNA level in AHA is probably related to the fact that AHA contains mainly neurites in which mRNA synthesis does not occur. However, in literature an AG-1024 information about the AG-1024 of mRNA to the distal parts of neurons, such as dendrites, axons and nerve endings can be found. It has been suggested that intracellular mRNA transport may affect the local synthesis of proteins in nerve endings, which may play an important role in the functioning of the axon and the nerve endings themselves (Herman and Tomaszewska-Zaremba, 2010; Kaplan et al., 2004). This theory seems to be highly probable because in the earlier studies it was shown the existence of transport granules containing, except of mature mRNA, also ribosomes and elongation factors. It is believed that these granules may form a fully functional translational unit (Herman and Tomaszewska-Zaremba, 2010). Therefore, it can be assumed that the presence of such translational unit at various sites of the nerve cell allows these cells to make a much faster and more efficient response to changes in neuronal activity (Kaplan et al., 2004). Central obestatin infusion evoked the restraining of IR GnRH material in nerve terminals of the ME. This observation can be interpreted as diminished release of GnRH to the hypophyseal portal system. Such an interpretation can be supported by the results of our preliminary studies, where the decrease in the GnRH-receptor mRNA expression and the accumulation of IR LH material in the pituitary gonadotrophs of obestatin-infused sheep has been observed. As a consequence, diminished release of LH into the blood circulation was noted, which is consistent with the lower LH plasma concentrations in obestatin-infused sheep (Szlis et al., 2016, Szlis et al., 2015). Taking into account the above information we can hypothesize that obestatin can act as a metabolic signal inhibiting the GnRH release from the nerve terminals in the ME and thereby attenuate the gonadotrophic axis activity. To the best of our knowledge, the results of earlier studies performed on mice and baboon revealed that obestatin did not affect LH and FSH release. However, the analysis of gonadotrophins expression/release was performed on primary pituitary cell cultures which, to a large extent, may explain the difference in the achieved results (Luque et al., 2014). Thus, our in vivo study for the first time shows that exogenous obestatin can modulate sheep gonadotrophic axis activity acting at the hypothalamus level. As mentioned earlier, it is probable that obestatin, like other peripheral hormones involved in the regulation of the organism energy status (leptin and ghrelin), indirectly changes the activity of GnRH neurons. One of the possible mediators of the obestatin action could be the KNDy neurons subpopulation located in the ARC nucleus and its main effector hormone – Kiss. The results obtained in the present study indicate that intracelebroventricular obestatin infusion changed the KNDy mRNA expression in sheep ARC. An increase in Kiss mRNA and decrease in PDyn mRNA expressions were noticed while level of NKB transcript has not been changed after obestatin treatment. On the other hand, the immunohistochemical analysis of Kiss expression showed marked decrease or even absence of IR Kiss material in ARC perikarya and nerve fibers in ME in sheep after obestatin infusion. The similar discrepancy between the level of mRNA and the protein level of the studied hormone is often observed (Szlis et al., 2018; Wójcik-Gładysz et al., 2018). It is possible that obestatin inhibits the expression of Kiss protein by acting at the post-transcriptional regulation level e.g., microRNA regulation, but this issue, however, requires further thorough research. Therefore it is possible that Kiss may be a ‘metabolic mediator’ of the obestatin inhibitory actions on the gonadotrophic axis activity.