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Obestatin may affect the GnRH/KNDy gene network in sheep hypothalamus.

The effects of obestatin on gonadotrophic axis activity in ruminants have not yet been determined. The aim of this study was to investigate the effect of intracerebroventricular infusions of obestatin on the gonadotrophin-releasing hormone (GnRH) mRNA and protein expressions as well as on KNDy mRNA and kisspeptin (Kiss) peptide expressions in peripubertal female sheep. Animals were randomly divided into two groups: the control group received intracerebroventricular infusions of the vehicle, and the obestatin group was infused with obestatin (25 μg/120 μL h-1 ). The series of four 1-h infusions per day during three consecutive days were performed. After the end of the experiment parts of sheep brains were fixed in situ for immunohistochemical analysis, while the remaining brains were frozen for Real Time qPCR analysis. Substantial changes in the activity of the GnRH and KNDy gene network were observed in obestatin-infused sheep. In those animals an increase of GnRH mRNA expression in the preoptic area, a decrease of GnRH mRNA expression in the median eminence and an increase of GnRH immunoreactivity in the median eminence were found. Moreover, changes in the KNDy mRNA expression in mediobasal hypothalamus as well as decrease Kiss expression in arcuate nucleus and median eminence were observed. It was revealed that obestatin affects the GnRH and KNDy gene network as well as Kiss at the level of mRNA and protein expression. Thereby, it can be concluded that obestatin participates in the mechanism modulating gonadotrophic axis activity at the central level in peripubertal female sheep.

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