Análisis de la contribución de p53 en el control metabólico de la pubertad y las neuronas Kiss1

Abstract

Puberty is a physiological process that is determinant to reach reproductive capacityin adult organisms, controlled by Kiss1 neurons of the arcuate nucleus, asa key regulatory factor of the hypothalamic-pituitary-gonadal axis. Currently, thereare numerous unknowns about its molecular regulation and associated alterationsthat entail serious health consequences. In this regard, p53 has been identified asone of the main regulatory components of a gene network whose hypothalamicexpression increases during puberty. Therefore, the aim is to analyse the possiblerole of p53 in the neuroendocrine regulation of puberty. For this purpose, p53 hypothalamicexpression profiles during postnatal/pubertal maturation and changesthat occur under conditions of undernutrition and obesity were defined in femalerats, and in vivo inhibition of p53 was performed by intracerebroventricular pharmacologicaltreatment with pifithrin-α p-nitro. The results obtained showed thatthe acetylated and phosphorylated isoforms of p53 might be relevant for the controlof pubertal onset. Furthermore, effect of the inhibitor showed that absence ofp53 could cause a delay in phenotypic characteristics of puberty. In conclusion,this project suggests that p53 has functions related to the control of pubertal process,possibly acting on Kiss1.