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Role of AMPK activity in the regulation of the neuroendocrine reproductive axis

Grant number: 13/06281-1
Support type:Scholarships abroad - Research
Effective date (Start): November 01, 2013
Effective date (End): October 31, 2014
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Marcio Alberto Torsoni
Grantee:Marcio Alberto Torsoni
Host: Carol Fuzeti Elias
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Local de pesquisa : University of Michigan, United States  

Abstract

The control of the activity of the hypothalamic-pituitary-gonadal (HPG) axis is exerted by a complex network of metabolic and hormonal signals. The early activation of HPG axis promotes for example, the precocious onset of puberty, as observed in obesity. Moreover, the absence of leptin or signaling capability may also inhibit the development of puberty, lower expression of GnRH secretion of lower LH, FSH and Kisspeptin expression in the hypothalamus. In this sense, has also been described that malnutrition reduces the activity of the HPG axis and expression of GnRH and Kisspeptin. Nutritional and hormonal signals reach hypothalamic neurons reporting the energy availability. AMPK and mTOR proteins participate in this process as cellular sensor. Some studies have suggested that AMPK plays an important role in the convergence of metabolic signals toward the reproductive axis. However, the most studies have employed cell cultures model to evaluate the importance o AMPK. These studies are important to understand the interactions molecular after different stimuli, but they did not permit evaluate the importance of some hypothalamic areas for the development of puberty. Recently, studies employed animal models to investigate the role of hypothalamic nucleus premamilar ventral (PMV) in the metabolic and reproductive signals. Although these studies have advanced in the knowledge of the anatomy and physiological mechanism involved with the control of the HPG axis, other metabolic intermediates and proteins may be involved. In this sense, the present project has interest in investigate the role of AMPK protein expressed in neurons in the PMV and Kiss1 in the metabolic and reproductive axis. To address this issue will be used AMPK2-floxed that will be crossed with Kiss1-Cre recombinase mice to induce the deletion of alpha2 subunit of AMPK in Kiss1 neurons. The technique of genetic manipulation of the expression of the alpha2 subunit of AMPK by injection in bilateral PMV virus AAV-Cre recombinase in floxed-AMPK2 animals also used in this study. These animals will be evaluated with regard to sexual behavior, early puberty, hormone profile and AMPK, GnRH, kisspeptin expression in hypothalamic areas (ARC and PMV). The biochemical and moleculares changes will be evaluated in fasted conditions (fasting) and after stimulation with leptin. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TORSONI, MARCIO A.; BORGES, BEATRIZ C.; COTE, JESSICA L.; ALLEN, SUSAN J.; MAHANY, ERICA; GARCIA-GALIANO, DAVID; ELIAS, CAROL F. AMPK alpha 2 in Kiss1 Neurons Is Required for Reproductive Adaptations to Acute Metabolic Challenges in Adult Female Mice. Endocrinology, v. 157, n. 12, p. 4803-4816, DEC 2016. Web of Science Citations: 4.

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