Estradiol modulates Kiss1 neuronal response to ghrelin

Autor(es)

Frazao, Renata ^{[1, 2]} ; Lemko, Heather M. Dungan ^[2] ; da Silva, Regina P. ^[1] ; Ratra, Dhirender V. ^{[3, 4]} ; Lee, Charlotte E. ^[2] ; Williams, Kevin W. ^[2] ; Zigman, Jeffrey M. ^[2] ; Elias, Carol F. ^{[3, 4, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil

^[2] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 - USA

^[3] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 - USA

^[4] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 - USA

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 306, n. 6, p. E606-E614, MAR 2014.
• Citações Web of Science: 34

Resumo

Ghrelin is a metabolic signal regulating energy homeostasis. Circulating ghrelin levels rise during starvation and fall after a meal, and therefore, ghrelin may function as a signal of negative energy balance. Ghrelin may also act as a modulator of reproductive physiology, as acute ghrelin administration suppresses gonadotropin secretion and inhibits the neuroendocrine reproductive axis. Interestingly, ghrelin's effect in female metabolism varies according to the estrogen milieu predicting an interaction between ghrelin and estrogens, likely at the hypothalamic level. Here, we show that ghrelin receptor (GHSR) and estrogen receptor-alpha (ER alpha) are coexpressed in several hypothalamic sites. Higher levels of circulating estradiol increased the expression of GHSR mRNA and the co-xpression of GHSR mRNA and ER alpha selectively in the arcuate nucleus (ARC). Subsets of preoptic and ARC Kiss1 neurons coexpressed GHSR. Increased colocalization was observed in ARC Kiss1 neurons of ovariectomized estradiol-treated (OVX + E-2; 80%) compared with ovariectomized oil-treated (OVX; 25%) mice. Acute actions of ghrelin on ARC Kiss1 neurons were also modulated by estradiol; 75 and 22% of Kiss1 neurons of OVX + E-2 and OVX mice, respectively, depolarized in response to ghrelin. Our findings indicate that ghrelin and estradiol may interact in several hypothalamic sites. In the ARC, high levels of E-2 increase GHSR mRNA expression, modifying the colocalization rate with ER alpha and Kiss1 and the proportion of Kiss1 neurons acutely responding to ghrelin. Our findings indicate that E-2 alters the responsiveness of kisspeptin neurons to metabolic signals, potentially acting as a critical player in the metabolic control of the reproductive physiology. (AU)

• Processo FAPESP: 12/12554-8 - 42nd Annual Meeting of the Society for Neuroscience - Neuroscience 2012
• Beneficiário: Renata Frazão
• Linha de fomento: Auxílio à Pesquisa - Reunião - Exterior
• Processo FAPESP: 13/00801-3 - Envolvimento dos neurônios Kiss1 na via neural através da qual o sistema circadiano regula o ciclo ovulatório
• Beneficiário: Regina Silva Paradela
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/12202-4 - Modulação das propriedades biofísicas de neurônios Kiss1 por fatores circadianos
• Beneficiário: Renata Frazão
• Linha de fomento: Auxílio à Pesquisa - Regular