Molecular mechanisms involved in the regulation of hypothalamic neuronal development by estradiol

CAMBIASSO, M.J.

Ribero Preto

Simposio; Recent advances in the study of the Integrative Physiology with emphasis on the neuroendocrine control of energy metabolism and body fluid homeostasis; 2012

Department of Physiology, School of Medicine of Ribeirao Preto (USP)

17-b-estradiol (E2) has multiple and important physiological effects on several tissues and cellular phenotypes. The actions of E2 on developing brain are generally permanent and range from establishment of sex differences to the regulation of process related to growth, differentiation and survival of neurons and glial cells. Some of these processes are related to neuronal plasticity, synaptic organization, neuritogenesis, axonal and dendritic growth. E2 also impacts on cellular physiology by modulating calcium balance, immediate-early-gene expression and kinase activity. The specific mechanisms of E2 action permanently impacting the brain are regionally and sex specific and often involve neuronal/glial cross-talk interactions. In our laboratory (Córdoba-Argentina), we have demonstrated that at embryonic age of 16, before the masculinizing effects of gonadal steroids, E2 induces axonal growth only in hypothalamic neurons of male rat embryos. Moreover, this neuritogenic effect is mediated by a mechanism that does not involve the classical intracellular pathway of nuclear estrogen receptor (ER), instead this axogenic effect depends on a membrane-initiated mechanism involving the activation of Ca2+-PKC and MAPK/ERK/CREB signaling pathways. Recently, we have found a truncated form of the ERa localized in membrane fractions of hypothalamic tissue from E16 embryos and on the cell-surface of E2-stimulated hypothalamic neurons. We have proposed that this truncated ERa located at the membrane participates in the activation of MAPKs to induce axonal growth.