Interaction of Estradiol and Notch/Neurogenin3 Signaling Pathway on Hypothalamic Neurons

SCERBO, M.J.; RUIZ-PALMERO, I.; ACAZ-FONSECA, E.; GARCIA-SEGURA, L.M.; CAMBIASSO, M.J.; AREVALO, M.A.

Huerta Grande

Congreso; XXVI Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias (SAN); 2011

Sociedad Argentina de Investigacion en Neurociencias (SAN)

Sexually segregated hypothalamic neurons respond differentially to the hormonal environment before the masculinizing actions of gonadal steroids. At the embryonic stage 16, 17â-estradiol (E2) induces axonal growth only in male hypothalamic neurons. Recent studies have shown that E2 and Notch signaling converge to control neuritogenesis in hippocamapal neurons. Activation of Notch is associated with an enhancement of the expression of the transcription factors Hes1 and Hes5, which negatively regulate the proneural gene Ngn3 that is involved in neuritic growth. Using real time PCR we have detected that E14 hypothalamic neurons express Ngn3 in a sexually dimorphic pattern: female neuronal cultures had significantly higher Ngn3 mRNA levels than males. E2 significantly increased Ngn3 mRNA in males but not in females. This effect was blocked by the ERá/â-mediated transcription antagonist ICI. In addition, male neuronal cultures had significantly higher Hes1 mRNA levels than females and E2 significantly reduced Hes1 mRNA levels in males, but not in females. The effect of E2 on Hes1 was also blocked by ICI. These results suggest that E2 and Notch signaling pathways interact in hypothalamic neurons with a sexually dimorphic pattern even before the organizational effect of gonadal steroids. Sexually segregated hypothalamic neurons respond differentially to the hormonal environment before the masculinizing actions of gonadal steroids. At the embryonic stage 16, 17â-estradiol (E2) induces axonal growth only in male hypothalamic neurons. Recent studies have shown that E2 and Notch signaling converge to control neuritogenesis in hippocamapal neurons. Activation of Notch is associated with an enhancement of the expression of the transcription factors Hes1 and Hes5, which negatively regulate the proneural gene Ngn3 that is involved in neuritic growth. Using qPCR we have detected that E14 hypothalamic neurons express Ngn3 in a sexually dimorphic pattern: female neuronal cultures had significantly higher Ngn3 mRNA levels than males. E2 significantly increased Ngn3 mRNA in males but not in females. This effect was blocked by the ERá/â-mediated transcription antagonist ICI. In addition, male neuronal cultures had significantly higher Hes1 mRNA levels than females and E2 significantly reduced Hes1 mRNA levels in males, but not in females. The effect of E2 on Hes1 was also blocked by ICI. These results suggest that E2 and Notch signaling pathways interact in hypothalamic neurons with a sexually dimorphic pattern even before the organizational effect of gonadal steroids