Estrogen and progestins differently prevent glutamate toxicity in cortical neurons depending on prior hormonal exposure via the induction of neural nitric oxide synthase.

P. MANNELLA; A.M. SANCHEZ; M.S. GIRETTI; A.R. GENAZZANI

March 5-8, Venezia, Italy

Congreso; 13th World Congress on Human Reproduction.; 2009

Sex steroids are important for the brain function and protection. However, growing evidence suggests that these actions might depend on the timing of exposure to steroids. We have studied the effects of steroid administration on the survival of neural cells and we have partially characterized the possible mechanisms. After neural cells have been previously exposed or not to 24 hours pre-treatment with 17 beta-estradiol or 17 beta-estradiol plus progesterone or medroxyprogesterone acetate, the neurotoxic agent, l-glutamate has been added. The pre-exposure to any of the steroid combinations turned in enhanced cell survival. Instead, the addition of sex steroids together with l-glutamate, in absence of a pre-exposure, did not protect cortical neurons. The pre-treatment with steroid combinations resulted in increased neural NOS expression and activity and the block of NOS abolished the cytoprotective effects of steroids. These results suggest NOS induction might be involved in sex steroid induced neuroprotection. Furthermore, these data supports the hypothesis that prolonged and continued exposure to oestrogen and progesterone, leading to changes in gene expression, is necessary to obtain neuroprotection induced by sex steroids.