Sex steroid differently prevent glutamate toxicity in neuroblastoma cells depending on prior hormonal exposure

P. MANNELLA; A.M. SANCHEZ; M.S. GIRETTI; A. CARUSO; S. GARIBALDI; M.I. FLAMINI; XD. FU; C. BALDACCI; T. SIMONCINI; A.R.GENAZZANI

February 28-March 2, Florence, Italy

Congreso; 13th World Congress of Gynecological Endocrinology.; 2008

Sex steroids have been recognized as potent regulators of the brain function. The lack of these molecules is responsible of significant alterations at the neural cell level. Aim of this paper was to study the role of sex steroid deprivation and sex steroid pretreatment on neuroblastoma cell survival in presence or absence of a toxic stimulus such as the glutamate. Furthermore, the effects of sex steroid re-administrations were studied on sex steroid deprived or pretreated cells. Neuroblastoma cells were pretreated with estrogen plus progesterone or deprived of steroids for 24 hours and then treated with with l-glutamate, a toxic stimulus, plus 17b-estradiol, progesterone and medroxyprogesterone acetate. The efficacy of these molecules on preventing cell death was assessed by cytosurvival tests. 17 b-estradiol, progesterone and medroxyprogesterone acetate either alone or in co-administration promoted neural cell survival. These effects were dependent upon prior exposure of the cells to the estrogen plus progesterone. In fact, in steroid deprived cells, such protective effects were partially abolished or even reversed. We then hypothesized that the mechanism by which sex steroids promoted survival in neural cells, could be dependent on activation of nitric oxide synthase. Pharmacological blockade of nitric oxide synthase by the use a potent inhibitor reduced the ability of neuroblastoma cells to respond to the steroid-dependent prosurvival effects, even when pretreated with sex steroids. These data confirmed that sex steroid treatment induces divergent effects when administrated after a long period of steroid deprivation or to cells continuously exposed to sex steroid.