Oestrogen and progestins differently prevent glutamate toxicity in cortical neurons depending on prior hormonal exposure via the induction of neural nitric oxide synthase.
Sex steroids are important for 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. The effect of a 24h pre-treatment with 17beta-estradiol or 17beta-estradiol plus progesterone or medroxyprogesterone acetate on the toxic action of l-glutamate was used to test the experimental hypothesis. Pre-exposure to either steroid combinations turned in enhanced cell survival. Instead, addition of sex steroids together with l-glutamate, in the absence of a pre-exposure had no protective effect. Pre-treatment with the steroid combinations resulted in increased neural NOS expression and activity and blockade of NOS abolished the cytoprotective effects of steroids. These results suggest that 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.
Mannella
Paolo
P
Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Pisa, 56100, Italy. p.mannella@obgyn.med.unipi.it
Sanchez
Angel Matias
AM
Giretti
Maria Silvia
MS
Genazzani
Andrea Riccardo
AR
Simoncini
Tommaso
T
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D019610:Cytoprotection / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism; D011372:Progestins / Q000494:pharmacology*; D051381:Rats
D004967:Estrogens; D011372:Progestins; D018698:Glutamic Acid; D017258:Medroxyprogesterone Acetate; D019001:Nitric Oxide Synthase