Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/72259
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective |
Autor: | Ciriza, Iratxe CSIC; Carrero, Paloma CSIC; Frye, C. A.; García-Segura, Luis M. CSIC ORCID | Fecha de publicación: | 2006 | Editor: | John Wiley & Sons | Citación: | Journal of Neurobiology 66: 916-928 (2006) | Resumen: | The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration. In the nervous system, progesterone is metabolized to 5α-dihydroprogesterone (DHP) by the enzyme 5α-reductase. DHP is subsequently reduced to 3α,5α- tetrahydroprogesterone (THP) by a reversible reaction catalyzed by the enzyme 3α-hydroxysteroid dehydrogenase. In this study we have analyzed whether progesterone metabolism is involved in the neuroprotective effect of the hormone in the hilus of the hippocampus of ovariectomized rats injected with kainic acid, an experimental model of excitotoxic cell death. Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5α-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3α-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone. © 2006 Wiley Periodicals, Inc. | URI: | http://hdl.handle.net/10261/72259 | DOI: | 10.1002/neu.20293 | Identificadores: | doi: 10.1002/neu.20293 issn: 0022-3034 |
Aparece en las colecciones: | (IC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
118
checked on 21-abr-2024
WEB OF SCIENCETM
Citations
110
checked on 24-feb-2024
Page view(s)
330
checked on 24-abr-2024
Download(s)
114
checked on 24-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.