Endogenous estrogen formation is neuroprotective in model of cerebellar ataxia.
The expression of aromatase, the enzyme that transforms testosterone into estradiol, was analyzed by reverse transcriptase polymerase chain reaction in the inferior olive of adult male rats. The expression of this messenger in the inferior olive suggests that this brain area may be able to synthesize estradiol. The neuroprotective role of estradiol in the inferior olive was then assessed in a model of cerebellar ataxia, achieved by the ip administration of 3-acetylpyridine (3-AP). In a first experiment, male Wistar rats were orchidectomized to diminish the plasmatic levels of testosterone, the direct precursor of estradiol. Immediately after castration, animals were implanted with a silicone tube that was either empty or filled with estradiol. One week later, animals were injected with 3-AP. Estradiol treatment resulted in a significant reduction in neuronal death in the olive. In a second experiment, animals were treated with fadrozole, an aromatase inhibitor, to assess the role of endogenous estradiol formation in neuroprotection. The results show that the inhibition of aromatase activity, and therefore the decrease in endogenous estrogen formation, increases the death in inferior olive. In conclusion, this study indicates that the inferior olive is a steroidogenic tissue and that olivary neurons are protected by exogenous and endogenous estradiol.
Sierra
Amanda
A
Instituto Cajal, C.S.I.C., Madrid, Spain.
Azcoitia
Iñigo
I
Garcia-Segura
Luis
L
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002524:Cerebellar Ataxia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004958:Estradiol / Q000096:biosynthesis* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009847:Olivary Nucleus / Q000201:enzymology / Q000473:pathology / Q000502:physiology; D011725:Pyridines; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011725:Pyridines; D012333:RNA, Messenger; C010835:3-acetylpyridine; D004958:Estradiol; D001141:Aromatase; D017316:Fadrozole