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dc.contributor.authorMcArthur, Sen_US
dc.contributor.authorGillies, GEen_US
dc.date.accessioned2017-01-11T17:08:20Z
dc.date.available2011-11-10en_US
dc.date.issued2011en_US
dc.date.submitted2016-11-17T10:41:25.568Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/18497
dc.description.abstractThe nigrostriatal dopaminergic (NSDA) pathway degenerates in Parkinson's disease (PD), which occurs with approximately twice the incidence in men than women. Studies of the influence of systemic estrogens in females suggest sex hormones contribute to these differences. In this review we analyze the evidence revealing great complexity in the response of the healthy and injured NSDA system to hormonal influences, and emphasize the importance of centrally generated estrogens. At physiological levels, circulating estrogen (in females) or estrogen precursors (testosterone in males, aromatized to estrogen centrally) have negligible effects on dopaminergic neuron survival in experimental PD, but can modify striatal dopamine levels via actions on the activity or adaptive responses of surviving cells. However, these effects are sexually dimorphic. In females, estradiol promotes adaptive responses in the partially injured NSDA pathway, preserving striatal dopamine, whereas in males gonadal steroids and exogenous estradiol have a negligible or even suppressive effect, effectively exacerbating dopamine loss. On balance, the different effects of gonadal factors in males and females contribute to sex differences in experimental PD. Fundamental sex differences in brain organization, including the sexually dimorphic networks regulating NSDA activity are likely to underpin these responses. In contrast, estrogen generated locally appears to preserve striatal dopamine in both sexes. The available data therefore highlight the need to understand the biological basis of sex-specific responses of the NSDA system to peripheral hormones, so as to realize the potential for sex-specific, hormone-based therapies in PD. Furthermore, they suggest that targeting central steroid generation could be equally effective in preserving striatal dopamine in both sexes. Clarification of the relative roles of peripheral and central sex steroid hormones is thus an important challenge for future studies.en_US
dc.format.extent82 - ?en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofFront Endocrinol (Lausanne)en_US
dc.rightsThis is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.
dc.subjectParkinson’s diseaseen_US
dc.subjectcentral vs. gonadal steroidsen_US
dc.subjectestrogenen_US
dc.subjectnigrostriatal pathwayen_US
dc.subjectsexen_US
dc.titlePeripheral vs. Central Sex Steroid Hormones in Experimental Parkinson's Disease.en_US
dc.typeArticle
dc.rights.holder© 2011 McArthur and Gillies.
dc.identifier.doi10.3389/fendo.2011.00082en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/22649388en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
pubs.volume2en_US
dcterms.dateAccepted2011-11-10en_US


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