Impact of sex steroids on neuroinflammatory processes and experimental multiple sclerosis

Synthetic and natural estrogens as well as progestins modulate neuronal development and activity. Neurons and glia are endowed with high-affinity steroid receptors. Besides regulating brain physiology, both steroids conciliate neuroprotection against toxicity and neurodegeneration. The majority of data derive from in vitro studies, although more recently, animal models have proven the efficaciousness of steroids as neuroprotective factors. Indications for a safeguarding role also emerge from first clinical trials. Gender-specific prevalence of degenerative disorders might be associated with the loss of hormonal activity or steroid malfunctions. Our studies and evidence from the literature support the view that steroids attenuate neuroinflammation by reducing the pro-inflammatory property of astrocytes. This effect appears variable depending on the brain region and toxic condition. Both hormones can individually mediate protection, but they are more effective in cooperation. A second research line, using an animal model for multiple sclerosis, provides evidence that steroids achieve remyelination after demyelination. The underlying cellular mechanisms involve interactions with astroglia, insulin-like growth factor-1 responses, and the recruitment of oligodendrocytes. (C) 2009 Elsevier Inc. All rights reserved.