Hormones and auto-immune diseases

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Hormones and auto-immune diseases

Postby bromley » Wed Feb 22, 2006 5:27 am

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Hormones and MS

Postby Shayk » Thu Feb 23, 2006 7:57 pm

Thanks Bromley— The article states:
Oestrogen turns up the adaptive immune system, improving the ability to fight off infection but making it more susceptible to auto-immune disease. In males, testosterone appears to suppress it.

I must say from my reading about hormones I am of the impression testosterone may reduce the susceptibility of being diagnosed with MS and estrogen definitely seems to be anti-inflammatory. I don’t know anything though about the innate/adaptive immune systems and have no earthly idea why the adaptive immune response in women would make them more susceptible to auto-immune diseases. I’m curious to learn from the auto-immune experts why that would be the case. It’s going to take a lot to convince me that MS is auto-immune. :wink:

That estrogen is anti-inflammatory and neurprotective is reviewed in part in this abstract, From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens . Another abstract highlights the role of mitochondria in neuroprotection afforded by estrogen. Mitochondria play a central role in estrogen-induced neuroprotection Note:
The discovery that 17alpha-estradiol, an isomer of E2, is equally as cytoprotective as E2 yet is >200-fold less active as a hormone, has permitted development of novel, more potent analogs where cytoprotection is independent of hormonal potency…….
This therapeutic strategy is germane not only to sudden mitochondrial failure in acute circumstances, such as during a stroke or myocardial infarction, but also to gradual mitochondrial dysfunction associated with chronic degenerative disorders such as AD, PD and HD.

Mitochondrial dysfunction, as already posted elsewhere, may be real relevant to MS too. Mitochondrial Dysfunction as a Cause of Axonal Degeneration MS

Enough about estrogen. One of these days Bromley I’ll have a post that says “This One’s For You”…..I really do appreciate your posting info you think I’d be interested in. I am.

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Re: Hormones and auto-immune diseases

Postby CaliReader » Thu Sep 26, 2013 11:03 am

I found a 2013 article that further establishes neuroprotection benefit from sex hormones. I'm posting it here because of the useful information in this thread from 2006. I really appreciate the wealth of knowledge and depth of insight in the conversation that has been happening on thisisms over the years.

Here is the excerpt from the recent article re hormones and ms, available in full text from pub med central.

Front Neuroendocrinol. Author manuscript; available in PMC 2013 April 4.
Published in final edited form as:
Front Neuroendocrinol. 2012 January; 33(1): 105–115.
Published online 2011 December 24. doi: 10.1016/j.yfrne.2011.12.001
PMCID: PMC3616506
NIHMSID: NIHMS346478
Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration
Rory D. Spence and Rhonda R. Voskuhl*

With estrogen’s ability to provide protection in a number of CNS disease models, much research has been focused on the mitochondria as a target of estrogens actions. Treatments with estrogens have a direct neuroprotective effect on mitochondria [16,55,95,96,97]. Estrogens have been shown to increase aerobic glycolysis, respiratory efficiency, ATP generation, Ca2+ load tolerance and act as an antioxidant defense [17]. Furthermore, estrogens can alter pro and anti-apoptotic molecules that act on the mitochondria. For instance, estrogen can increase anti-apoptotic markers, bcl-2 and bcl-xl, while decreasing the pro-apoptotic marker bax in animal models of AD [96]. Estrogen’s antioxidant properties also allow it to protect against reactive oxygen species from the mitochondria [119]. It is important to note that the timing of estrogen administration is critical to ensure estrogens protective outcome as noted in the healthy cell bias of estrogen action hypothesis. If estrogens are administered too late in the disease they are not protective [17,94,124,156].

****

15. Conclusion
Currently, MS treatments have a primary focus on reducing inflammation. Given that MS is both an inflammatory and neurodegenerative disease, there is a need for neuroprotective treatments if one aims to fully halt the disease [86]. Estrogens and androgens both have the potential to play neuroprotective roles in the treatment of MS. EAE studies with various estrogen and androgen treatments led to clinical disease protection, as well as protection from CNS inflammation, axonal loss, as well as demyelination. ER? ligand treatment was able to completely abrogate both early and late stages of disease. However, it is unlikely ER? ligand treatment could be used long term or in high doses since breast and ovarian cancers are mediated via ER? in humans [12,90]. ER? ligand and estriol treatments remain promising candidates for MS since they have the potential to be much safer due to either no, or relatively low, binding to ER? respectively [60,63,62,155]. In the EAE model, ER? ligand was able to ameliorate late signs of clinical disease while providing neuroprotection even in the presence of CNS inflammation [23,141]. Recent evidence suggests that ER? ligand may not only prevent demyelination, but also promote remyelination [23]. However, since ER? ligand is does not prevent CNS inflammation, it would theoretically need to be given in combination with an anti-inflammatory agent in MS [32]. Androgen treatment remains a candidate for male MS patients. While some anti-inflammatory effects of testosterone have been shown in EAE, direct neuroprotective effects have not been addressed. It remains unclear whether the protective effect of testosterone might be due to its conversion to estrogen in the CNS.
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