Many of us have heard that women, who choose the birth
control pill (containing two sex hormones estrogen and progestin, a form of
progesterone) as a preventative method for contraception, are at a higher risk
of blood clots and strokes.
So I thought it was very interesting to read a study that
concluded estrogen could help the brain after a traumatic injury, such as a
stroke. The two active, major biological
forms of estrogen are estrone (E1) and estradiol (E2), which fluctuate during a
woman’s menstrual cycle (follicular and luteal phases). There
is a third form, estriol (E3), which is the main pregnancy estrogen. E1 is mainly from adrenal glands.
E2 is mainly in ovaries and testes, with small amounts in adrenal glands and
some peripheral tissues.
Astrocytic (glial cell in the central nervous system) E2
works as an anti-inflammatory signal via alteration of cytokine signaling,
where nonantibody proteins are released as part of the body’s immune system
response. When E2 is induced, it can help protect the brain
from harmful effects of prolonged neuroinflammation including neural damage and
endangering central pathways.
After a brain injury, neuroinflammation could have positive
and negative effects, with a temporal post-incident connotation. Short-term,
inflammation of the brain recruits cells to help in recovery but long-term
inflammation can be harmful and result in death of brain cells. This apoptosis
can lead to memory loss and lack of movement.
Researchers found that zebra finches, both female and male,
had an increase amount of inflammatory proteins at damaged sites within the
brain when estrogen production was prevented. The E2 that is helpful with inflammation was
produced within the brain by astrocytic cells close to the point of injury, not
gonadal.
Future studies can manipulate the forms of therapy available
to patients and induce higher E2 levels to help with the prolonged inflammation
and prevent the long-term affects of inflammation.
References
Estrogens, Estrone (E1) and
Estradiol (E2), 2014. Mayo MedicalLaboratories. Mayo
Clinic. Available from: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84230
Pedersen AL, Nelson LH,
Saldanha CJ. 2014. Estradiol, synthesized by reactive glia, is a potent
anti-inflammatory in the injured vertebrate brain. Neuroscience. The Online
Abstract Submission and Invitation System.
Brookshire B. 2014. After
injury, estrogen may shield the brain. News in Brief. Neuroscience. Available from: https://www.sciencenews.org/article/after-injury-estrogen-may-shield-brain
This is neat especially considering how often we see those commercials looking to sue drug companies after complications with birth control pills. It seems like with birth control and with many things, too much of something is never good. Endogenous estrogen at its present levels has good anti-inflammatory affects. Once you supplement with exogenous hormones, birth control, they is a tipping point where now a woman is at increased risk for blood clots. It would be cool for future studies to look at the difference between estrogen that is allowed to circulate throughout the body and those that only have local affects and its influence on inflammation. There is also an older article out there that suggest that Testosterone may have anti-inflammatory effects as well. They based this off the fact that it is women who are more predisposed inflammatory diseases and the biggest difference between males and females is that males have an abundance of Testosterone (Pergola et al. 2011). Data suggested that Testosterone lowered Phospholipase D activity which is an important enzyme in the inflammation cascade (Pergola et al. 2011). Does this mean that Testosterone could also help with neuro-inflammation? Overall it is amazing how these hormones can have multiple effects throughout the body!
ReplyDeleteReference:
Pergola C, Rogge A, Dodt G, Northoff H, Weinigel C, Barz D, Radmark O, Sautebin L, Werz O. 2011 Testosterone suppresses phospholipase D, causing sex differences in leukotriene biosynthesis in human monocytes. The FASEB Journal [Internet]. DOI: 10.1096/fj.11-182758. Available from: http://www.fasebj.org/content/25/10/3377
Indeed! Homeostasis is a tricky beast and E2 seems especially two-faced. Apparently E2 is also categorized as a carcinogen. Back in 2003, Dr. Hari Bhat et al. implanted pellets of E2 in hamsters that were susceptible to estrogen-induced kidney cancer, leading nearly all recipients to develop cancer within seven months. The researchers deduced that E2 promotes cell proliferation and produces oxidative stress when metabolized by the cell. The production of oxygen free radicals (which is often related to chronic inflammation) seems quite contrary to its use as an anti-inflammatory... Either way, I suppose it would be beneficial to take anti-oxidants in good measure if you're on an E2 regimen!
DeleteReference:
2003. Estrogen's Role in Cancer. In Vivo [Internet]. [cited 2014 Dec 1]. Available from: http://www.cumc.columbia.edu/publications/in-vivo/Vol2_Iss10_may26_03/.
Wow! I did not know that estrogen could act on brain. Can it pass through blood-brain barrier when it is secreted by ovaries or adrenal gland? Also, do you know if testosterone involves the similar mechanism of the action?
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