Some women with PCOS have other signs of inflammation (as written in one of my former blogs)., one being Lupus.
Association of estrogen receptor alpha gene polymorphisms with cytokine genes expression in systemic lupus erythematosus
Abstract
AIM:
To analyze the association of estrogen receptor alpha (OR alpha) gene polymorphisms with cytokine genes expression in patients with systemic lupus erythematosus (SLE) and controls.
METHODS:
Genomic DNA was extracted and polymorphisms of XbaI, Ukrainian (XX, Xx, or xx genotype) and PvuII (PP, Pp, or pp) in intron 1 of OR alpha gene were detected by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. The messenger RNA (mRNA) levels of interleukin (IL)-10, IL-4, interferon (IFN)-gamma, and IL-2 were assessed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR).
RESULTS:
In patients with SLE with PpXx genotype, IL-10 and IL-4 mRNA expression was higher (P < 0.001 and P = 0.013, respectively), while in patients with SLE with Ppxx genotype IFN-gamma and IL-2 mRNA expression was lower than in controls (P < 0.001). There was no significant difference in mRNA expression of 4 cytokines among controls with various genotypes.
CONCLUSION:
OR alpha gene polymorphism may be associated with the expression of IL-10, IL-4, IL-2, and IFN-gamma in patients with SLE.
Estrogen Receptor Signaling and Its Relationship to Cytokines in Systemic Lupus Erythematosus
E. Kassi1,2 and P. Moutsatsou1
1Department of Biological Chemistry, Medical School, University of Athens, 75 M. Asias, Goudi, 11527 Athens, Greece
2Laboratory of Clinical Biochemistry, “Attikon” University General Hospital, 1 Rimini, Haidari, 12462 Athens, Greece
Received 15 January 2010; Revised 18 March 2010; Accepted 31 March 2010
Academic Editor: Brian Poole
Copyright © 2010 E. Kassi and P. Moutsatsou. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Dysregulation of cytokines is among the main abnormalities in Systemic Lupus Erythematosus (SLE). However, although, estrogens, which are known to be involved in lupus disease, influence cytokine production, the underlying molecular mechanisms remain poorly defined. Recent evidence demonstrates the presence of estrogen receptor in various cell types of the immune system, while divergent effects of estrogens on the cytokine regulation are thought to be implicated. In this paper, we provide an overview of the current knowledge as to how estrogen-induced modulation of cytokine production in SLE is mediated by the estrogen receptor while simultaneously clarifying various aspects of estrogen receptor signaling in this disease.
...
Although estrogens have been proposed as obvious candidates to explain this sexual dimorphism [17], measurement of plasma estradiol levels did not reveal significant differences between normal women and women with SLE; nevertheless, abnormal levels of estrogenic metabolites have been identified in the latter. These metabolites include 2-hydroxy- and 16-hydroxyestrone and their derivatives produced by the enzymatic oxidation of estrogen. Additionally, pregnancy is frequently associated with flares of the disease in SLE patients [17]. Of note, pregnancy can disturb the balance in favor of the highly feminizing 16-hydroxy metabolites, thus predisposing to SLE, while exercise or consuming specific foods that inhibit the 16-hydroxylase can have opposite effects [18].
...SLE is characterized by numerous immune system disturbances including alterations in cytokine regulation. Estrogens are known modulators of immune system functions, influence cytokine production and are involved in the lupus disease process. Accumulating evidence on the molecular and cellular actions of estrogens via the estrogen receptor subtypes ER
and ER
Recent evidence indicates a role of estrogens in mitochondrial function in immune cells along with cytokine regulation, while the existence of mitochondrial ER in human cells has been associated with stimulation of mitochondrial encoded enzymes."
http://www.hindawi.com/journals/jbb/2010/317452/
"BACKGROUND: Recent research shows that polycystic ovary syndrome (PCOS) may have an association with low-grade chronic inflammation, and that PCOS may induce an increase in serum interleukin-18 (IL-18) levels. [2010]"
"This article reviews the literature available on the role of T helper cytokines and IL-1, IL-11 [?]
, LIF [?]
http://www.ihop-net.org/UniPub/iHOP/gs/89488.html
We aimed to study if the changes observed in the insulin sensitivity of PCOS patients during treatment with oral contraceptives or metformin associate changes in the serum inflammatory markers interleukin-6
Fast Facts
An imbalance in thyroid and adrenal hormones, testosterone, the estrogen’s (estrone, estradiol, estriol), and progesterone can affect the immune system.
Our chemical environment (xenoestrogens) and nutrition are both contributing factors to hormone imbalance
“A hormone is a chemical substance which is produced in one location of the body and travels to another to convey, create, or generate a response”.
Dr. Jesse Stoff (M.D.).
It’s also important to note that no hormone works in isolation from other hormones; they all function within a complex, subtle web of interconnectedness. Reference: Dr. John Lee Many hormones have an effect on the immune system, disease and each other.
Thyroid Hormone Imbalance and the Immune System
“Thyroid hormone stimulates the activity of Natural Killer (NK) cells [cells in the immune system].” Dr. Jesse Stoff
What nutritional element does the thyroid need to function? Iodine.
Janice Wittenberg, RN states that “Iodine in particular is important to the production of the thyroid hormone. Low to sub-clinical [not measurable through testing] thyroid function is very common. Soils in the mid-west and areas along the St. Lawrence have the lowest iodine concentrations and largest number of thyroid related problems in the world."
“Estrogen inhibits thyroid hormone activity and thus exacerbates thyroid deficiency. In contrast, progesterone, cortisol, and testosterone are thyroid allies.” Dr. John Lee
The most common symptoms (there are many) of a low functioning thyroid are fatigue and intolerance to cold according to Dr. James Balch.
Adrenal Glands and the Immune System
Janice Wittenberg R.N. in her book, "The Rebellious Body", comments on adrenal glands by saying that they can, as a result of stress and nutritional deficiencies, produce hormones that inhibit the production of prostaglandins that interfere with immune response.
These hormones also deplete thymus [immune system] function. The thymus gland is responsible for training an immune system cell grouping called T cells. She says pantothenic acid is particularly important in strengthening the adrenals among other things. The hormone produced in excess is cortisol.
Testosterone, Estrogen & Progesterone - hormone balance
The hormones testosterone, progesterone and estrogen can be found in both men and women, just in different amounts.
Estrogen is getting a lot of attention and rightly so as it’s a powerful hormone and found everywhere. Testosterone and progesterone balance its effects.
According to Dr. John Lee, MD, estrogen is a word that encompasses a class of three hormones; estrone, estradiol and estriol. It’s not one hormone. Of the estrogens, estradiol is the strongest and estriol is the weakest.
Estrogens come from different places. First, they are produced by the body in both men and women. Second, plants produce compounds with estrogen like qualities. They’re called phytoestrogens.
Xenoestrogens refer to the third kind which are environmental compounds (usually petrochemicals) and can be found everywhere – like in pesticides, meats or plastics.
The fourth kind are chemical estrogens made by pharmaceutical companies for use in things like hormone replacement therapy. Dr. Peter J. D’Adamo states that chemical estrogens are based on estradiol, the strongest, while phytoestrogens or plant based estrogens, are typically high in estriol, the weakest.
Estrogen Dominance Upsets Hormone Balance
Estrogen dominance is a term that can apply to both women and men. It’s described by Dr. John Lee as “a condition where a woman can have deficient, normal, or excessive estrogen but has little or no progesterone to balance its effects in the body.”
He further states, “ A key to hormone balance is the knowledge that when estrogen becomes the dominant hormone and progesterone is deficient, the estrogen becomes toxic to the body…”
Progesterone is the “antidote” to the harmful effects of estrogen creating greater hormone balance. While a correct hormone balance between estrogen and progesterone is particularly important to women, it’s also important to men and just used in smaller amounts.
Testosterone for men also helps protect against the harmful effects of estrogen and the hormone imbalances it causes.
"The Hormone Replacement Debacle" by John Lee M.D.
"xProstate Cancer Survival, Testosterone & Estrogen" by John Lee M.D.
Hormone Imbalance Causes 5 yr. Olds to Grow Breasts & Pubic Hair
Hormone imbalance is not a small problem. The following is one example of what estrogens can do:
A couple of years ago, a clinic in Montana had several 5 year old girl patients who were developing breasts and exhibiting other signs of physical maturity way beyond their age.
After investigating the situation, the clinic director discovered that all the girls' families bought milk from the same dairy. It was then discovered that the advanced physical development these girls were experiencing were due to the hormones used in the dairy products.
This caused a hormone imbalance because the estrogen levels were too high. This is not isolated to Montana. This is a growing problem in this country and could be one of the causes of overweight children and adults as well.
Some of the things estrogen, testosterone and progesterone do with reference to the immune system and disease are as follows:
Estrogen, Progesterone and the Immune System
Dr. Willian Hrushesky believes that natural killer cell activity and interleukin 2, both powerful immune system components, are compromised by estrogen dominance and promoted by adequate progesterone. His opinions were presented in the Journal of Women’s Health.
Dr. John Morrow, PhD and Dr. David Isenberg PhD say that estrogen has been shown to decrease the size of the thymus [depresses immune system] and to cause a reduction in the level of thymic hormone in the blood.
They also say it has been shown that the level of thymic hormone is markedly decreased in the blood of women who are either post-menopausal or who have had their ovaries removed and are undergoing estrogen therapy.
Estrogen, Progesterone and Cancer
Dr. David Zava tested estrogen and progesterone levels in breast tissue specimens from several thousand women who had undergone breast cancer surgery. “Almost universally, they revealed a deficiency in progesterone relative to estrogen.”
John’s Hopkins published a study that showed that “the breast cancer incidence was 5.4 time greater in women with low progesterone than in women who had good progesterone levels…when the incidence of all types of cancer was looked at, they found that the incidence was 10 fold higher in women with low progesterone levels compared to women with good progesterone levels.”
“Estrogens in general tend to promote cell division, particularly in hormone sensitive tissue…” says Dr. John Lee. He also says that on a “gene” level, two genes figure prominently, Bcl-2 and p53. Bcl-2 production promotes cell proliferation (cancer). It is stimulated by estrogen. On the other hand, activation of gene p53 activated by progesterone, inhibits Bcl-2 shutting down cell proliferation.
Dr. Lauren Sompayrac states, “One indication of the importance of p53 (see above) is that this anti-oncogene is not activated in a large proportion of human tumors”. P53 is activated by progesterone according to Dr. John Lee.
Hormone Imbalance and Autoimmune Disease
Drs. .Morrow and Isenberg also state, “There is little doubt that oral contraceptives, especially those with moderate or high doses of estrogen, can exacerbate or even induce a relapse of quiescent [latent, dormant] autoimmune disease.
” In addition they explain, “There are some reports of high estrogen levels in both females and males with this disease [lupus].
Male patients with lupus have also been shown to have lower levels of the male sex hormone testosterone.” Dr. John Lee also states that recent studies have shown that “women who use hormone replacement therapy containing estrogen are more likely to get lupus.”
Dr. John Lee says that “ Women are afflicted with autoimmune diseases at a much higher rate than men, which is a good clue that female hormone balance in involved in some way. …The onset of autoimmune disorders is often in middle age, when estrogen dominance becomes common.”
His conclusions are that estrogen dominance may have a hand in triggering the problem and thus correcting the estrogen dominance leads to gradual correction of the problem.
Or, since progesterone is the main precursor of corticosteroids, and in progesterone deficient women, restoration of normal progesterone levels may enhance normal corticosteroid production, thus suppressing the autoimmune attack.
http://immunedisorders.homestead.com/Hormones.html
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