PCOS is not solely endocrine related to higher androgen production. Inflammation is also significant.
PCOS has an immunological basis. Increased pro-inflammatory M1 macrophages and decreased anti inflammatory M2 macrophages.
This leads to fibrosis and is a significant part of obesity related inflammatory tissues changes throughout the body tissues.
How can one treat and reverse the macrophage inflammatory shift and reverse the M1/M2 ratio?
1. Melatonin reverses PCOS due to antioxidant and Nrf2 activation.
2. Vagal reflex activation stimulates the cholinergic anti-inflammatory pathway and shifts the phenotype of M1 towards M2. Acetylcholine is released into the bloodstream and binds the nicotine acetylcholine receptors in macrophages to cause this shift.
3. Because organs such as spleen, pancreas, liver and ovaries are cloistered behind blood brain barriers, one can better address the cholinergic tone within the organs by the Wim Hot breathing technique that uses hyperventilation to raise both pH and bicarbonate which directly activates acetylcholinesterase inhibition by acting on mesothelial cells.
This is entirely logical because testosterone is associated with abdominal visceral body fat while estrogen inhibits visceral body fat in favor of "pear shaped" peripheral body fat. PCOS is an estrogen producing female with elevated testosterone production. The relative increase in visceral body fat promotes inflammation that drives increased abdominal body fat and insulin resistance. Block the inflammation AND block the increased oxidative stress to broadly treat the syndrome.
Polycystic ovary syndrome: possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/macrophages
Polycystic ovary syndrome (PCOS) is a continuum of endocrine and reproductive disorders characterized by hyperandrogenism, antral follicle growth arrest and chronic inflammation. Macrophages play key role in inflammation and the balance between M1 (inflammatory) and M2 (anti-inflammatory) macrophages determines physiological/pathological outcomes. Here, we investigated if hyperandrogenism increases ovarian chemerin altering the balance of M1 and M2 macrophages and the granulosa cell death. Ovarian chemerin was up-regulated by 5α-dihydrotestosterone (DHT) in lean and overweight rats; while increased serum chemerin levels were only evident in overweight rats, suggesting that the serum chemerin may be reflective of a systemic response and associated with obesity, whereas increased ovarian chemerin expression is a localized response independent of the metabolic status. DHT altered follicle dynamics while increased the M1: M2 macrophages ratio in antral and pre-ovulatory follicles. While ovarian M1 macrophages expressing chemokine-like receptor 1 (CMKLR1) were increased, CMKLR1 + monocytes, which migrated towards chemerin-rich environment, were markedly decreased after 15 days of DHT. Androgen-induced granulosa cell apoptosis was dependent on the presence of macrophages. In humans, chemerin levels in follicular fluid, but not in serum, was higher in lean PCOS patients compared to BMI-matched controls and was associated with increased M1: M2 ratio. Our results support the concept that in PCOS, hyperandrogenemia increases chemerin expression while promotes CMKLR1 + monocytes recruitment and deregulates the immunological niche of ovaries. This study established a new immunological perspective in PCOS at the ovarian level. Hyperandrogenism is associated with up-regulation of chemerin and macrophage unbalance in the ovaries.
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