30-11-2022, 08:20 PM
Hi Breastnexus, I want to share some information I've been researching on PCOS and how it relates to a specific enzyme called 11beta-HSD1.
So basically: "The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts cortisone to cortisol and participates in the regulation of glucocorticoid levels in tissues."
https://pubmed.ncbi.nlm.nih.gov/30877174/
I shared some interesting insights in September with my good friend Sweets (info below) on cortisol and PCOS. So I've come to understand PCOS green lights more cortisol and androgens production, that's bad news pcos sufferers, one glaring obstacle is now dealing with insulin resistance (e.g
weight gain followed by androgen production).
Focusing on one aspect of PCOS which is the 11β-HSD1 enzyme and came up with an Herbal solution of EGCG (Epigallocatechine-3-gallate)…as you would find in green tea extract, or a stand alone supplement in itself. Btw, EGCG inhibits androgens too. I'll attach the literature following this post. In the study using EGCG 3.749 mg dried tea leaves per ml were used. You gotta make your green tea extract have the highest EGCG percentage. Don't mistake EGCG for the polyphenols or Catechins (which are important) in Green tea extracts. I've seen EGCG as high 70%, it's listed on the supplemental facts label each supplement bottle.
Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome
Abstract
Objective: To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity.
Design: Cross-sectional study.
Subjects: A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR.
Results: Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11beta-HSD1 mRNA. The subgroups LP and OC had increased 11beta-HSD1 and 11beta-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on 11 beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH.
Conclusion: Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.
Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1
Jan Hintzpeter et al. PLoS One. 2014.
Free PMC article
Show details
Full text links
Cite
Abstract
The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor. There is strong evidence for an important aetiological role of 11β-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11β-HSD1 activity with selective inhibitors is being pursued as a new therapeutic approach for the treatment of the metabolic syndrome. Since tea has been associated with health benefits for thousands of years, we sought to elucidate the active principle in tea with regard to diabetes type 2 prevention. Several teas and tea specific polyphenolic compounds were tested for their possible inhibition of cortisone reduction with human liver microsomes and purified human 11β-HSD1. Indeed we found that tea extracts inhibited 11β-HSD1 mediated cortisone reduction, where green tea exhibited the highest inhibitory potency with an IC50 value of 3.749 mg dried tea leaves per ml. Consequently, major polyphenolic compounds from green tea, in particular catechins, were tested with the same systems. (-)-Epigallocatechin gallate (EGCG) revealed the highest inhibition of 11β-HSD1 activity (reduction: IC50 = 57.99 µM; oxidation: IC50 = 131.2 µM). Detailed kinetic studies indicate a direct competition mode of EGCG, with substrate and/or cofactor binding. Inhibition constants of EGCG on cortisone reduction were Ki = 22.68 µM for microsomes and Ki = 18.74 µM for purified 11β-HSD1. In silico docking studies support the view that EGCG binds directly to the active site of 11β-HSD1 by forming a hydrogen bond with Lys187 of the catalytic triad. Our study is the first to provide evidence that the health benefits of green tea and its polyphenolic compounds may be attributed to an inhibition of the cortisol producing enzyme 11β-HSD1.
So basically: "The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts cortisone to cortisol and participates in the regulation of glucocorticoid levels in tissues."
https://pubmed.ncbi.nlm.nih.gov/30877174/
I shared some interesting insights in September with my good friend Sweets (info below) on cortisol and PCOS. So I've come to understand PCOS green lights more cortisol and androgens production, that's bad news pcos sufferers, one glaring obstacle is now dealing with insulin resistance (e.g
weight gain followed by androgen production).
Focusing on one aspect of PCOS which is the 11β-HSD1 enzyme and came up with an Herbal solution of EGCG (Epigallocatechine-3-gallate)…as you would find in green tea extract, or a stand alone supplement in itself. Btw, EGCG inhibits androgens too. I'll attach the literature following this post. In the study using EGCG 3.749 mg dried tea leaves per ml were used. You gotta make your green tea extract have the highest EGCG percentage. Don't mistake EGCG for the polyphenols or Catechins (which are important) in Green tea extracts. I've seen EGCG as high 70%, it's listed on the supplemental facts label each supplement bottle.
(27-09-2022, 03:42 AM)Lotus Wrote: Hi Sweets,
But seeing you describe depression, anxiety, trouble sleeping and having pcos makes me suspect cortisol related issues mixed with pcos. Turns out androgens, insulin, cortisol play havoc on pcos. High cortisol levels can mimic pcos symptoms too. Don't let the title of the science article throw off, of you read the entire article the talk about lean subjects versus obese subjects, so there's differences to productions rates and metabolic rates. The main point being is how cortisol could be the main culprit behind your pcos, ance, sleep disturbance, weight gain, fatigue, etc...this of course is just my observation, fwiw.
Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates
"The changes in 5alpha-R, 11beta-HSD1, and 20alpha/beta-HSD enzyme activities observed in PCOS may contribute to the increased production rates of cortisol and androgens, supporting the concept of a widespread dysregulation of steroid metabolism."
https://pubmed.ncbi.nlm.nih.gov/14671189/
Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome
Abstract
Objective: To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity.
Design: Cross-sectional study.
Subjects: A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR.
Results: Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11beta-HSD1 mRNA. The subgroups LP and OC had increased 11beta-HSD1 and 11beta-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on 11 beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH.
Conclusion: Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.
Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1
Jan Hintzpeter et al. PLoS One. 2014.
Free PMC article
Show details
Full text links
Cite
Abstract
The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor. There is strong evidence for an important aetiological role of 11β-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11β-HSD1 activity with selective inhibitors is being pursued as a new therapeutic approach for the treatment of the metabolic syndrome. Since tea has been associated with health benefits for thousands of years, we sought to elucidate the active principle in tea with regard to diabetes type 2 prevention. Several teas and tea specific polyphenolic compounds were tested for their possible inhibition of cortisone reduction with human liver microsomes and purified human 11β-HSD1. Indeed we found that tea extracts inhibited 11β-HSD1 mediated cortisone reduction, where green tea exhibited the highest inhibitory potency with an IC50 value of 3.749 mg dried tea leaves per ml. Consequently, major polyphenolic compounds from green tea, in particular catechins, were tested with the same systems. (-)-Epigallocatechin gallate (EGCG) revealed the highest inhibition of 11β-HSD1 activity (reduction: IC50 = 57.99 µM; oxidation: IC50 = 131.2 µM). Detailed kinetic studies indicate a direct competition mode of EGCG, with substrate and/or cofactor binding. Inhibition constants of EGCG on cortisone reduction were Ki = 22.68 µM for microsomes and Ki = 18.74 µM for purified 11β-HSD1. In silico docking studies support the view that EGCG binds directly to the active site of 11β-HSD1 by forming a hydrogen bond with Lys187 of the catalytic triad. Our study is the first to provide evidence that the health benefits of green tea and its polyphenolic compounds may be attributed to an inhibition of the cortisol producing enzyme 11β-HSD1.