5 alpha victim
Member
- Joined
- May 7, 2017
- Messages
- 71
This is from the Journal Of Endocrinology
http://m.joe.endocrinology-journals.org/content/212/2/111.full#ref-143
It talks about the 5AR type one, two and the three enyzme and the SRD5a1 and SRD5a2 genes that encode the enzymes. More specifically it's about 5α-Reduced glucocorticoids. Before finding this I did not even know that we had
5α-reduced metabolites of corticosterone as I have never seen it discussed on any of the forums.
Points from the Abstract that caught me eye:
"With these proposals in mind, careful attention must be paid to the possible adverse metabolic effects of 5α-reductase inhibitors, drugs that are commonly administered long term for the treatment of benign prostatic hyperplasia"
"5α-Reduced glucocorticoids (GCs) are formed when one of the two isozymes of 5α-reductase"
"However, recent findings suggest that 5α-reduced metabolites of corticosterone have dissociated actions on GC receptors (GRs) in vivo and in vitro and are thus potential candidates for safer anti-inflammatory steroids"
"5α-Dihydro- and 5α-tetrahydro-corticosterone can bind with GRs, but interest in these compounds had been limited"
"However, a greater understanding of the signalling mechanisms has revealed that transactivation represents only one mode of signalling via the GR and recently the abilities of 5α-reduced GCs to suppress inflammation have been demonstrated in vitro and in vivo"
"Thus, the balance of parent GC and its 5α-reduced metabolite may critically affect the profile of GR signalling"
"5α-Reduction of GCs is up-regulated in liver in metabolic disease and may represent a pathway that protects from both GC-induced fuel dyshomeostasis and concomitant inflammatory insult"
"Therefore, 5α-reduced steroids provide hope for drug development, but may also act as biomarkers of the inflammatory status of the liver in metabolic disease"
From the conclusion paragraph at the end:
"A further avenue of interest in 5α-reduced GCs relates to the common pharmacological inhibition of 5αRs in clinical practice. 5α-Reductase inhibitors are used to treat benign prostate hyperplasia, a disease afflicting over half of elderly men. Although unlicensed, these drugs are also used to treat women with PCOS. It is possible that these patients will develop an imbalance in parent and 5α-reduced metabolites, leaving them susceptible to adverse metabolic effects and inflammatory changes, effects more marked with dutasteride, a new dual 5αR inhibitor. To date, there have not been any comprehensive metabolic studies in patients on these drugs".
Also I found this that talks about the specific 5a reduced metabolites of glucocorticoid (that we may want to consided getting tested for and or trying to increase/supplement). The source focuses on the effects that these metabolites may have on inflammation"
Anti-inflammatory mechanisms of 5α-reduced glucocorticoids: potential dissociated steroids
"In conclusion, 5α-reduced glucocorticoid metabolites exhibit anti-inflammatory properties in macrophages. The mechanisms of actions of the metabolites differ, but both suppress inflammatory kinase pathways. Thus 5α-reduced glucocorticoid metabolites have potential as ‘dissociated’ anti-inflammatory steroid therapy"
I'm not sure yet what the significance of 5ar reduced glucocorticoid metabolites may have yet as far as how the potential D H T inhibitor induced long term lack of them could possibly be connected to PFS symptoms but it sure looks like an avenue to explore and research further seeing that chronic systematic inflammation and stress have been mentioned in the past as possible causes of PFS and that it makes sense that these metabolites could be involved.
The first source mentions what we already know about Glucorticoids and stess:
"Glucocorticoids (GCs) are steroid hormones synthesised in the adrenal cortex, which exert a plethora of effects in the body, ranging from modulation of metabolism and suppression of inflammation to regulation of stress responses and neuronal function"
This catches my eye for obvious reasons. We know that Cortisol is a Glucocorticoid produced by the Adrenal glands and that issues with the Adrenals and Cortisol have long been implicated as a potential big piece to the PFS puzzle. It's been suggested in the past that sudden changes in Cortisol levels during the initial PFS crash could be the cause or a contributing factor behind our sudden loss of muscle mass which makes sense seeing that elevated levels of Cortisol can cause muscle wasting. Our bodies not responding properly to stress seems like it's been a big focus point on this forum and I'm thinking a possible issues with inhibited 5α-Reduced glucocorticoids could possible be involved in the chronic state of stress our bodies remain in seeing that the sources I posted suggest that the 5a-Reduced metabolites of Glucocorticoids are just as or almost as important as Cortisol itself in carrying out it's intended functions.
Taking a basic look at Cortisol issues we know there is Cushing syndrome caused by two much Cortisol which can cause rapid weight gain, slender arms and legs and changes in the skin. These are things that almost all of us experience upon crashing. Than in Addison’s disease to little Cortisol causes a whole host of its own issues. Of course we would still need to look into this but a couple possibilities that come to mind involving low levels of 5a-Reduced glucocorticoids are:
1) Resulting in the Adrenal glands producing more Cortisol attempting to make up for the missing stress/inflammation reduction properties of the metabolites that we would be other wise be getting if it was not for the lack of 5AR and it's metabolites leaving us in a never ending cycle of increased Cortisol levels because of its inability to self regulate it's levels. Almost like basic negative feed back logic. The Adrenal glands would usually "see" the levels of its metabolites increase and now know to turn down production of a glucocorticoid such as Cortisol. In our case the Adrenal glands could just be "confused" because they are not seeing their down stream metabolites so they assume that it means they still have to do their thing by producing more Cortisol. It makes sense that this would happen because after doing some basic internet searching its clear that stress tells the Adrenal glands to make Cortisol and that increased Cortisol levels can cause pretty much all of our symptoms. Just a couple of examples:
"The adrenal glands produce their hormones in response to stress. They are responsible for the fight or flight response. In a stressful situation, they raise your blood pressure, transfer blood from your intestines to your extremities, increase your heart rate, suppress your immune system and increase your blood’s clotting abilit"
"Your gastrointestinal system is very sensitive to stress hormones like cortisol. You might experience nausea, heartburn, abdominal cramps, diarrhea, or constipation as a result of too many stress hormones"
"Cortisol and epinephrine can lead to jitters, a nervous stomach, feelings of panic, even paranoia"
"High levels of cortisol suppress production of serotonin, and next thing you know, you’re awash in doom and gloom"
"Consider cortisol the anti-Viagra. When stress hormones are high, libido-inducing hormones like testosterone drop and voila... nothing"
"You’re gaining weight, especially around your abdomen, even when you eat well and exercise. Cortisol tends to make you thick around the middle, even when you’re doing everything “right".
2) Contributing to systematic high levels of stress seeing that the sources I posted suggest that the metabolites of the 5a-Reduced glucocorticoids have stress and inflammation relieving properties. So assuming that the lack of these metabolites would not cause the most likely senerio of the Adrenal glands constantly make more Cortisol attempting to fix the problem we could still possible remain in a high stress and inflamed environment simply because we lack the down stream metabolites.
3) Another likely senerio is that during our initial crash our Cortisol levels went through the roof while the Adrenal glands attempted to adjust to it's missing Metabolites (causing some of the standard crash symptoms) and than later adjusted it's Cortisol levels but the lack of its 5ar Metabolites still continue to leave us unbalenced.
Maybe we could do our own study and try to have labs done testing for these 5ar reduced Metabolites and compare the results to controls. This may just end up coming down to needing to replace all of the 5ar Metabolites that are low. Alleopreg corrects the mental side effects while maybe 5ar Metabolities of the Adrenal glands may correct let's say digestion issues.
What do you guys think
http://m.joe.endocrinology-journals.org/content/212/2/111.full#ref-143
It talks about the 5AR type one, two and the three enyzme and the SRD5a1 and SRD5a2 genes that encode the enzymes. More specifically it's about 5α-Reduced glucocorticoids. Before finding this I did not even know that we had
5α-reduced metabolites of corticosterone as I have never seen it discussed on any of the forums.
Points from the Abstract that caught me eye:
"With these proposals in mind, careful attention must be paid to the possible adverse metabolic effects of 5α-reductase inhibitors, drugs that are commonly administered long term for the treatment of benign prostatic hyperplasia"
"5α-Reduced glucocorticoids (GCs) are formed when one of the two isozymes of 5α-reductase"
"However, recent findings suggest that 5α-reduced metabolites of corticosterone have dissociated actions on GC receptors (GRs) in vivo and in vitro and are thus potential candidates for safer anti-inflammatory steroids"
"5α-Dihydro- and 5α-tetrahydro-corticosterone can bind with GRs, but interest in these compounds had been limited"
"However, a greater understanding of the signalling mechanisms has revealed that transactivation represents only one mode of signalling via the GR and recently the abilities of 5α-reduced GCs to suppress inflammation have been demonstrated in vitro and in vivo"
"Thus, the balance of parent GC and its 5α-reduced metabolite may critically affect the profile of GR signalling"
"5α-Reduction of GCs is up-regulated in liver in metabolic disease and may represent a pathway that protects from both GC-induced fuel dyshomeostasis and concomitant inflammatory insult"
"Therefore, 5α-reduced steroids provide hope for drug development, but may also act as biomarkers of the inflammatory status of the liver in metabolic disease"
From the conclusion paragraph at the end:
"A further avenue of interest in 5α-reduced GCs relates to the common pharmacological inhibition of 5αRs in clinical practice. 5α-Reductase inhibitors are used to treat benign prostate hyperplasia, a disease afflicting over half of elderly men. Although unlicensed, these drugs are also used to treat women with PCOS. It is possible that these patients will develop an imbalance in parent and 5α-reduced metabolites, leaving them susceptible to adverse metabolic effects and inflammatory changes, effects more marked with dutasteride, a new dual 5αR inhibitor. To date, there have not been any comprehensive metabolic studies in patients on these drugs".
Also I found this that talks about the specific 5a reduced metabolites of glucocorticoid (that we may want to consided getting tested for and or trying to increase/supplement). The source focuses on the effects that these metabolites may have on inflammation"
Anti-inflammatory mechanisms of 5α-reduced glucocorticoids: potential dissociated steroids
"In conclusion, 5α-reduced glucocorticoid metabolites exhibit anti-inflammatory properties in macrophages. The mechanisms of actions of the metabolites differ, but both suppress inflammatory kinase pathways. Thus 5α-reduced glucocorticoid metabolites have potential as ‘dissociated’ anti-inflammatory steroid therapy"
I'm not sure yet what the significance of 5ar reduced glucocorticoid metabolites may have yet as far as how the potential D H T inhibitor induced long term lack of them could possibly be connected to PFS symptoms but it sure looks like an avenue to explore and research further seeing that chronic systematic inflammation and stress have been mentioned in the past as possible causes of PFS and that it makes sense that these metabolites could be involved.
The first source mentions what we already know about Glucorticoids and stess:
"Glucocorticoids (GCs) are steroid hormones synthesised in the adrenal cortex, which exert a plethora of effects in the body, ranging from modulation of metabolism and suppression of inflammation to regulation of stress responses and neuronal function"
This catches my eye for obvious reasons. We know that Cortisol is a Glucocorticoid produced by the Adrenal glands and that issues with the Adrenals and Cortisol have long been implicated as a potential big piece to the PFS puzzle. It's been suggested in the past that sudden changes in Cortisol levels during the initial PFS crash could be the cause or a contributing factor behind our sudden loss of muscle mass which makes sense seeing that elevated levels of Cortisol can cause muscle wasting. Our bodies not responding properly to stress seems like it's been a big focus point on this forum and I'm thinking a possible issues with inhibited 5α-Reduced glucocorticoids could possible be involved in the chronic state of stress our bodies remain in seeing that the sources I posted suggest that the 5a-Reduced metabolites of Glucocorticoids are just as or almost as important as Cortisol itself in carrying out it's intended functions.
Taking a basic look at Cortisol issues we know there is Cushing syndrome caused by two much Cortisol which can cause rapid weight gain, slender arms and legs and changes in the skin. These are things that almost all of us experience upon crashing. Than in Addison’s disease to little Cortisol causes a whole host of its own issues. Of course we would still need to look into this but a couple possibilities that come to mind involving low levels of 5a-Reduced glucocorticoids are:
1) Resulting in the Adrenal glands producing more Cortisol attempting to make up for the missing stress/inflammation reduction properties of the metabolites that we would be other wise be getting if it was not for the lack of 5AR and it's metabolites leaving us in a never ending cycle of increased Cortisol levels because of its inability to self regulate it's levels. Almost like basic negative feed back logic. The Adrenal glands would usually "see" the levels of its metabolites increase and now know to turn down production of a glucocorticoid such as Cortisol. In our case the Adrenal glands could just be "confused" because they are not seeing their down stream metabolites so they assume that it means they still have to do their thing by producing more Cortisol. It makes sense that this would happen because after doing some basic internet searching its clear that stress tells the Adrenal glands to make Cortisol and that increased Cortisol levels can cause pretty much all of our symptoms. Just a couple of examples:
"The adrenal glands produce their hormones in response to stress. They are responsible for the fight or flight response. In a stressful situation, they raise your blood pressure, transfer blood from your intestines to your extremities, increase your heart rate, suppress your immune system and increase your blood’s clotting abilit"
"Your gastrointestinal system is very sensitive to stress hormones like cortisol. You might experience nausea, heartburn, abdominal cramps, diarrhea, or constipation as a result of too many stress hormones"
"Cortisol and epinephrine can lead to jitters, a nervous stomach, feelings of panic, even paranoia"
"High levels of cortisol suppress production of serotonin, and next thing you know, you’re awash in doom and gloom"
"Consider cortisol the anti-Viagra. When stress hormones are high, libido-inducing hormones like testosterone drop and voila... nothing"
"You’re gaining weight, especially around your abdomen, even when you eat well and exercise. Cortisol tends to make you thick around the middle, even when you’re doing everything “right".
2) Contributing to systematic high levels of stress seeing that the sources I posted suggest that the metabolites of the 5a-Reduced glucocorticoids have stress and inflammation relieving properties. So assuming that the lack of these metabolites would not cause the most likely senerio of the Adrenal glands constantly make more Cortisol attempting to fix the problem we could still possible remain in a high stress and inflamed environment simply because we lack the down stream metabolites.
3) Another likely senerio is that during our initial crash our Cortisol levels went through the roof while the Adrenal glands attempted to adjust to it's missing Metabolites (causing some of the standard crash symptoms) and than later adjusted it's Cortisol levels but the lack of its 5ar Metabolites still continue to leave us unbalenced.
Maybe we could do our own study and try to have labs done testing for these 5ar reduced Metabolites and compare the results to controls. This may just end up coming down to needing to replace all of the 5ar Metabolites that are low. Alleopreg corrects the mental side effects while maybe 5ar Metabolities of the Adrenal glands may correct let's say digestion issues.
What do you guys think
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