OverMachoGrande
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A Closer Look At: SHBG & Metabolic Clearance.
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OverMachoGrande
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OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
More info on lignans, S.H.B.G. and metabolic clearance.
http://books.google.com/books?id=Cg0Ne_ ... -1&f=false
and
http://www.redorbit.com/news/health/115 ... index.html
Quote from the above website: It is of interest that some lignans, including ENL and END, bind to SHBG and interfere with 5alpha-dihydrotestosterone binding.115 In HepG2 cell studies with ENL,89 significant stimulation of SHBG production was found at lower physiological concentrations but inhibition at higher. An increase of SHBG results in a lowering of the percentage of free testosterone and estradiol as well as in a reduction of both the albumin-bound and free fraction of the sex hormones. This reduces the metabolic clearance rate of the steroids and, in this way, prolongs their biological activity.Unbound SHBG interacts with a cell-membrane receptor; when steroids are then introduced, the complex may activate cellular enzymes.116,117 This means that SHBG has a potentially important role as a regulator of cell function, and the stimulatory effect of lignans on SHBG production becomes even more important.
More info on lignans, S.H.B.G. and metabolic clearance.
http://books.google.com/books?id=Cg0Ne_ ... -1&f=false
and
http://www.redorbit.com/news/health/115 ... index.html
Quote from the above website: It is of interest that some lignans, including ENL and END, bind to SHBG and interfere with 5alpha-dihydrotestosterone binding.115 In HepG2 cell studies with ENL,89 significant stimulation of SHBG production was found at lower physiological concentrations but inhibition at higher. An increase of SHBG results in a lowering of the percentage of free testosterone and estradiol as well as in a reduction of both the albumin-bound and free fraction of the sex hormones. This reduces the metabolic clearance rate of the steroids and, in this way, prolongs their biological activity.Unbound SHBG interacts with a cell-membrane receptor; when steroids are then introduced, the complex may activate cellular enzymes.116,117 This means that SHBG has a potentially important role as a regulator of cell function, and the stimulatory effect of lignans on SHBG production becomes even more important.
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
According to the below website. Ketoconazole (the active ingredient in nizoral shampoo) displaces both D.H.T. and estradiol from S.H.B.G.! Could this be the secret to M.P.B.?
http://aac.asm.org/cgi/reprint/23/2/207.pdf
Once again, breaking D.H.T. and estradiol off of S.H.B.G. is the only way you lower the levels of these hormones. The breaking of D.H.T. and estradiol away from S.H.B.G. leaves plenty of room for testosterone to bind with, which once bound, cannot be converted, thus an increase in total testosterone levels, which is what you want. Once D.H.T. and estradiol are "free" from S.H.B.G. they become excreted.
According to the below website. Ketoconazole (the active ingredient in nizoral shampoo) displaces both D.H.T. and estradiol from S.H.B.G.! Could this be the secret to M.P.B.?
http://aac.asm.org/cgi/reprint/23/2/207.pdf
Once again, breaking D.H.T. and estradiol off of S.H.B.G. is the only way you lower the levels of these hormones. The breaking of D.H.T. and estradiol away from S.H.B.G. leaves plenty of room for testosterone to bind with, which once bound, cannot be converted, thus an increase in total testosterone levels, which is what you want. Once D.H.T. and estradiol are "free" from S.H.B.G. they become excreted.
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
The control of the interaction of sex hormone-binding globulin with its receptor by steroid hormones.
D J Hryb, M S Khan, N A Romas and W Rosner.
Sex hormone-binding globulins (SHBG) is a plasma glycoprotein that binds certain steroids. It, in turn, binds to a specific receptor on cell membranes. This work was undertaken to investigate the role of steroids in the interaction of SHBG with its receptor. Because the probe for the interaction of SHBG with its receptor is 125I-SHBG, we first showed that 125I-SHBG binds [3H]dihydrotestosterone (DHT) at 4 degrees C and 37 degrees C with KD values similar to those published previously for pure radioinert SHBG. 125I-SHBG could be prevented from binding to its receptor by a variety of steroids whose relative inhibitory activity (dihydrotestosterone much greater than 2-methoxyestradiol greater than testosterone greater than estradiol much greater than methyltrienolone greater than cortisol) was almost identical to their relative ability to bind to SHBG. Because significant binding of [3H]DHT to the SHBG receptor could not be demonstrated, steroid inhibition of SHBG binding must be noncompetitive. If steroids bound to SHBG prevent binding to the SHBG receptor, then liganded SHBG should have a higher apparent KD for its receptor than unliganded SHBG. This is the case. The KD was 0.86 +/- 0.25 nM for the high affinity receptor site using liganded SHBG and 0.19 +/- 0.024 nM for unliganded SHBG. Thus, only liganded SHBG assumes a conformation that prohibits interaction with the SHBG receptor. However, when unliganded SHBG was prebound to its receptor, it retained its ability to bind [3H] DHT. The model that emerges from these observations is as follows. Unliganded SHBG can bind either steroids or receptor in a reversible reaction; SHBG bound to a steroid cannot bind to the receptor, but unliganded SHBG that first binds to the receptor can subsequently bind steroids.
The control of the interaction of sex hormone-binding globulin with its receptor by steroid hormones.
D J Hryb, M S Khan, N A Romas and W Rosner.
Sex hormone-binding globulins (SHBG) is a plasma glycoprotein that binds certain steroids. It, in turn, binds to a specific receptor on cell membranes. This work was undertaken to investigate the role of steroids in the interaction of SHBG with its receptor. Because the probe for the interaction of SHBG with its receptor is 125I-SHBG, we first showed that 125I-SHBG binds [3H]dihydrotestosterone (DHT) at 4 degrees C and 37 degrees C with KD values similar to those published previously for pure radioinert SHBG. 125I-SHBG could be prevented from binding to its receptor by a variety of steroids whose relative inhibitory activity (dihydrotestosterone much greater than 2-methoxyestradiol greater than testosterone greater than estradiol much greater than methyltrienolone greater than cortisol) was almost identical to their relative ability to bind to SHBG. Because significant binding of [3H]DHT to the SHBG receptor could not be demonstrated, steroid inhibition of SHBG binding must be noncompetitive. If steroids bound to SHBG prevent binding to the SHBG receptor, then liganded SHBG should have a higher apparent KD for its receptor than unliganded SHBG. This is the case. The KD was 0.86 +/- 0.25 nM for the high affinity receptor site using liganded SHBG and 0.19 +/- 0.024 nM for unliganded SHBG. Thus, only liganded SHBG assumes a conformation that prohibits interaction with the SHBG receptor. However, when unliganded SHBG was prebound to its receptor, it retained its ability to bind [3H] DHT. The model that emerges from these observations is as follows. Unliganded SHBG can bind either steroids or receptor in a reversible reaction; SHBG bound to a steroid cannot bind to the receptor, but unliganded SHBG that first binds to the receptor can subsequently bind steroids.
Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
I am with you Mr. E, good work, idem to Stephen. I like persons trying to find the real first cause of common alopecia, the current theory don't resolve all observed facts. Bryan is a good guy, with a very good background, but a few conservative to draft his own theory, perhaps vit. D as Farrel?
Armando
P.D. Do you remember the "sleeping guy"?
misterE said:Bryan said:I can name a couple of other people who also think "outside the box": Ernie Primeau and Stephen Foote. Should we pay attention to THEIR theories of balding?
Personally, I love Stephen Foote's theories and I strongly admire his ruthless attack on the balding process. And that is what separates him from you. He comes up with theories and shares them with us...And it seems to me, with all the "wisdom" you have, you could at least share some of that "wisdom" with us, by giving us your theories and solutions!
I am with you Mr. E, good work, idem to Stephen. I like persons trying to find the real first cause of common alopecia, the current theory don't resolve all observed facts. Bryan is a good guy, with a very good background, but a few conservative to draft his own theory, perhaps vit. D as Farrel?
Armando
P.D. Do you remember the "sleeping guy"?
purecontrol
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
Could you clerify the theory, #1 are you wanting A) less SHBG or B) just to displace the Estrogen and DHT? #2 are you wanting high or low levels of SHBG?
Could you clerify the theory, #1 are you wanting A) less SHBG or B) just to displace the Estrogen and DHT? #2 are you wanting high or low levels of SHBG?
purecontrol
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
Here is some information I would like to share with everyone to help them better understand the facts.
Sex hormone binding globulin (SHBG) is a glycoprotein possessing high affinity binding for 17 beta-hydroxysteriod hormones such as testosterone and oestradiol. It is probably synthesized in the liver, plasma concentrations being regulated by, amongst other things, androgen/oestrogen balance, thyroid hormones, insulin and dietary factors, it is involved in transport of sex steroids in plasma and its concentration is a major factor regulating their distribution between the protein-bound and free states. Its detailed role in the delivery of hormones to target tissues is not yet clear. Plasma SHBG concentrations are affected by a number of different diseases, high values being found in hyperthyroidism, hypogonadism, androgen insensitivity and hepatic cirrhosis in men. Low concentrations are found in myxoedema, hyperprolactinaemia and syndromes of excessive androgen activity. Concentrations are also affected by drugs such as androgens, oestrogens, thyroid hormones and anti-convulsants. Measurement of SHBG is useful in the evaluation of mild disorders of androgen metabolism and enables identification of those women with hirsutism who are more likely to respond to oestrogen therapy. Testosterone:SHBG ratios correlate well with both measured and calculated values of free testosterone and help to discriminate subjects with excessive androgen activity from normal individuals.
http://www.ncbi.nlm.nih.gov/pubmed/2080856
So as you can see it is well documented in what states the SHBG is highest and lowest.
When is it lowest? It is lowest when you have greater than normal levels of androgens and estrogens, and ER & AR (these are their respective receptors).
When is it highest? It is highest when you have the lower than normal levels of androgens and estrogen, and the ER & AR (once again these are the respective receptors).
So it is very valid to grow a thesis from this information and other information that SHBG will increase the activity / affinity of the androgens and or estrogens making them even more potent. Perhaps you could look at it like this, in a free state these hormones are walking the streets with no map hoping to find their desitnation. However with SHBG it is like having a taxi driver take you right to your destination for you.
So in this thinking the SHBG will make the homrone more potent.
As you can see things like diet are extremely important as well as other lifestyle choices, to where or not you have high or low SHBG levels.
From my persepective you want to keep SHBG as low as possbile, this can be accomplished through keep low insulin and glucose levels, exercise, proper sleep hygiene and more.
So you can see how to make the sex hormones less potent, next you need to know how to make sure there are less receptors for these androgens where you do not want them ie your skin, hair etc.
Here is some information I would like to share with everyone to help them better understand the facts.
Sex hormone binding globulin (SHBG) is a glycoprotein possessing high affinity binding for 17 beta-hydroxysteriod hormones such as testosterone and oestradiol. It is probably synthesized in the liver, plasma concentrations being regulated by, amongst other things, androgen/oestrogen balance, thyroid hormones, insulin and dietary factors, it is involved in transport of sex steroids in plasma and its concentration is a major factor regulating their distribution between the protein-bound and free states. Its detailed role in the delivery of hormones to target tissues is not yet clear. Plasma SHBG concentrations are affected by a number of different diseases, high values being found in hyperthyroidism, hypogonadism, androgen insensitivity and hepatic cirrhosis in men. Low concentrations are found in myxoedema, hyperprolactinaemia and syndromes of excessive androgen activity. Concentrations are also affected by drugs such as androgens, oestrogens, thyroid hormones and anti-convulsants. Measurement of SHBG is useful in the evaluation of mild disorders of androgen metabolism and enables identification of those women with hirsutism who are more likely to respond to oestrogen therapy. Testosterone:SHBG ratios correlate well with both measured and calculated values of free testosterone and help to discriminate subjects with excessive androgen activity from normal individuals.
http://www.ncbi.nlm.nih.gov/pubmed/2080856
So as you can see it is well documented in what states the SHBG is highest and lowest.
When is it lowest? It is lowest when you have greater than normal levels of androgens and estrogens, and ER & AR (these are their respective receptors).
When is it highest? It is highest when you have the lower than normal levels of androgens and estrogen, and the ER & AR (once again these are the respective receptors).
So it is very valid to grow a thesis from this information and other information that SHBG will increase the activity / affinity of the androgens and or estrogens making them even more potent. Perhaps you could look at it like this, in a free state these hormones are walking the streets with no map hoping to find their desitnation. However with SHBG it is like having a taxi driver take you right to your destination for you.
So in this thinking the SHBG will make the homrone more potent.
As you can see things like diet are extremely important as well as other lifestyle choices, to where or not you have high or low SHBG levels.
From my persepective you want to keep SHBG as low as possbile, this can be accomplished through keep low insulin and glucose levels, exercise, proper sleep hygiene and more.
So you can see how to make the sex hormones less potent, next you need to know how to make sure there are less receptors for these androgens where you do not want them ie your skin, hair etc.
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
#1 You want to displace the D.H.T. and estradiol from S.H.B.G. and replace it with testosterone. Once testosterone is bound to S.H.B.G. it cannot be converted to D.H.T. or estrogen.
#2 You want a high level of testosterone bound to S.H.B.G. If you have low S.H.B.G. you will have low testosterone levels.
purecontrol said:
#1 You want to displace the D.H.T. and estradiol from S.H.B.G. and replace it with testosterone. Once testosterone is bound to S.H.B.G. it cannot be converted to D.H.T. or estrogen.
#2 You want a high level of testosterone bound to S.H.B.G. If you have low S.H.B.G. you will have low testosterone levels.
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
Low insulin levels will increase S.H.B.G., same with exercise. S.H.B.G. is a very sensitive marker for insulin sensitivity. Both Insulin and IGF-1 are known to decrease S.H.B.G., which also is negatively associated with body weight.
Dietary Fiber increases S.H.B.G. while dietary protein and saturated fat decrease it. Vegans are known to have 13% higher S.H.B.G. bound testosterone and 9% lower IGF-1 levels compared to people eating the rich western diet.*
S.H.B.G. is a good thing if testosterone is bound to it. But can also be a bad thing if D.H.T. or estradiol is bound to it.
Once again, S.H.B.G. prolongs the half-life of hormones. So which hormones do you to be prolonged; estrogen? D.H.T.? No. You want testosterone to be prolonged!
*Allen NE. Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men. Br J Cancer. 2000 Jul;83(1):95-7.
purecontrol said:
Low insulin levels will increase S.H.B.G., same with exercise. S.H.B.G. is a very sensitive marker for insulin sensitivity. Both Insulin and IGF-1 are known to decrease S.H.B.G., which also is negatively associated with body weight.
Dietary Fiber increases S.H.B.G. while dietary protein and saturated fat decrease it. Vegans are known to have 13% higher S.H.B.G. bound testosterone and 9% lower IGF-1 levels compared to people eating the rich western diet.*
S.H.B.G. is a good thing if testosterone is bound to it. But can also be a bad thing if D.H.T. or estradiol is bound to it.
Once again, S.H.B.G. prolongs the half-life of hormones. So which hormones do you to be prolonged; estrogen? D.H.T.? No. You want testosterone to be prolonged!
*Allen NE. Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men. Br J Cancer. 2000 Jul;83(1):95-7.
purecontrol
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
You do understand the higher the SHBG the more potent that androgens and estrogen right?
Vegan men and women have extremely low testosterone leves and the body compensates by increase SHBG to increase receport affinity.
How are you proposing to control what hormones attatch to the SHBG?
misterE said:
You do understand the higher the SHBG the more potent that androgens and estrogen right?
Vegan men and women have extremely low testosterone leves and the body compensates by increase SHBG to increase receport affinity.
How are you proposing to control what hormones attatch to the SHBG?
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
Yes, that is why you want testosterone bound to S.H.B.G. instead of estradiol or D.H.T.
S.H.B.G. would be increasing the potency of testosterone instead of estradiol or D.H.T.
I don't think so. Meat eaters have higher IGF-1 levels than vegans...this is true. But IGF-1 decreases S.H.B.G. which then allows testosterone to convert...in other words, IGF-1 decreases testosterone and increases D.H.T. and/or estradiol. Vegans have low IGF-1 so therefore their S.H.B.G. has more "integrity". There isn't as much IGF-1 in vegans to promotes testosterone loss. S.H.B.G. acts to preserve testosterone, the more S.H.B.G. the more testosterone. "Free" testosterone or testosterone that is not bound to S.H.B.G. isn't going to be testosterone for much longer because it will be converted.
Resveratrol, nettle root extract, plant lignans, zinc, beta sitosterol, equol, phytoestrogens and even ketoconazole, all prevent D.H.T. and estradiol from binding to S.H.B.G. thus increasing their metabolic clearance rate.
purecontrol said:
Yes, that is why you want testosterone bound to S.H.B.G. instead of estradiol or D.H.T.
S.H.B.G. would be increasing the potency of testosterone instead of estradiol or D.H.T.
purecontrol said:
I don't think so. Meat eaters have higher IGF-1 levels than vegans...this is true. But IGF-1 decreases S.H.B.G. which then allows testosterone to convert...in other words, IGF-1 decreases testosterone and increases D.H.T. and/or estradiol. Vegans have low IGF-1 so therefore their S.H.B.G. has more "integrity". There isn't as much IGF-1 in vegans to promotes testosterone loss. S.H.B.G. acts to preserve testosterone, the more S.H.B.G. the more testosterone. "Free" testosterone or testosterone that is not bound to S.H.B.G. isn't going to be testosterone for much longer because it will be converted.
purecontrol said:
Resveratrol, nettle root extract, plant lignans, zinc, beta sitosterol, equol, phytoestrogens and even ketoconazole, all prevent D.H.T. and estradiol from binding to S.H.B.G. thus increasing their metabolic clearance rate.
purecontrol
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
Where are these studies? How are they stopping the estrogen and dht from binding to the SHBG?
[/quote]
Where are these studies? How are they stopping the estrogen and dht from binding to the SHBG?
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
The studies are out there, I've posted a few in this thread all ready...from what I recall, beta-sitosterol has a very very high affinity to S.H.B.G.
They have a similar molecular structure to estradiol and dihydrotestosterone, hence reveratrol, sitosterol, enterolactone, so what happens is, since it has a similar structure, it is able to bind to the estrogen or androgen receptor binding site found on S.H.B.G.
If D.H.T. and estradiol are all ready bound, these substances can "knock off" D.H.T. and estradiol from S.H.B.G. which then leaves more room for "free" testosterone to bind. Remember, only "free" testosterone can enter the sebaceous glands and only then does it convert to D.H.T.
purecontrol said:
The studies are out there, I've posted a few in this thread all ready...from what I recall, beta-sitosterol has a very very high affinity to S.H.B.G.
They have a similar molecular structure to estradiol and dihydrotestosterone, hence reveratrol, sitosterol, enterolactone, so what happens is, since it has a similar structure, it is able to bind to the estrogen or androgen receptor binding site found on S.H.B.G.
If D.H.T. and estradiol are all ready bound, these substances can "knock off" D.H.T. and estradiol from S.H.B.G. which then leaves more room for "free" testosterone to bind. Remember, only "free" testosterone can enter the sebaceous glands and only then does it convert to D.H.T.
Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
This study has been around for a while.
How do you explain that INCREASING IGF-1 promotes hair growth?
EDIT: http://www.ncbi.nlm.nih.gov/pubmed/1756 ... dinalpos=4
forgot the link, LOL.
You post interesting articles, mrE; but I'm not sure if you draw the correct conclutions from reading them. These are very complicated biochemical experiments, intended for peer reveiws by specialists and researchers, I know I certainly don't know quite how to interprent them.
This study has been around for a while.
How do you explain that INCREASING IGF-1 promotes hair growth?
EDIT: http://www.ncbi.nlm.nih.gov/pubmed/1756 ... dinalpos=4
forgot the link, LOL.
You post interesting articles, mrE; but I'm not sure if you draw the correct conclutions from reading them. These are very complicated biochemical experiments, intended for peer reveiws by specialists and researchers, I know I certainly don't know quite how to interprent them.
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
Yes. Testosterone is a prohormone. The only way for testosterone to be called “testosterone†is if it is bound to S.H.B.G.
Todd said:
Yes. Testosterone is a prohormone. The only way for testosterone to be called “testosterone†is if it is bound to S.H.B.G.
OverMachoGrande
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Re: A Closer Look At: S.H.B.G. & Metabolic Clearance.
I can't explain how increasing IGF-1 would promote hair growth, because IGF-1 (along with insulin) is shown to inhibit the production of S.H.B.G. (Kaaks and Lukanova, 2001; Cordain et al 2003). S.H.B.G. is an important regulator of plasma sex hormones and a sensitive marker of insulin resistance (gates et al, 1996). Low S.H.B.G. levels are tied to increased risk of type 2 diabetes, cancer, cardio vascular disease and mortality (Gates et al, 1996)!
Todd said:
I can't explain how increasing IGF-1 would promote hair growth, because IGF-1 (along with insulin) is shown to inhibit the production of S.H.B.G. (Kaaks and Lukanova, 2001; Cordain et al 2003). S.H.B.G. is an important regulator of plasma sex hormones and a sensitive marker of insulin resistance (gates et al, 1996). Low S.H.B.G. levels are tied to increased risk of type 2 diabetes, cancer, cardio vascular disease and mortality (Gates et al, 1996)!
