Arimidex + High Dose Nettle Root

Well the dex is going to probably work better than Rebound, by better I mean provide more complete inhibition but your basic nettle isn't going to work as well as DS standardized stuff...the flavonoid(?) that they standardized for has substantially more SHBG binding ability than the others found in nettle.

Take home message, you'll need more run of the mill nettle to do the same thing.

Posted by: Benson

Well the dex is going to probably work better than Rebound, by better I mean provide more complete inhibition but your basic nettle isn't going to work as well as DS standardized stuff...the flavonoid(?) that they standardized for has substantially more SHBG binding ability than the others found in nettle.

Take home message, you'll need more run of the mill nettle to do the same thing.

D Sade needs to get on "Bulk Activate", stat.

Posted by: Redsky

Aromatase inhibitor? Check.

SHBG competitor? Check.

I figure since I've got some Arimidex lying around and Nettle is cheap, why not? Anyone else try this?

Roids without shbg are a waste...........

Horm Metab Res. 2006 Apr;38(4):279-90.

The role of plasma-binding proteins in the cellular uptake of lipophilic vitamins and steroids.

Andreassen TK.

Department of Medical Biochemistry, University of Aarhus, Denmark.

Steroid hormones and many other lipophilic compounds are believed to enter cells solely by free diffusion through the plasma membrane. However, recent work using a megalin-deficient mouse model has identified a new endocytic pathway responsible for the delivery of steroids to renal and gonadal tissues. This review describes these new pathways for uptake of 25-hydroxy-vitamin-D3 and the gonadal sex-steroids (17beta-estradiol and testosterone) bound to vitamin D-binding protein and sex hormone-binding globulin respectively. Furthermore examples of other lipophilic molecules that enter cells by receptor-mediated pathways will be presented and the receptors responsible for their uptake described.

Mol Interv. 2005 Dec;5(6):338-40.

Few things in life are "free": cellular uptake of steroid hormones by an active transport mechanism.

Lin BC, Scanlan TS.

Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-2280, USA.

Conventional dogma holds that steroid hormones traverse cell membranes passively, owing to their lipophilic nature. The recently characterized protein megalin, however, functions as a transport protein on cell surfaces to carry steroids across the plasma membrane. Upon hydrolysis of steroid-associated binding globulins in lysosomes, free hormone is liberated and may exert its effects in the cell. Megalin-independent mechanisms of steroid uptake are likely important too, as the phenotypes of megalin-deficient mice do not completely mimic the phenotypes of androgen receptor– or estrogen receptor–null mice.

Steroid hormones participate in the regulation of normal vertebrate homeostasis, development, and reproduction. The best understood mechanism of steroid action is for these signaling molecules to enter target cells and bind to their cognate intracellular receptors that, subsequently, regulate the transcription of corresponding steroid responsive genes.

Science. STKE, 13 September 2005
Vol. 2005, Issue 301, p. tw325

Does Megalin Mediate Steroid Hormone Uptake?

Androgens and estrogens circulate through the bloodstream bound to sex hormone binding globulin (SHBG), in what has been believed to be an inactive form that prevents these small, lipophilic steroids from diffusing across the plasma membrane to activate intracellular targets (see Adams). A research group that previously showed that the low-density lipoprotein receptor-related protein megalin acts as an endocytic receptor for carrier-bound vitamins A and D has now implicated megalin in the uptake of SHBG-bound sex steroids. Hammes et al. showed that 125I-labeled SHBG was taken up and degraded by rat choriocarcinoma (BN16) cells, which express megalin, and that this was blocked by receptor-associated protein (RAP), an antagonist of ligand binding to megalin. Most circulating sex steroids are bound to carrier, and the ability of RAP to inhibit [3H]Testosterone uptake depended on the ratio of SHBG and testosterone, such that inhibition was maximal when most of the testosterone was bound, whereas RAP was ineffective when most of the testosterone was free. RAP also inhibited the uptake of SHBG-bound dihydrotestosterone (DHT) and 17ß-estradiol. Uptake of fluorescein isothiocyanate (FITC)-labeled DHT together with SHBG was confirmed with confocal immunofluorescence microscopy; moreover, DHT internalized together with SHBG activated an androgen-sensitive reporter. The phenotypes of megalin knockout mice were consistent with impaired sex-steroid signaling: Megalin—/— females exhibited vaginal blockade whereas megalin—/— males exhibited impaired descent of the testes. Further, megalin-deficient embryonic tissues were resistant to the effects of exogenous androgens. Thus, the authors conclude that megalin plays a role in the cellular uptake of carrier-bound sex steroids that is critical to the proper development of steroid-responsive tissues.

Cell. 2005 Sep 9;122(5):751-62.

Role of endocytosis in cellular uptake of sex steroids.

Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE.

Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany.

Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs.

Attached File(s)  osw.gif ( 26.24k ) Number of downloads: 12
 

Posted by: oswaldosalcedo

Roids without shbg are a waste...........
*snip*

Interesting stuff, but how does that explain the rise in free test/lbm that people get when using such a combo?

Posted by: Redsky

D Sade needs to get on "Bulk Activate", stat.

You mean something like Bulk Activate?

Posted by: eclypz

My pet theory, while completely conjecture, is that - like cortisol - shbg is necessary. But too much of it and you have a problem. Would this be an accurate or helpful statement?

My uniformed guess is that you are right E.

Like cortisol and estrogen in men, the body produces it for a reason....what we want is to optimize its levels, not eradicate it like some sort of pathogen.

Posted by: Bachovas

You mean something like Bulk Activate?

Yes, exactly.

Interesting, the NP version doesn't say anything about being a Divanil™ extract. Or did I miss it?

Posted by: Redsky

Interesting stuff, but how does that explain the rise in free test/lbm that people get when using such a combo?

Your argument is not exclusive, rather it reinforces my statement.
Lignans (from nettle, urtica dioica,and others) increases shbg, this way, more androgens by shbg enters the cell (like you say,more lean body mass).
Designer Supplements, utilises the natural lignan, Divanil™, found in stinging nettle root.

Lignans are members of phytoestrogens.There are three main classes of phytoestrogens: isoflavones,
coumestans, and lignans.

CLINICAL REVIEW.
Phytoestrogens.
ALICE L. MURKIES, GISELA WILCOX, AND SUSAN R. DAVIS
http://jcem.endojournals.org/cgi/reprint/83/2/297.pdf

---------------------------------------

Lignans and Isoflavones have been shown to increase the synthesis and secretion of SHBG by human HepG2 hepatoblastoma cells:

J Steroid Biochem. 1987;27(4-6):1135-44.

Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG).

Adlercreutz H, Hockerstedt K, Bannwart C, Bloigu S, Hamalainen E, Fotsis T, Ollus A.

as for flavones:

Steroids Volume 60, Issue 9 ,September 1995, Pages 656-661
XVII Meeting of the International Study Group for Steroid Hormones

Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures

Mikko Loukovaara, Marion Carson, Aarno Palotie and Herman Adlercreutz

Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, Helsinki, Finland.

and eclypse said: "But too much of it,I think is where the trouble begins".
but how much is to much? because if there is more test, you need more shbg.

Posted by: oswaldosalcedo

Your argument is not exclusive, rather it reinforces my statement.
Lignans (from nettle, urtica dioica,and others) increases shbg, this way, more androgens by shbg enters the cell (like you say,more lean body mass).
Lignans and Isoflavones have been shown to increase the synthesis and secretion of SHBG by human HepG2 hepatoblastoma cells:

J Steroid Biochem. 1987;27(4-6):1135-44.

Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG).

Adlercreutz H, Hockerstedt K, Bannwart C, Bloigu S, Hamalainen E, Fotsis T, Ollus A.

as for flavones:

Steroids Volume 60, Issue 9 ,September 1995, Pages 656-661
XVII Meeting of the International Study Group for Steroid Hormones

Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures

Mikko Loukovaara, Marion Carson, Aarno Palotie and Herman Adlercreutz

Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, Helsinki, Finland.

and eclypse said: "But too much of it,I think is where the trouble begins".
but how much is to much? because if there is more test, you need more shbg.
androgens increases shbg too.

I really know nothing about the physiology of this process. All I know is that for years it has been understood that testosterone is not biologically active until or unless it is freed from shbg. When one takes stinging nettle, the shbg binds to that instead of testosterone. Someone who gets their bloodwork done after using stinging nettle for a period of a few weeks will have a much higher free testosterone score on their blood test, and they will have an increase in sex drive and strength. I don't have any solid answers as to what this all means but I know that I'd like to know what it all means.

Posted by: oswaldosalcedo

Your argument is not exclusive, rather it reinforces my statement.
Lignans (from nettle, urtica dioica,and others) increases shbg, this way, more androgens by shbg enters the cell (like you say,more lean body mass).
Lignans and Isoflavones have been shown to increase the synthesis and secretion of SHBG by human HepG2 hepatoblastoma cells:

J Steroid Biochem. 1987;27(4-6):1135-44.

Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG).

Adlercreutz H, Hockerstedt K, Bannwart C, Bloigu S, Hamalainen E, Fotsis T, Ollus A.

as for flavones:

Steroids Volume 60, Issue 9 ,September 1995, Pages 656-661
XVII Meeting of the International Study Group for Steroid Hormones

Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures

Mikko Loukovaara, Marion Carson, Aarno Palotie and Herman Adlercreutz

Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, Helsinki, Finland.

and eclypse said: "But too much of it,I think is where the trouble begins".
but how much is to much? because if there is more test, you need more shbg.
androgens increases shbg too.

Exept that divanil isn't a phytoestrogen. Also lignan is very broad term and cannot be associated in this context. It can be speculated that divanil's has the ability to increase SHBG expression by forcing the test release from SHBG increases.

About the LBM part, SHBG binds not only testosterone but also other hormones. In fact SHBG levels are more related to circulating E than T

I have tried NP's bulk nettle extract. it is the same as activaTe IME. The stuff is a pain to cap, and I'd rather spend the extra $10 to have DS do the capping for me.

Posted by: whizzo

I have tried NP's bulk nettle extract. it is the same as activaTe IME. The stuff is a pain to cap, and I'd rather spend the extra $10 to have DS do the capping for me.

Is it so awful tasting that you couldn't just drop it in your mouth?

Posted by: eclypz

I really know nothing about the physiology of this process. All I know is that for years it has been understood that testosterone is not biologically active until or unless it is freed from shbg. When one takes stinging nettle, the shbg binds to that instead of testosterone. Someone who gets their bloodwork done after using stinging nettle for a period of a few weeks will have a much higher free testosterone score on their blood test, and they will have an increase in sex drive and strength. I don't have any solid answers as to what this all means but I know that I'd like to know what it all means.

sure bro,maybe there is more free test,proportionally,but there is more shbg too.

your interest to understand is constructive, and these ideas are relatively new, revolutionary.

the skepticism it reminds me the zeigeist concept*, but it happens this way with the new ideas,
well returning to topic,

From: “Few things in life are "free": cellular uptake of steroid hormones by an active transport mechanism.”

“Conventional dogma holds that steroid hormones traverse cell membranes passively, owing to their lipophilic nature. The recently characterized protein megalin, however, functions as a transport protein on cell surfaces to carry steroids across the plasma membrane”

“Recent findings refute the long-held notion that lipophilic hormones, such as androgens and estrogens, solely diffuse into cells by a free, non-specific mechanism”

“recently presented convincing evidence that androgens and estrogens in complex with their carrier protein, the sex hormone binding globulin (SHBG), are endocytosed in cultured cells expressing megalin. The presence of accessible megalin appears to be necessary for optimal internalization of these steroid-SHBG complexes, as evidenced by the reduced levels of uptake observed when receptor-associated protein (RAP, an antagonist of ligand binding to megalin) or megalin-specific antiserum was added, or in cells that lack megalin expression. Furthermore, transcriptional activation (the hallmark of intracellular steroid action) of an androgen-sensitive reporter was observed when androgen-SHBG complexes were added to megalin-expressing cells in vitro; this activity was also inhibited by the addition of RAP”

---------------------------------------------

This way if you arrest all the sbgh (imposible to do because proviron –mesterolone- and winstrol –stanozolol- called shbg inhibitors, binders, competitors etc, are androgens.) you are negating androgens to the cell. the same thing for the nettle (lignans), maybe they bind to shbg but remember there is more sbhg thanks to it (lignans), and I don't deny that it could bind to the shbg.

Take for example this recent post at mindandmuscle.net:

http://www.mindandmuscle.net/forum/index.php?showtopic=26085
coreyx Nov 5 2006, 10:06 AM

Posted by: coreyx

I have low serum testosterone and also low SHGB which results in pretty high and sometimes even above the normal range free testosterone levels. According to the hypothesis that free T is the important factor I should be pretty muscular and also gain a lot of muscles, right? But I don't. I'm not muscular and also don't have much strength which leads me to believe that free T isn't as important as everybody says it is. Free T also has a much shorter half-life than serum testosterone. What I'd really like to know is what happens to the bodybuilders which juice. What happens to the testosterone? I bet that most of the testosterone doesn't stay free but instead it is bound. According to the free T hypothesis the bound testosterone is more or less useless which means that the serum testosterone doesn't play any role and the only thing which matters is free T and I simply don't believe this. I think that having low SHGB sucks, it's not an advantage. I have talked with somebody else on another forum who has the same problems as me. Low serum testosterone, low SHGB and high free T. He got T replacement and didn't feel better at all because his serum testosterone wasn't elevated instead his free T went even higher but it didn't make him feel any better.
I really think that free T is totally overrated, What do you think? Could I be right? I mean if free T was such an important factor then shouldn't I be pretty muscular and strong by nature? But I'm not. The only thing which I notice is that I'm pretty hairy which sucks.

pedagogic, not?

*It is a term that refers to the ethos of a cohort of people, that spans one or more subsequent generations, who despite their diverse age and socio-economic background experience a certain worldview, which is prevalent at a particular period of socio-cultural progression. Zeitgeist is the experience of a dominant cultural climate.