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09/12/2018 8:06 am
[B]tamoxifen can be used by a woman with a breast cancer history, its even the treatment of choice, you cannot say the same thing with nandrolone in a man with prostate cancer.
But it could be, if dosed correctly, and that, after all, is the point.
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Yes, but remember that the introduction of a third double bond (4,9,11 trienes) displaces the compound toward AR.
Actually, in the graph, you will note that as a group 4,9,11-trienes are still more prone to PR binding than AR binding ...
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Trenbolone is a potent PR agonist, but its a very potent AR agonist too.
Yes, and for the second time you managed to ignore that the passage was about 19Nor-4,9-androstadiene-3-one,17b-ol, and not trenbolone.
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You can turn it over and over but actually, AAS are steroids derivatived from the natural androgen T with androgenic and anabolic properties and in some extent because the opposite action of the androgenic to estrogenic activity in many (but not all) tissues : they are anti-estrogenic too. That what I say that they are anti-e "by nature".
But they aren't, that was the whole point of this debate. It is perfectly possibly for AAS to cause more estrogenic effects than Testosterone for the same level of anabolism. Making them mg for mg more estrogenic and thus anything BUT anti-estrogenic by nature.
And like you said, you can turn that over and over, but that won't change the facts. AAS are Anabolic, androgenic, and steroids. Not only is it possibly for classical AAS to be sufficiently more estrogenic, some estrogens themselves fall under this denominator. Your entire contention during this debate was something about the prime receptor being activated, and several examples have already pointed out that this is a rarely used and highly arbitrary criterium, as many progestins are ranked as "anti-progestins" or AAS, and vice versa.
The point is, AAS are not by definition, by nature or even the grace of your imagination "anti-estrogenic"
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
09/12/2018 8:49 am
Let's return to the strict definition, they are steroids and anabolic and androgenic. By itself, androgenicity is the opposite of estrogenicity, in some tissues, androgenic action repress the estrogenic action. So androgenic properties mean as well, in some extent, anti-estrogenic properties (except in tissues where androgens and estrogens work together).
09/12/2018 9:40 am
Let's return to the strict definition, they are steroids and anabolic and androgenic. By itself, androgenicity is the opposite of estrogenicity, in some tissues, androgenic action repress the estrogenic action. So androgenic properties mean as well, in some extent, anti-estrogenic properties (except in tissues where androgens and estrogens work together).
That's like saying A and B are the same, except where they are different ...
There is no direct opposition to either action by the other. They influence each other, sure, but then what two systems in the human body don't ? androgens don't block the ER, AR's are more likely to heterodimerize with ANY other nuclear receptor than the ER, and between these two, of all 5 classical nuclear receptors, there is the least amount of competition for co-factors.
If this is your argument, then i can use the very same argument to state the opposite :
"In some tissues androgens and estrogens work together, so by nature, androgens are pro-estrogenic ... (except in tissues where they oppose each other)"
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
09/12/2018 10:16 am
Big Cat,many androgen's package inserts (testosterone,halotestin and if i remember well proviron) state that they are used in the last stages of female breast cancer.
If not for their "antiestrogenic properties" or their androgen to estrogen ratio altering properties (which can have antiestrogernic results) then what for ? For what alse would women in the last stage of breast cancer need androgens ?
09/12/2018 10:56 am
androgens in the last stage of hormone sensitive breast cancer have been shown to mediate via the ar in the breast tissue and have NO relationship to the er. The most common androgen used for this is masteron although nandrolone and even testosterone have been used.
jb
09/12/2018 11:46 am
Big Cat,many androgen's package inserts (testosterone,halotestin and if i remember well Proviron) state that they are used in the last stages of female breast cancer.
If not for their "antiestrogenic properties" or their androgen to estrogen ratio altering properties (which can have antiestrogernic results) then what for ? For what alse would women in the last stage of breast cancer need androgens ?
Yes, I'm going to build on what jb said to further answer this. All androgens have been shown to mediate positive effects on breast cancer. However a cancer is not a normal condition. The effect of androgens on breast cancer has nothing to do with estrogens.
For example, chemotherapy helps for breast cancer, i'm sure you are not going to tell me chemotherapy is anti-estrogenic .
In fact this very thing further proves my point. The reason masteron is clinically used for this, despite better results with testosterone and nandrolone, is that masteron is non-estrogenic, where testosterone and nandrolone are estrogenic.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
09/12/2018 12:20 pm
"In some tissues androgens and estrogens work together, so by nature, androgens are pro-estrogenic ... (except in tissues where they oppose each other)"
And I think we speak about the breast tissues (?) where androgens and estrogens have an opposite action. So, because they are, by definition, androgenic AAS are anti-estrogenic at the breast tissue (I assume it is the subject here).
09/12/2018 1:13 pm
The effect of androgens on breast cancer has nothing to do with estrogens.
Androgens are used in hormonodependant advanced breast cancers. It has to do with estrogens, like the other medecines used like SERM or AI.
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For example, chemotherapy helps for breast cancer, i'm sure you are not going to tell me chemotherapy is anti-estrogenic .
Chemotherapy is a treatment of cancer, it is not specific to the breast cancer.
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In fact this very thing further proves my point. The reason masteron is clinically used for this, despite better results with testosterone and nandrolone, is that masteron is non-estrogenic, where testosterone and nandrolone are estrogenic.
T and N are estrogenic ... really (?) ... give T and N to a girl and then come back and say if they are androgenic or estrogenic compounds. They are in fact more potent androgens than drostanolone.
Boys with androgenic deficiencies experiment estrogenic effects.
09/12/2018 2:12 pm
And I think we speak about the breast tissues (?) where androgens and estrogens have an opposite action. So, because they are, by definition, androgenic AAS are anti-estrogenic at the breast tissue (I assume it is the subject here).
First of all your statement was that androgens are anti-estrogenic, I don't see how that would solely pertain to breast tissue.
Secondly, how do you construe the actions of androgens in reducing tumors to be anti-estrogenic, because these actions are opposite to what estrogen does in that tumor ?
It may also be wise to remind you that one tumour is not the same as another. There are breast tumors where androgens will have no effect. Tumors are malignant tissue, that are dedifferentiated and have little in common with the tissue of origin.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
09/12/2018 2:50 pm
[B]Androgens are used in hormonodependant advanced breast cancers. It has to do with estrogens, like the other medecines used like SERM or AI.
The effects of testosterone and nandrolone were higher than for masteron, despite their estrogenic nature. The effect of the androgen in this case was entirely set apart from the effects of estrogens. The androgens in no way influence the estrogenic cascade, and initiated their benefit independently from estrogen, the estrogen receptor and the estrogen response elements.
Ie, the effects of the androgen on breast cancer have nothing do with estrogens.
By the way, this abstract may interest you :
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Oncol Rep. 2004 Oct;12(4):709-16. Related Articles, Links
Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland.
Zhang J, Sun Y, Liu Y, Sun Y, Liao DJ.
Transgenic and Knockout Animal Laboratory, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
Many studies have suggested that elevated estrogens and androgens may be etiologically related to the development of breast cancer, endometrial cancer and uterine leiomyomas. We and other investigators have previously shown that estrogen and androgen are synergistic in the induction of mammary carcinogenesis in the Noble rat. However, the mechanisms behind the synergy is unknown, and it is unclear whether such synergy is unique for the Noble rat and for the mammary gland. In this study we treated female FVB mice with 17beta-estradiol (E2) and 5alpha-dihydrotestosterone-bezonate (DHT-B), alone and in combination, using silastic tubing for 2-7 months. The results showed that DHT-B alone induced proliferation of uterine endometrial epithelium and myometrial smooth muscle cells, whereas E2 alone induced much more pronounced growth of endometrial epithelium without affecting smooth muscle cells. Combined treatment with E2+DHT-B caused an even more severe hyperplasia of endometrial epithelium and myometrial muscle cells, compared with the treatment with each hormone alone. Uterine leiomyomas were observed in 2 of 6 mice at 7 months of combined treatment but not in any of 6 or 7 mice receiving each single hormone. DHT-B alone induced growth and secretion of mammary ductal cells, as well as growth of mammary stroma. E2 alone stimulated much more pronounced growth of both ductal cells and alveolar cells and secretion of alveolar cells, but had no effect on mammary stroma. Treatment with both E2 and DHT-B caused more severe hyperplasia of mammary ducts and alveoli, compared to the treatment with each hormone alone. Intraductal hyperplasia occurred early and frequently in the E2+DHT-B- treated mice, but no mammary tumors were observed. These results suggest that E2 and DHT-B have synergistic effects on the growth of uterine endometrial epithelium and myometrial muscle cells, as well as mammary epithelial ducts and alveoli.
breast, endometrium and uterus ... those are estrogen-dependent organs aren't they ? Typically female ? So I guess by your reasoning, if androgens increase the risk of cancer in these area's, they must be pro-estrogenic right ?
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Chemotherapy is a treatment of cancer, it is not specific to the breast cancer.
Your statement was that because androgens opposed the action of estrogens , they were anti-estrogenic.
Androgens are also not specific to breast cancer. as the abstract above shows, androgens are most likely to promote than help breast cancer. Just because androgens in the past have been able to alleviate one type of mammary carcinoma does not make them a universal treatment for ALL mammary carcinoma's. I understand this is hard for people without a background in genetics (which I confess I don't know if you have) but one breast cancer is not the same as the next.
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T and N are estrogenic ... really (?) ... give T and N to a girl and then come back and say if they are androgenic or estrogenic compounds. They are in fact more potent androgens than drostanolone.
No question. T and N are more potent androgens than drostanolone.
T and N are also more potent estrogens than drostanolone, hence the reason drostanolone was used to treat certain mammary tumours, and not T and N
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
09/12/2018 3:28 pm
The effects of testosterone and nandrolone were higher than for masteron, despite their estrogenic nature.
Because they are far more androgenic than estrogenic.
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The effect of the androgen in this case was entirely set apart from the effects of estrogens.
No, androgens work in hormono-dependant breast cancer because their effects are linked to their anti-estrogenic nature.
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The androgens in no way influence the estrogenic cascade, and initiated their benefit independently from estrogen, the estrogen receptor and the estrogen response elements.
Indenpendently in term of receptor target, but in some tissues they opposite the action of estrogens.
"Females treated with androgens exhibited similar involutionary changes as those seen in breast of menopausal women such as marked reduction of glandular tissue , involution of the lobuloalveolar structures and prominence of fibrous connective tissue, but presence of only small amounts of fat tissue." (1)
A marked reduction of glandular tissue is not an anti-estrogenic effect ?
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breast, endometrium and uterus ... those are estrogen-dependent organs aren't they ? Typically female ?
"The antiestrogenic effect of MENT was also blocked by flutamide.
These results suggest that the uterotropic and antiestrogenic effects of androgens are mediated via AR. It is concluded that the increase in uterine weight caused by MENT is attributable to its anabolic effects." (2)
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Your statement was that because androgens opposed the action of estrogens , they were anti-estrogenic.
To opposite and repress estrogenic action is an anti-estrogenic effect.
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Androgens are also not specific to breast cancer. as the abstract above shows, androgens are most likely to promote than help breast cancer. Just because androgens in the past have been able to alleviate one type of mammary carcinoma does not make them a universal treatment for ALL mammary carcinoma's.
Of course they are not an universal treatment for all mammary cancers, all breast cancer are not hormono-dependant, even SERM and AI are not but they are anti-estrogenic drugs, aren't they ?
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I understand this is hard for people without a background in genetics (which I confess I don't know if you have) but one breast cancer is not the same as the next.
Genetic is not my main school subject but like all scientific student I learn it.
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T and N are also more potent estrogens than drostanolone, hence the reason drostanolone was used to treat certain mammary tumours, and not T and N
With less effectiveness ...
Even if T and N have also estrogenic properties, they are far more androgenic than estrogenic, despite what you claim.
09/12/2018 4:04 pm
[B]Because they are far more androgenic than estrogenic.
Yes, but they are estrogenic. And if a compound is estrogenic, it cannot, by definition, be anti-estrogenic in the same context. You just contradicted yourself
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No, androgens work in hormono-dependant breast cancer because their effects are linked to their anti-estrogenic nature.
We've been over this, other things like chemo work in hormone-dependant breast cancers as well and are not anti-estrogenic. The fact that the cancer is hormone-dependant indicates that it responds to estrogenic deprivation. That is an extremely far-fetched notion to then suggest that just because something helps it is therefor necessarily anti-estrogenic. One is not related to the other.
The androgens, in the breast, show cross intereference with the actions of the estrogen, thereby mediating a reduction in the cancer-promoting effect of the estrogens, without influencing estrogen, ER, the ER cascade or the estrogen response elements.
If every substance that had an opposite result in one or more tissues, despite reinforcing actions in other tissues, was named anti-something, you'd get some really ridiculous things.
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Indenpendently in term of receptor target, but in some tissues they opposite the action of estrogens.
They have some opposing actions in some tissues. That does not constitute an anti-estrogenic action, as it does not mean they oppose ALL actions (which would be the definition of anti-estrogenic), nor in this case do they even oppose ANY action in some tissues. Since they also do not show a direct influence on the actions of the estrogen itself (the opposing action is mediated by a different cascade on the same tissue causing the opposing action) they are not anti-anything really in that context.
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A marked reduction of glandular tissue is not an anti-estrogenic effect ?
No it is not. The same effect can be caused by a multitude of apoptotic factors, chemo, and xenobiotics influencing any part of downstream cascade, non of which are considered anti-estrogens.
If the reduction in glandular tissue was caused by estrogen deprivation or any intervention downstream of the estrogen receptor leading to the same effect THEN it would be anti-estrogenic.
In this case you haven't the slightest idea which cascade was influenced to cause a reduction in tissue, but you do know it wasn't the estrogen cascade. In same line, simply reducing prostate tissue size is not necessarily an anti-androgenic effect.
[quite]To opposite and repress estrogenic action is an anti-estrogenic effect.
But it only conditionally (not ubiquitously) opposes estrogenic action and IT DOES NOT REPRESS estrogenic action. Hence it is not an anti-estrogen by either of those two definitions.
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Of course they are not an universal treatment for all mammary cancers, all breast cancer are not hormono-dependant, even SERM and AI are not but they are anti-estrogenic drugs, aren't they ?
They aren't even treatment for all hormonedependant cancers, since SERMS do often still appear tobe beneficial in cancers where androgens are not ...
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Genetic is not my main school subject but like all scientific student I learn it.
Breast cancer can be caused by a multitude of insertions, deletions and mutations in a multitude of genes ranging from proto-oncogenes and tumor repressors to DNA repair genes. These can be either dominant spontaneous tumours or recessive genetic tumours. This means that breast cancer can take on several thousand different forms, with different response to treatment, different level of progression and agression.
In all cases tumours share a number of similar trait : they are dediffereniated cells that have lost control of their proliferation. The effects in cancers therefor are in no way representative for normal tissue responses to the same products.
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With less effectiveness ...
Even if T and N have also estrogenic properties, they are far more androgenic than estrogenic, despite what you claim.
I never claimed anything different. In fact I claimed just what you said. They are more androgenic than estrogenic, but they have estrogenic properties and are therefore by definition NOT anti-estrogenic.
That was your statement ....
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
09/12/2018 4:52 pm
Yes, but they are estrogenic. And if a compound is estrogenic, it cannot, by definition, be anti-estrogenic in the same context. You just contradicted yourself
I totally disagree, a compound can be both estrogenic AND anti-estrogenic, depending which action or tissue you refer to.
I quote scientists from the Center for Biomedical Research of New York: "Synthetic androgens exhibit estrogenic and antiestrogenic and progestational activities in addition to their androgenic effects."
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We've been over this, other things like chemo work in hormone-dependant breast cancers as well and are not anti-estrogenic. The fact that the cancer is hormone-dependant indicates that it responds to estrogenic deprivation. That is an extremely far-fetched notion to then suggest that just because something helps it is therefor necessarily anti-estrogenic. One is not related to the other.
So maybe your article about the synergistic effects of androgen and estrogen on the mouse uterus and mammary gland is not relevant too ...
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The androgens, in the breast, show cross intereference with the actions of the estrogen, thereby mediating a reduction in the cancer-promoting effect of the estrogens, without influencing estrogen, ER, the ER cascade or the estrogen response elements.
Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression.
Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
"These observations showing androgen-induced down-regulation of mammary epithelial proliferation and ER expression suggest that combined estrogen/androgen hormone replacement therapy might reduce the risk of breast cancer associated with estrogen replacement. In addition, these novel findings on tamoxifen's androgen-like effects on primate mammary epithelial sex steroid receptor expression suggest that tamoxifen's protective action on mammary gland may involve androgenic effects."
"An antiestrogenic action of androgens in human breast cancer cells.
MacIndoe JH, Etre LA.
We have recently observed that androgens prevent the estrogen-dependent augmentation of cytoplasmic progesterone receptor (PRc) in MCF-7 human breast cancer cells and now report the results of studies that further characterize this new example of sex steroid antagonism. Using a single saturating dose assay to monitor changes in MCF-7 PRc concentration, we have observed that androgens are capable of inhibiting both the estrogenic induction and the ongoing stimulation of PRc synthesis, but have no apparent effect upon basal concentrations of this receptor. Both testosterone and dihydrotestosterone (DHT) demonstrate similar degrees of antiestrogenic activity at concentrations between 10(-10)--10(-8) M. Furthermore, a 10(-8)-M concentration of either androgen completely inhibits the stimulation of PRc synthesis by 10(-11)--10(-8) M 17 beta-estradiol (E2). This inhibitory effect is maintained during the continued presence of either testosterone or DHT, but rapidly disappears after the withdrawal of androgen from the culture medium. The specific nuclear binding of 17 beta-[3H]estradiol over time appears to be similar in cultures incubated in the presence and absence of 10(-8) M DHT. This observation suggests that androgens do not inhibit estrogen action by interfering with the formation, activation, nuclear binding, or nuclear processing of estrogen-receptor complexes. The estrogenic stimulation of PRc is not diminished by the 5 beta-epimer of DHT, and the inhibitory activity of DHT itself is blocked by several different antiandrogens. These findings provide substantial support for the concept that the antiestrogenic effect of androgens is mediated by an androgen receptor mechanism. These results may provide new insights into the clinically apparent antagonistic effects of estrogens and androgens upon both normal and malignant human breast tissues."
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If every substance that had an opposite result in one or more tissues, despite reinforcing actions in other tissues, was named anti-something, you'd get some really ridiculous things.
Sorry I do not really understand what you want to mean. If something opposite the action of something else the action is said to be "anti" and if it increase the action it is said to be "pro". This is the sense of these words.
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as it does not mean they oppose ALL actions
Who says the contrary ?
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(which would be the definition of anti-estrogenic)
To be an anti-estrogen a compound must be anti-estrogenic in all actions ?
SERM are refered in the scientific litterature as "anti-estrogens" but they have both estrogenic and anti-estrogenic properties.
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If the reduction in glandular tissue was caused by estrogen deprivation or any intervention downstream of the estrogen receptor leading to the same effect THEN it would be anti-estrogenic.
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They aren't even treatment for all hormonedependant cancers, since SERMS do often still appear tobe beneficial in cancers where androgens are not ...
Yes SERM are more effective.
09/12/2018 5:42 pm
I wish I was educated enough to argue with you guys
09/12/2018 6:18 pm
Effects of long-term androgen administration on breast tissue of female-to-male transsexuals.
Long-term administration of androgens in female-to-male transsexuals causes marked reduction of glandular tissue and prominence of fibrous connective tissue. These changes are similar to those observed at the end-stage of menopausal mammary involution.