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13/05/2019 5:08 pm
Yeah, Black B I instantly thought that too but I think he is ref to glandular tissue not the adipose. However, the two are so intimately linked in vivo that I would consider them one organ.
13/05/2019 5:58 pm
Of course use of double hydroxylated substances in an oral fashion would lead to quick glucuronidation and secretion, poor uptake in the cells, and the eventual bloodborne concentration, let alone in estrogenic target tissues would be relatively low, even with consumption of 1 gram.If an effect was obtained it would imply intrinsic anabolic activity, as it seems most tissues cannot convert the 3beta back to 3-oxo. Perhaps the liver can though, which could explain possible effect of oral consumption. intrinsic activity, as well as DHT mediated anabolic activity seem less likely. To refer to the ojasoo and raynaud study again, they have low affinity for the AR, and the DHT would be reduced to 3-alpha in muscle.
I agree with most of what you are saying. I first pointed out increased conjugation and excretion long ago, when the diols started being sold as replacements for the diones. Having open hydroxyl groups definitely will speed metabolism and excretion. However, the 3-alpha and 3-beta isomers of androstanediol in proper doses clearly produce a systemic effect. I think when you are shotgunning the liver with a gram of oral per day, enough will make it past to notice, even if the majority of what you consume never will.
Having 17beta hydroxylgroups, I am inclined to think it was more an effect of weak intrinsic activity then hepatic/peripheral conversion to DHT with both androstanediols, but who knows. Neither of the androstanediols were particularly potent as anabolics, but did present some benefit to the user nonetheless. Some could possibly be accounted for by reduced estrogen, but I am quite sure a lot was mediated by androgenic/anabolic activity as well. My only point of contention is the estrognicity; I still do not see any way these diols could be estrogenic, having had too much personal experience with them, and having seen simply zero estrogenicity in all cases.
In this case I am going to have to just disagree with the data, sort of like how I cannot accept exemestane is safe for steroid users' HDL levels, even though certain studies on postmenopausal women show them to be.
13/05/2019 6:46 pm
Yeah, Black B I instantly thought that too but I think he is ref to glandular tissue not the adipose. However, the two are so intimately linked in vivo that I would consider them one organ .
Exactly.
Many studies have demonstrated the importance of the interactions between the glandular tissue and the fatty tissue surrounding the mammary gland. Up and downregulation of aromatase activity and estrogenic receptors.
CASE 2 : the binding of Androgen receptor to estrogen response elements induced by certain ligands. I won't go into detail on this too much as I know I adressed this before.For nandrolone it has been demonstrated that it can bind the AR and cause the AR to activate estrogen-responsive genes. Nandrolone is 60% as estrogenic as estradiol
Please can you quote references about.
Topic starter 13/05/2019 7:44 pm
Exactly.
Many studies have demonstrated the importance of the interactions between the glandular tissue and the fatty tissue surrounding the mammary gland. Up and downregulation of aromatase activity and estrogenic receptors.
Its a chicken and egg discussion, as prior to the breast there is no adipose deposition in the area. So where is the aromatase coming from that initiates gyno ? Not adipose tissue as it isn't present in any significant amount prior to the development of mammary tissue, so your arguments holds no ground.
quote:
Please can you quote references about.
Of course, like I said in the initial post, I discussed this before, a simple search would have yielded :
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.
13/05/2019 8:39 pm
Its a chicken and egg discussion, as prior to the breast there is no adipose deposition in the area. So where is the aromatase coming from that initiates gyno ? Not adipose tissue as it isn't present in any significant amount prior to the development of mammary tissue, so your arguments holds no ground.
The mammary gland is naturaly surrounding by adipose tissues. We know that estrogens induce proliferation of their receptors. If the adipose tissue has abnormal or bad regulate aromatase activity, local excessive androgens conversion to estrogens will occur and upregulation of the ER. Do not need excessive adipose tissue to have gyno and local abnormal aromatase activity.
The role of androgens and the AR has to be clarify but could be important in the control of the gland size.
quote:
Of course, like I said in the initial post, I discussed this before, a simple search would have yielded
Sorry I have seen it too late, in fact after I have posted.
Topic starter 13/05/2019 9:20 pm
[B]The mammary gland is naturaly surrounding by adipose tissues. We know that estrogens induce proliferation of their receptors. If the adipose tissue has abnormal or bad regulate aromatase activity, local excessive androgens conversion to estrogens will occur and upregulation of the ER. Do not need excessive adipose tissue to have gyno and local abnormal aromatase activity.
The role of androgens and the AR has to be clarify but could be important in the control of the gland size.
I think you misunderstand me. In a normal male, there is no mammary gland to speak of, and hence no adipose deposition surrounding it, meaning there is no local source of aromatase prior to the development of gyno. Hence, the cause of gyno in a normal male can never be LOCAL aromatisation, but has to be systemic.
quote:
Sorry I have seen it too late, in fact after I have posted.
No sweat. I'm probably releasing one or two chapters of the book as promotion in the near future and the nandrolone profile will likely be included, which discusses it in much greater detail.
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.
14/05/2019 8:48 am
spoke with a thoracic surgeon who said that there is glandular tissue and adipose in the male areolar area in men without clinical gyno is there but not as developed as in women. What post did I not see Big Cat that Black B saw too late??
I am not taking sides nor do i want to try to make a small point and distract from a bigger picture.
My apologies in advance
14/05/2019 9:34 am
[B]I think you misunderstand me. In a normal male, there is no mammary gland to speak of, and hence no adipose deposition surrounding it, meaning there is no local source of aromatase prior to the development of gyno. Hence, the cause of gyno in a normal male can never be LOCAL aromatisation, but has to be systemic.
I must disagree. And there are some evidences that gyno could be a local disturbance.
You can developp gyno with normal T and estrogens levels.
quote:
Originally posted by jawbone spoke with a thoracic surgeon who said that there is glandular tissue and adipose in the male areolar area in men without clinical gyno is there but not as developed as in women.
Exactly what I want to say.
14/05/2019 10:32 am
Aromatization can take place in male adipose tissue in general. How much is usually in porportion to BF levels. This means BC is wrong LOL. uh-oh
Seabiscuit Hogg is a fictious internet character. It is not recommended that you receive medical advice from fictious internet characters.
SBH :)
Topic starter 14/05/2019 11:08 am
[B]I must disagree. And there are some evidences that gyno could be a local disturbance.
You can developp gyno with normal T and estrogens levels.
How is that evidence for local aromatisation ? Any disturbance can be the result of systemic aromatisation. Where do you propose the local aromatisation takes place if no adipose tissue is present ?
quote:
Exactly what I want to say.
There is some glandular tissue (or we would have no nipples), but no adipose deposition to speak of.
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.
Topic starter 14/05/2019 11:41 am
Aromatization can take place in male adipose tissue in general. How much is usually in porportion to BF levels. This means BC is wrong LOL. uh-oh
Uhm, were you paying attention to this discussion ?
I never said anything like that, on the contrary, I even stated the very fact. That aromatisation occurs in peripheral tissues and liver, and then systemically distributes itself, to among other places the mammary tissue (which expresses no aromatase). What BB and the others seem to want to propose is that the aromatisation is local from adipose tissue near the mammary gland. However in males the mammary gland is barely developed and there is no adipose tissue deposition to speak of in the area, ruling out any significant degree of local aromatisation.
As opposed to 3beta-androstanediol formation, which is formed directly in mammary tissue, as well as most other tissues.
Or to reiterate from the original post :
quote:
This is true, but estrogens are produced by aromatase and dumped into circulation and have to make their way to mammary tissue. Mammary tissue itself contains no aromatase. 3beta-androstanediol is produced by AKR1C, and this gene is expressed directly in mammary tissue, leading to direct local conversion if DHT is present in the tissue. 5AR is also present in mammary tissue. This means despite weaker activity, the presence of the product in the tissue is likely higher.
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.
14/05/2019 12:24 pm
jb
14/05/2019 1:07 pm
How is that evidence for local aromatisation ? Any disturbance can be the result of systemic aromatisation. Where do you propose the local aromatisation takes place if no adipose tissue is present ?
There is some glandular tissue (or we would have no nipples), but no adipose deposition to speak of.
Normal healthy men have both glandular tissue and adipose tissue surroundig it.
There is a lot of different cases of gynecomastia and lot of diseases or drugs can lead to breast enlargement in men. For our discussion, I think to examine idiopathic gyno in normal healthy men is the most relevant.
In many idiopathic gynos, the biological parameters (T, estrogens included) are in the normal range.
Estrogens that stimulate breath growth are converted locally in the fatty tissue surrounding the glands from androgen precursors.
Evidences for a local origin of some gynecomastia in healthy men (quoted from Braunstein article) :
Braunstein :"An imbalance between estrogen action relative to androgen action at the breast tissue level results in gynecomastia."
"Finally, in some individuals, gynecomastia may result from an enhanced sensitivity of breast tissue to normal concentrations of free estrogens and androgens."
"Aromatase activity has been demonstrated in the placenta, ovary, testes, brain, skin fibroblasts, adipocytes, normal breast stromal cells ..."
"... raising the possibility that local dys-regulation of breast tissue aromatase may lead to a local estrogen to androgen imbalance."
Quoted from : Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia.
"The pathogenesis of idiopathic gynecomastia, which shows no imbalance in serum estrogens and androgens levels unlike gynecomastia of other causes, is unknown. It seems to be of interest to study the in situ aromatase expression in idiopathic gynecomastia to investigate a possible involvement of intratumoral biosynthesis of estrogens in the pathogenesis of this disease."
"... a high estrogen milieu induced by increased aromatase expression is speculated to play some role in the pathogenesis of idiopathic gynecomastia."
Quoted from : Gynecomastia--pathogenesis, diagnosis and treatment.
"Gynecomastia is a benign, unilateral or bilateral enlargement of the male breast due to the imbalance between the androgens and estrogens at the breast tissue level."
Quoted from : Biology of aromatase in the mammary gland.
"Principally, the estrogen synthesized within these compartments is probably only biologically active at a local tissue level in a paracrine or 'intracrine' fashion. Thus the total amount of estrogen synthesized by these extragonadal sites may be small, but the local tissue concentrations achieved are probably quite high, and exert significant biological influence locally."
Even in normal cell and in healthy subject we can have an aromatase dysregulation :
"Increased aromatase activity in which normal amounts of precursors are produced but are converted into estrogens at an enhanced rate can be due to increased activity in normal tissues, dysregulation of P450arom ..."
Increased aromatase expression in the stromal cells could contribute to the increment in the in situ estrogen concentration and the development of gynecomastia.
Evidences for a plurifactorial disease :
Quoted from : Presence of luteinizing hormone/human chorionic gonadotropin receptors in male breast tissues.
"Receptors for LH/human chorionic gonadotropin (HCG) have been found in a variety of nongonadal tissues including the female breast. Using in situ hybridization and immunohistochemistry, we demonstrated the presence of LH/hCG receptor mRNA and protein in normal male breast tissue obtained at autopsy (n = 4) and archival samples of benign gynecomastia (n = 14) and male breast carcinoma (n = 5). Although the function of these receptors remains to be determined, the findings suggest the possibility that LH and hCG may play a role in the pathogenesis of male breast disorders."
Influence of leptin, quoted from : Leptin levels in boys with pubertal gynecomastia.
CONCLUSION: The presence of higher leptin levels in boys with pubertal gynecomastia indicates that leptin may be involved in the pathogenesis of pubertal gynecomastia. The role of circulating leptin in pubertal gynecomastia is probably related to increase in estrogen and/or estrogen/ androgen ratio by the stimulating effect of leptin on aromatase enzyme activity in both adipose and breast tissues, or a direct growth stimulating effect of leptin on mammary epithelial cells, or increase in sensitivity of breast epithelial cells to estrogen with inducing functional activation of estrogen receptors by leptin in breast tissue.
Receptors involved in gynecomastia ? Quoted from : Steroid hormone receptors in male breast diseases.
"With gynecomastic tissue, the proportion of receptor-positive patients was 20% ER, 20% PR, 20% AR, and 45% GR."
In a lot of studies good results are obtained with SERM and/or AI, demonstrating the importance (but certainly not the sole) of aromatase and estrogens.
Topic starter 14/05/2019 1:56 pm
Do you have the complete studies, because I see no proof for adequate local conversion presented along with the quotes you provide, surely these researchers must quote some source when they say this ?
On your last note : The fact that SERMS and AI's heko in gyno in no way points to a local effect in breast tissues, both are used orally and therefore systemically. I don't think anyone questions the role of estrogens in gyno, so again, this is a moot point. The topic of this thread relates to the appearance of gyno in the absence of estrogens. The issue you seem to be having with the argument is my statement that AKRC1 is expressed much higher at the local level, than aromatase.
On a final note, gynocomastia in those men was initiated by an upregulation of aromatase or the ER, in the presence of normal levels of estrogen. If you refer to the opening post, then you will see that I was providing an explanation for rare cases of gyno with non estrogenic drugs, ie cases where estrogen levels are severely depressed, (in men WITHOUT idiopathic gyno) and gyno still develops.
So perhaps it would help if you clarify what you are arguing against ? Is it just the statement that I made that AKR1C is expressed at a higher level in breast tissue and therefore opens the possibility that 3b-androstanediol may act as an estrogen in the absence of aromatisation since 5a-reduction is increased, as I initially thought and which is worthwhile discussion, or is your argument something different entirely ?
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.
14/05/2019 2:30 pm
I apologize, my english is sometimes too poor to explain my whole idea.
I read and take interest for gynecomastia in normal healthy men for long time.
What I want to say :
- no proof that gynecomastia could occur without T/E2 ratio disturbance, aromatase dys-regulation, 5-a reductase deficiency etc or other endocrine parameters that involved an estrogenic effect mediated by estrogens and their own receptors.
- the rare cases of gyno with non estrogenic drugs you referred are not documented. And it does not mean that the traditional reasons advanced in breast enlargment in normal healthy men are not valid.
- no proof that non-aromatisable steroids or nandrolone are able to promote gyno by an estrogenic AR-mediated effect.
- the local origin is often advanced in studies because the absence of disturbance in the biological parameters and the absence of other female signs.