Nandrolone conversion to estrogen by aromatase or liver? [ADVANCED QUESTION]

[pogue]

I posted this over at Cutting Edge Muscle, but since that forum is kind of dead, I thought I would repost over here and see if I can get an answer. Basically, I'm trying to figure out how nandrolone converts to estrogen, what rate it converts it, does it convert through aromatase and how, and does it also convert through Cytochrome P450 how often and what is the % (if these figures are even available).


I'm doing some research on nandrolone for an article I'm writing and I'm getting conflicting information on how nandrolone interacts with the aromatase enzyme and how it may convert to estrogen in the liver via P450.

There is a study referenced in many articles having to do with this titled: Can 19-nortestosterone derivatives be aromatized in the liver of adult humans?. However, it many references two progesterone based birth control formulas called tibolone and norethisterone.

Climacteric. 2007 Aug;10(4):344-53.
Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?
Kuhl H1, Wiegratz I.
Author information

1Department of Obstetrics & Gynecology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany.
Abstract
CONTEXT:
Previous studies in postmenopausal women have demonstrated that, after oral administration of norethisterone, a small proportion of the compound is rapidly converted into ethinylestradiol. The shape of the concentration - time curve suggested that this occurred in the liver. The results were confirmed by in vitro investigations with adult human liver tissue. In 2002, it was shown that, after oral treatment of women with tibolone, aromatization of the compound occurred, resulting in the formation of a potent estrogen, 7 alpha-methyl-ethinylestradiol. The result has been called into question, because the adult human liver does not express cytochrome P450 aromatase, which is encoded by the CYP 19 gene. Moreover, it has been claimed that the serum level of 7 alpha-methyl-ethinylestradiol measured by gas chromatography/mass spectrometry was an artifact.

REPLY:
Aromatization of steroids is a complex process of consecutive oxidation reactions which are catalyzed by cytochrome P450 enzymes. The conversion of the natural C19 steroids, testosterone and androstenedione, into estradiol-17beta and estrone is dependent on the oxidative elimination of the angular C19-methyl group. This complex key reaction is catalyzed by the cytochrome P450 aromatase, which is expressed in many tissues of the adult human (e.g. ovary, fat tissue), but not in the liver. However, 19-nortestosterone derivatives are characterized by the lack of the C19-methyl group. Therefore, for the aromatization of these synthetic steroids, the action of the cytochrome P450 aromatase is not necessary and the oxidative introduction of double bonds into the A-ring can be catalyzed by other hepatic cytochrome P450 enzymes. The final key process in the formation of a phenolic A-ring, both in natural androgens and 19-nortestosterone derivatives, is the enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety, which occurs without the action of enzymes.

CONCLUSION:
19-nortestosterone derivatives (norethisterone, norethynodrel, tibolone) can readily be aromatized in the adult human liver. This leads to the formation of the potent estrogens ethinylestradiol from norethisterone or norethynodrel and 7 alpha-methyl-ethinylestradiol from tibolone. This may have clinical consequences, e.g. the elevated risk of venous thromboembolic disease in premenopausal women treated with high doses of norethisterone for bleeding disorders, or the elevated risk of stroke or endometrial disease in postmenopausal women treated with tibolone.

Here are some quotes from the full text:

Aromatization of steroids is a complex process of consecutive oxidation reactions which are catalyzed by cytochrome P450 enzymes. The conversion of the natural C19 steroids, testosterone and androstenedione, into estradiol-17B and estrone is dependent on the oxidative elimination of the angular C19-methyl group. This complex key reaction is catalyzed by the cytochrome P450 aromatase, which is expressed in many tissues of the adult human (e.g. ovary, fat tissue), but not in the liver. However, 19-nortestosterone derivatives are characterized by the lack of the C19-methyl group. Therefore, for aromatization of these synthetic steroids, the action of the cytochrome P450 aromatase is not necessary and the oxidative introduction of double bonds into the A-ring can be catalyzed by the other hepatic cytochrome P450 enzymes. The final key process in the formation of a phenolic A-ring, both in natural androgens and 19-nortestosterone derivatives, is the enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety, which occurs without the action of enzymes.

Conclusion 19-nortestosterone derivatives (norethisterone, norethynordrel, tibolone) can readily be aromatized in the adult human liver. This leads to the formation of the potent estrogens ethinylestradiol from norethisterone or norethynodrel and 7a-methyl-ethinylestradiol from tibolone. This may have clinical consequences, e.g. the elevated risk of venous thromboembolic disease in premenopausal women treated with high doses of norethisterone for bleeding disorders, or the elevated risk of stroke or endometrial disease in postmenopausal women treated with tribolone.

AROMATIZATION OF 19-NORTESTOSTERONE DERIVATIVES

The situation is completely different in the aromatization of 19-nortestosterone derivatives like norethynodrel or tibolone. The term ‘19-nor’ represents the lack of an angular C19 methyl group. Therefore, the action of the CYP arom, which eliminates the angular C19 methyl group of natural androgens, is not needed for the aromatization of 19-nortestosterone derivatives (Fig 2).
Tibolone, which is the 7a-methyl-derivative of norethynodrel (Fig3), contains a double bond between C5 and C10 and a keto group at C3.

CONCLUSIONS

The conversion of the natural androgens testosterone and androstenedione into estradiol and estrone, which is dependent on the oxidative elimination of the C19-methyl group, is catalyzed by the classical cytochrome P450 aromatase system. Contrary to this, 19-nortestosterone derivatives can be aromatized by other hepatic cytochrome P450 enzymes after simple oxidative introduction of double bonds. This mechanism allows the rapid conversion of a small proportion of norethisterone into ethynlestradiol and of tibolone into 7a-methyl-ethinylestradiol, which occrs rapidly in the liver after oral administration.

But, my question is, does this unusual route of administration apply to actual 19nortestosterone (nandrolone) or just it's derivatives?

Further, in a book titled Doping in Sports (Handbook of Experimental Pharmacology, Vol. 195) 1st Edition
by Detlef Thieme (Editor), Peter Hemmersbach (Editor)

Another important difference between testosterone and nandrolone biotransformation is related to its ability to be aromatised into an oestrogen. Unlike testosterone, nandrolone is not a substrate for the cytochrome P450 aromatase enzyme catalysed transformation to an oestrogen (Behre et al. 2001), although nandrolone-
related substances may undergo aromatisation via a different pathway in the liver

(Kuhl and Wiegratz 2007).

So, my main question is, by what pathway does nandrolone convert to estrogen? Is it through the normal aromatase pathway that testosterone converts? Or is there another pathway that converts via the liver to estrogen through Cytochrome P450. Does it convert through both of these pathways, and if so, what is the generally known rate of conversion?


Also, over on Ergo-Log's steroid handbook, they have the following quote:

21. The Real Anabolic Steroids

In principle nandrolone can aromatize, but this happens only under special circumstances and in small amounts. The normal aromatization of androstanes with the enzyme aromatase can not take place in nandrolone because the 19-methyl group is absent. Other enzymes have to oxidize ring A (remove two hydrogen atoms at C1 and C10) and then, after enolization of the C3-carbonyl group, the aromatic ring A is obtained.
Reduction of the D4 double bond by the enzyme 5AR can take place in a similar way as in testosterone. The androgenic activity of dihydronandrolone and its analogs is lower then that of the corresponding testosterone steroids. This means that less side effects occur in tissues where 5AR is active and converts nandrolone in dihydronandrolone. This results in a better ratio between anabolic and androgenic effects for nandrolone, in comparison with testosterone.

I was asking Anthony Roberts for his opinion about it, and he pointed me to the following study Rheumatology

which speculated that nandrolone completely suppresses testosterone and might fully cause estrogen production to cease, which I'm a bit skeptical about.

An RCT of the anabolic steroid nandrolone in 21 men with idiopathic osteoporosis showed an increase in bone density after 3 months of treatment, which decreased to basal levels after 1 yr of treatment [17]. The apparent lack of benefit with nandrolone may be related to suppression of endogenous testosterone production and the inability to aromatize anabolic steroids such as nandrolone to oestradiol.

Theories, speculation, conjecture and confusion are welcome. Thanks in advance,
pogue

 

[That_TRT_Guy]

mhhmm soo
Ethinylestradiol from norethisterone
Norethynodrel and 7 alpha-methyl-ethinylestradiol from tibolone



Traditional aromatase involves two separate enzymes:
CYParom acts as the catalyst oxidizing a 1 carbon androgen molecule at the 19-carbon points
NADPH-cytochrome P450 reductase removes the 19-carbon and create a new phenolic A-ring (part of estrogen)

Nandrolone is said to aromatizes at a rate of 18% of testosterone or androstenediol..
Nandrolone being a 19-nor, lacking the 19-carbon which CYParom acts upon, does not aromatization in the traditional sense. Instead Nandrolone aromatizes at the liver:
Liver based CYP 450 monooxygenase, degrades the 2-carbon of the nandrolone and creates the phenolic A-ring…the definitive step in converting an androgen (or 19-norandrogen in this case) into an estrogen.

i would assume that the
since the cytochrome P450 aromatase is not necessary and the A-ring can be catalyzed by available liver stored cytochrome P450 enzymes.
Standard Nandrolone would also follow the same pathway?

 

[pogue]

mhhmm soo
Ethinylestradiol from norethisterone
Norethynodrel and 7 alpha-methyl-ethinylestradiol from tibolone



Traditional aromatase involves two separate enzymes:
CYParom acts as the catalyst oxidizing a 1 carbon androgen molecule at the 19-carbon points
NADPH-cytochrome P450 reductase removes the 19-carbon and create a new phenolic A-ring (part of estrogen)

Nandrolone is said to aromatizes at a rate of 18% of testosterone or androstenediol..
Nandrolone being a 19-nor, lacking the 19-carbon which CYParom acts upon, does not aromatization in the traditional sense. Instead Nandrolone aromatizes at the liver:
Liver based CYP 450 monooxygenase, degrades the 2-carbon of the nandrolone and creates the phenolic A-ring…the definitive step in converting an androgen (or 19-norandrogen in this case) into an estrogen.

i would assume that the
since the cytochrome P450 aromatase is not necessary and the A-ring can be catalyzed by available liver stored cytochrome P450 enzymes.
Standard Nandrolone would also follow the same pathway?

That's a very detailed answer and very interesting. I hate to ask, but do you have any sources to back that up or documentation on nandrolone pharmacology. I'm having a very hard time trying to look for the conversion rate of nandrolone to estrogen and the where/when and how much in any kind of scientific literature. As I mentioned in my initial post, they have some interesting info on 19nor based progesterone birth control, but nothing specific to nandrolone.

 

[That_TRT_Guy]

That's a very detailed answer and very interesting. I hate to ask, but do you have any sources to back that up or documentation on nandrolone pharmacology. I'm having a very hard time trying to look for the conversion rate of nandrolone to estrogen and the where/when and how much in any kind of scientific literature. As I mentioned in my initial post, they have some interesting info on 19nor based progesterone birth control, but nothing specific to nandrolone.

iv simply read 18-20 % on various thread through time...


the pharmacology is in the text your provided,
However, 19-nortestosterone derivatives are characterized by the lack of the C19-methyl group. Therefore, for the aromatization of these synthetic steroids, the action of the cytochrome P450 aromatase is not necessary and the oxidative introduction of double bonds into the A-ring can be catalyzed by other hepatic cytochrome P450 enzymes. The final key process in the formation of a phenolic A-ring, both in natural androgens and 19-nortestosterone derivatives, is the enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety, which occurs without the action of enzymes. (end text)

the study is on various derivitives of the parent hormone Nandrolone, they all are 19 nor
i am assuming that since the study state the all that is need for Liver based CYP P450 monooxygenase start the creation of the phenolic A-ring via enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety is the lack of the c19 methly group...which i believe is another way of denoting 19-nor (they both mean lacking a carbon in the 19th position of the chain)

I beleive Nandrolone or 19-nortestosterone, lacking the Carbon in the 19th postion would be subject to the same enzymatic reaction
Testestosterone without the19th chain carbon =Nandrolone or 19-nortestosterone
19-nortestosterone means no 19C.
no 19c + CYP P450 monooxygenase = enolization of a 3-keto group into C2-C3-enol or C3-C4-enol = creation of phenol A ring which is the base of estrogen that attaches to the receptor site.

 

[That_TRT_Guy]

Perhaps Patrick Arnold would have some insight, i believe in a recent interview he mention messing with various derivatives off hours in his work lab lol

In general he is quite well versed in AAS, DS ,PH pharmacology

 

[pogue]

iv simply read 18-20 % on various thread through time...[snip]

This is getting into an area of chemistry that I am simply not familiar, so you'll have to forgive my lack of understanding. The problem is I'm writing an article, and I need to cite sources for where these numbers come from. So, if you have any recollection of where you saw them, let me know and I will try hunting them down.

I think my main non-technical question would be (and I apologize if you answered this and I simply didn't understand) is when and what causes nandrolone to convert via the aromatase enzyme and when and what causes it to convert via P450 - if there is any way of knowing. There is a theory that estrogen "lubricates" the joints of its user and makes workouts more pain free, and I am wondering if this is simply broscience or if there is something to it.

Obviously, this is a very complicated topic and I can see you are much more well versed in chemistry than I am, but I am also trying to take these complex explanations and explain them to the lay person so they know when and what to do about it. I am under the presumption that Nolvadex would take care of the majority of the negative estrogenic side effects with nandrolone, since if it's converting to estrogen via P450 in the liver and aromatase inhibitor would have no effect on it.

Perhaps Patrick Arnold would have some insight, i believe in a recent interview he mention messing with various derivatives off hours in his work lab lol

In general he is quite well versed in AAS, DS ,PH pharmacology

I have been trying to get ahold of him for some time actually, but he's a hard man to track down. There are a lot of old timers I would like to talk to about what's going on in the scene currently, including William Llewellyn, Par Deus, Dante, PA, David Tolson, and many others. But I'm afraid they've moved on to bigger and better projects and don't have much time for us anymore. However, if you happen to know any of their contact information, feel free to PM it to me and I'll do my best.

Thanks so much for your help, it's very much appreciated.

 

[That_TRT_Guy]

This is getting into an area of chemistry that I am simply not familiar, so you'll have to forgive my lack of understanding. The problem is I'm writing an article, and I need to cite sources for where these numbers come from. So, if you have any recollection of where you saw them, let me know and I will try hunting them down.

I think my main non-technical question would be (and I apologize if you answered this and I simply didn't understand) is when and what causes nandrolone to convert via the aromatase enzyme and when and what causes it to convert via P450 - if there is any way of knowing. There is a theory that estrogen "lubricates" the joints of its user and makes workouts more pain free, and I am wondering if this is simply broscience or if there is something to it.

Obviously, this is a very complicated topic and I can see you are much more well versed in chemistry than I am, but I am also trying to take these complex explanations and explain them to the lay person so they know when and what to do about it. I am under the presumption that Nolvadex would take care of the majority of the negative estrogenic side effects with nandrolone, since if it's converting to estrogen via P450 in the liver and aromatase inhibitor would have no effect on it.

Thanks so much for your help, it's very much appreciated.

No problem,, but i am by no means a pro at this,,,, and i would try to check most of what im writing

Nolvadex or any AI that actively binds to the estrogen receptor site, effectively blocking the Phenolic A ring structure of estrogen which would have attached to the site from exhibiting its effects
HOWEVER there is the idea floating around that Nolvadex significantly up-regulates progesterone receptors
if read that "The Progesterone receptor is in fact up-regulated in response to Estrogen. Therefore, but when the Estrogen receptor is effectively blocked by Nolvadex in breast tissue, the Progesterone receptor will, as a result, down-regulate."

"what causes nandrolone to convert via the aromatase enzyme "
When you say aromatase enzyme i assume you are talking about 5a reductase? it doesnt use 5a reductase.


FOr traditional natural 19C steroids ....steroids taht do have a carbon in the 19th spot
cytochrome P450 & 5a reductase enzymes convert C19 steroids, testosterone and androstenedione, into estradiol-17beta and estrone is dependent on the oxidative elimination of the angular C19-methyl group. This complex key reaction is catalyzed by the cytochrome P450 aromatase,

cytochrome P450 & 5a reductase enoliate (turning a keto in a enol) the 3-keto group into the C2-C3-enol or the C3-C4-enol moiety

so in natural steroids like TEST "5α-reductase act on 3-oxo (3-keto), Δ4,5 C 19/C21 steroids as its substrates. “3-keto” refers to the double bond of the third carbon to oxygen" which allows the creation of the Phenol ring=estrogen

"what causes it to convert via P450 "
In artificial 19 nor steroids (steroids without the carbon in the 19th position ) such as nandralone
Liver based CYP P450 monooxygenase start the creation of the phenolic A-ring via enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety is the lack of the c19 methly group...

so both 19C steroids like Test & 19nor (without the carbon in the 19th) like NANDROLONE both as some point start the creation of the phenolic A-ring (estrogen)via enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol

so.. i believe
TEST uses:
CYP P450
↓↓↓↓↓
enolization of a 3-keto group
↓↓↓↓↓
C2-C3-enol or C3-C4-enol
↓↓↓↓↓↓
creation of phenol A ring which is the base of estrogen that attaches to the receptor site.


NANDROLONE uses;
liver bases CYP P450 monooxygenase
↓↓↓↓↓
enolization of a 3-keto group
↓↓↓↓↓
C2-C3-enol or C3-C4-enol
↓↓↓↓↓↓
creation of phenol A ring which is the base of estrogen that attaches to the receptor site.

 

[pogue]

No problem,, but i am by no means a pro at this,,,, and i would try to check most of what im writing

Nolvadex or any AI that actively binds to the estrogen receptor site, effectively blocking the Phenolic A ring structure of estrogen which would have attached to the site from exhibiting its effects
HOWEVER there is the idea floating around that Nolvadex significantly up-regulates progesterone receptors
if read that "The Progesterone receptor is in fact up-regulated in response to Estrogen. Therefore, but when the Estrogen receptor is effectively blocked by Nolvadex in breast tissue, the Progesterone receptor will, as a result, down-regulate."

I'll have to look into that. It shouldn't matter that much, since progesterone isn't going to cause gyno without the presence of estrogen. But some have made the case for Clomid in place of Nolvadex for various reasons, but I believe being an antagonist at the ER is going to negate the effects of it entirely, making the whole thing null and void.

"what causes nandrolone to convert via the aromatase enzyme "
When you say aromatase enzyme i assume you are talking about 5a reductase? it doesnt use 5a reductase.

No, I realize that 5AR is a completely different mechanism. I guess what I'm asking is sort of fundamentally what causes the body to determine whether or not to convert one substance into another. Is there some sort of reason or logic behind it?

For example, lets say you're injecting 500mg a week of testosterone. Some of that testosterone is going to get converted to estrogen and some will get converted to DHT. Why, specifically does this happen? Does the body see a need for extra DHT somewhere and pass the testosterone to the 5AR receptor or does the 5AR receptor just get overwhelmed with extra testosterone so the process starts regardless? The same with estrogen. Obviously a male has little need of estrogen, so what triggers testosterone to convert to estrogen -- not in a chemical sense, but in a biological or physiological sense, if that makes any sense.

This might be heading into kind of an esoteric discussion that has no basis in reality, so I don't know if that makes any sense to you, but that's always been a curious point to me. What is the triggering mechanism that tells the enzymes to convert testosterone to estrogen, or just leave it as testosterone and let it circulate, attach to the androgen receptor and do its thing.

 

[That_TRT_Guy]

I'll have to look into that. It shouldn't matter that much, since progesterone isn't going to cause gyno without the presence of estrogen. But some have made the case for Clomid in place of Nolvadex for various reasons, but I believe being an antagonist at the ER is going to negate the effects of it entirely, making the whole thing null and void.



No, I realize that 5AR is a completely different mechanism. I guess what I'm asking is sort of fundamentally what causes the body to determine whether or not to convert one substance into another. Is there some sort of reason or logic behind it?

For example, lets say you're injecting 500mg a week of testosterone. Some of that testosterone is going to get converted to estrogen and some will get converted to DHT. Why, specifically does this happen? Does the body see a need for extra DHT somewhere and pass the testosterone to the 5AR receptor or does the 5AR receptor just get overwhelmed with extra testosterone so the process starts regardless? The same with estrogen. Obviously a male has little need of estrogen, so what triggers testosterone to convert to estrogen -- not in a chemical sense, but in a biological or physiological sense, if that makes any sense.

This might be heading into kind of an esoteric discussion that has no basis in reality, so I don't know if that makes any sense to you, but that's always been a curious point to me. What is the triggering mechanism that tells the enzymes to convert testosterone to estrogen, or just leave it as testosterone and let it circulate, attach to the androgen receptor and do its thing.

bio logically the body has a predetermined E to T ratio...and it tries to stay within that realm....so if you sky rocket your T your will try to achieve that ratio again..

its different for everyone

 

[criticalbench]

Legit thread.. Plan to read in full!

 

[That_TRT_Guy]

Legit thread.. Plan to read in full!

plz critique iof you can ..i am a chem noob at the end of the day,, so the more the merrier

 

[brofessorx]

henryv

 

[pogue]

bio logically the body has a predetermined E to T ratio...and it tries to stay within that realm....so if you sky rocket your T your will try to achieve that ratio again..

its different for everyone

Did you mean testosterone and epitestosterone or estrogen?

Makes sense, but what about DHT and other anabolics? Is there some kind of DHT ratio?

Then what about prolactin, progesterone, and things like that? Is there some kind of trigger that causes those things to get released?

And what about exotic and novel AAS that aren't based around testosterone, like nandrolone just for example. If the body is trying to maintain a T:E ratio, what happens when you add nandrolone into the mix? If you used that alone and it suppressed testosterone, would estrogen naturally lower just by trying to maintain the ratio? I could think of a lot of other exotic examples of AAS that don't convert to testosterone or DHT (I'm kind of just thinking out loud here) and what exactly occurs when you're supplementing with those compounds and how the body's homeostasis tries to resolve itself other than the negative feedback of naturally suppressing testosterone levels.

 

[pogue]

Ok, I think I found the answer. However, the PDF for the study is copy protected or something and I can't copy and paste the text. So, I saved the relevant paragraph as an image.

Here is the link to the study http://www.ncbi.nlm.nih.gov/pubmed/11732643

 

[BeastFitness]

Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage.

Family 19 of the P450 super family is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization because it involves conversion of the delta4-3-one A-ring of the androgens to the corresponding phenolic A-ring characteristic of estrogens. The gene encoding human aromatase has been cloned and characterized and shown to be unusual compared to genes encoding other P450 enzymes, because there are numerous untranslated first exons that occur in aromatase transcripts in a tissue-specific fashion due to differential splicing as a consequence of the use of tissue-specific promoters. Thus, expression in the ovary uses a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in the placenta uses a distal promoter located at least 40 kb upstream of the start of transcription that is regulated by retinoids. Other promoters are used in brain and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11, as well as TNF-alpha, are important regulatory factors. A common 3'-splice junction located upstream of the start of translation is used in all of the splicing events involved in the use of these various promoters. Thus, the coding region of the transcripts, and hence the protein, are identical regardless of the tissue site of expression; what differs in a tissue-specific fashion is the 5'-end of the transcripts. This pattern of expression has great significance both from a phylogenetic and ontogenetic standpoint, as well as for the physiology and pathophysiology of estrogen formation, as will be discussed in this review.

http://www.ncbi.nlm.nih.gov/pubmed/9034163


A review of brain aromatase cytochrome P450

Aromatase cytochrome P450 (P450AROM) enzyme activity catalyzes the conversion of androgens to estrogens in specific brains areas. During central nervous system development local estrogen formation influences the sexual differentiation of neural structures (i.e., by increasing neurite growth and establishing neural circuitry) and modulates neuroendocrine/reproductive functions and sexual behavior. More than 20 years ago, in 1970, Naftolin et al. provided preliminary direct evidence for the aromatization of androgens by central neuroendocrine tissues. This work created the foundation for the brain aromatase hypothesis. A review of past and recent data reveals the importance of brain aromatase in the development and function of the central nervous system. This review re-examines the aromatase hypothesis in light of recent data and a theoretical proposal is presented in reference to the aromatase mechanism. The metabolic pathway of androgen metabolism by the aromatase cytochrome P450 pathway, cell type, distribution, developmental profile, and regulation of brain aromatase is also presented. The complex nature of brain aromatase is exemplified by recent molecular biology studies examining the expression of aromatase cytochrome P450 during prenatal/postnatal development. Data derived from these studies provide insight into the regulation of the brain aromatase cytochrome P450 gene and suggest an additional level of control for the expression of brain aromatase. These findings present evidence for the utilization of alternative promoter(s) in man and rodents in driving aromatase gene expression in brain. It is clear that molecular mechanism(s) account for the diverse expression of aromatase in different neural tissue sites and during various physiological states or developmental periods. Therefore, further study is necessary in order to understand the significance of the regulation of local estrogen biosynthesis by the aromatase cytochrome P450 gene during prenatal and postnatal development due to the dramatic impact these estrogen molecules have on neural development and their influence on reproductive function and behavior.


http://www.sciencedirect.com/science/article/pii/0165017396000021

 

[That_TRT_Guy]

NOTE: Its responsible for converting C19 steroids...meaning steroids with carbon in the 19th position.......nandrolone is 19-nor...meaning there is not carbon in the 19 position to by oxidative elimination of the angular C19-methyl group: the
enolization (turning a keto in a enol) of the 3-keto group into the C2-C3-enol or the C3-C4-enol moiety which allows the creation of the Phenol ring=estrogen

 

[pogue]

Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage.

Family 19 of the P450 super family is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization because it involves conversion of the delta4-3-one A-ring of the androgens to the corresponding phenolic A-ring characteristic of estrogens. The gene encoding human aromatase has been cloned and characterized and shown to be unusual compared to genes encoding other P450 enzymes, because there are numerous untranslated first exons that occur in aromatase transcripts in a tissue-specific fashion due to differential splicing as a consequence of the use of tissue-specific promoters. Thus, expression in the ovary uses a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in the placenta uses a distal promoter located at least 40 kb upstream of the start of transcription that is regulated by retinoids. Other promoters are used in brain and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11, as well as TNF-alpha, are important regulatory factors. A common 3'-splice junction located upstream of the start of translation is used in all of the splicing events involved in the use of these various promoters. Thus, the coding region of the transcripts, and hence the protein, are identical regardless of the tissue site of expression; what differs in a tissue-specific fashion is the 5'-end of the transcripts. This pattern of expression has great significance both from a phylogenetic and ontogenetic standpoint, as well as for the physiology and pathophysiology of estrogen formation, as will be discussed in this review.

http://www.ncbi.nlm.nih.gov/pubmed/9034163

No idea what this means or how it relates to the discussion of nandrolone conversion to estrogen.

A review of brain aromatase cytochrome P450

Aromatase cytochrome P450 (P450AROM) enzyme activity catalyzes the conversion of androgens to estrogens in specific brains areas. During central nervous system development local estrogen formation influences the sexual differentiation of neural structures (i.e., by increasing neurite growth and establishing neural circuitry) and modulates neuroendocrine/reproductive functions and sexual behavior. More than 20 years ago, in 1970, Naftolin et al. provided preliminary direct evidence for the aromatization of androgens by central neuroendocrine tissues. This work created the foundation for the brain aromatase hypothesis. A review of past and recent data reveals the importance of brain aromatase in the development and function of the central nervous system. This review re-examines the aromatase hypothesis in light of recent data and a theoretical proposal is presented in reference to the aromatase mechanism. The metabolic pathway of androgen metabolism by the aromatase cytochrome P450 pathway, cell type, distribution, developmental profile, and regulation of brain aromatase is also presented. The complex nature of brain aromatase is exemplified by recent molecular biology studies examining the expression of aromatase cytochrome P450 during prenatal/postnatal development. Data derived from these studies provide insight into the regulation of the brain aromatase cytochrome P450 gene and suggest an additional level of control for the expression of brain aromatase. These findings present evidence for the utilization of alternative promoter(s) in man and rodents in driving aromatase gene expression in brain. It is clear that molecular mechanism(s) account for the diverse expression of aromatase in different neural tissue sites and during various physiological states or developmental periods. Therefore, further study is necessary in order to understand the significance of the regulation of local estrogen biosynthesis by the aromatase cytochrome P450 gene during prenatal and postnatal development due to the dramatic impact these estrogen molecules have on neural development and their influence on reproductive function and behavior.


http://www.sciencedirect.com/science/article/pii/0165017396000021

Tbh, this sounds more like something that would happen during brain development during childhood and adolescence than in adults. But, even if estrogen is being converted in the brain to some degree, it's not going to be responsible for gyno or the other negative effects we associate with estrogen.

NOTE: Its responsible for converting C19 steroids...meaning steroids with carbon in the 19th position.......nandrolone is 19-nor...meaning there is not carbon in the 19 position to by oxidative elimination of the angular C19-methyl group: the
enolization (turning a keto in a enol) of the 3-keto group into the C2-C3-enol or the C3-C4-enol moiety which allows the creation of the Phenol ring=estrogen

I have absolutely no idea what you just said Can you explain in layman's terms?

 

[That_TRT_Guy]

No idea what this means or how it relates to the discussion of nandrolone conversion to estrogen.




Tbh, this sounds more like something that would happen during brain development during childhood and adolescence than in adults. But, even if estrogen is being converted in the brain to some degree, it's not going to be responsible for gyno or the other negative effects we associate with estrogen.




I have absolutely no idea what you just said Can you explain in layman's terms?

all of that is only in regards to 19C steroids like TEST.....

 

[pogue]

all of that is only in regards to 19C steroids like TEST.....

So Nandrolone is missing the carbon at the 19th position. So, my quote is entirely incorrect. *Sigh* Well, back to the drawing board I guess.

Obviously my chemistry skills suck, but can you break down for me what the chemical attributes of nandrolone are?

Here is the molecule.

And then here is a 4 carbon atom steroid skeleton

(I'm trying to find a better picture showing the c19 position but I can't find a good one).

 

[That_TRT_Guy]

you will never find a better picture of those carbons on a nandrolone molecule, because they are not there