Breast Growth For Genetic Males

@ Lotus....


[img]http://i0.kym-cdn.com/photos/images/newsfeed/000/173/576/Wat8.jpg[/img

Hello (= hope all are doing well!!!

I have a question for you, Lotus =D hope you're available =]]

I remember months ago you recommending to take evening primrose oil as an aromatase and pumpkin seed oil as an anti-androgen (both in the capsule form).

i have been taking them religiously as recommended, sometimes upping the doses, sometimes lowering them. I'm wondering, should I take time off and stop them all together? I'm on my PM break for maybe another month or 2 btw. are these supplements any different from taking say a multi vitamin or biotin, etc. do you have to stop taking them from time to time?

Right now i'm taking: multivitamin, Evening P.O., Pumpkin S.O., biotin, magnesium, B-complex. Do you recommend I stop any or keep everything going? (minus the PM, i know you need breaks with that one, which i'm one)

i know ur not a Dr or anything, but i feel u give the most soundest and clearest and most helpful advise tbh! hope you can help!!! Much love!!

Good luck to you on your progress xoxo

Hi , I'm new to this so bear with me....
I just want some advice as there is so many conflicting opinions my head is frazzled.
I started taking pm on the first day of cycle last month and took it for 15 days. 1000mg a day (Although I had been taking 500 a day a fortnight prior to starting my period to get my body used to it)
I was clearly taking to much as had blurred vision, lighthead and palpitations.
I stopped after 15 days however my period is now 4 days late...

Am I best to continue like I was on the first day of my next period or change it to what others have suggested and start taking it after my period for 15 days??

I am scared to say this as I have seen some people getting g slack for it but yup it's ainterol pure d 500 that I took! Don't judge me. Haha.
This was the 3rd batch I bought after buying 2 others which were not pure.
What is everyone else's opinion on when I should restart the pm.
I am 35 and just want fullness in my bust as after having my daughter and coming of the pill which I had been on for 17 years the lack of oestrogen in my body has seen my chest deflate and flop greatly which is causing me great distress and loads of paranoia issues...
Any nice advice would be great
xx

(24-03-2015, 08:14 AM)34TripleD Wrote: [ -> ]Hello (= hope all are doing well!!!

I have a question for you, Lotus =D hope you're available =]]

I remember months ago you recommending to take evening primrose oil as an aromatase and pumpkin seed oil as an anti-androgen (both in the capsule form).

i have been taking them religiously as recommended, sometimes upping the doses, sometimes lowering them. I'm wondering, should I take time off and stop them all together? I'm on my PM break for maybe another month or 2 btw. are these supplements any different from taking say a multi vitamin or biotin, etc. do you have to stop taking them from time to time?

Right now i'm taking: multivitamin, Evening P.O., Pumpkin S.O., biotin, magnesium, B-complex. Do you recommend I stop any or keep everything going? (minus the PM, i know you need breaks with that one, which i'm one)

i know ur not a Dr or anything, but i feel u give the most soundest and clearest and most helpful advise tbh! hope you can help!!! Much love!!

Good luck to you on your progress xoxo

Hi 34,

EPO should've given you swelling, help elimate DHT and help synthesize aromatase. Biotin will also help with FAS (fatty acid synthase). Omega 3's will help reduce inflammation, if you've got too much omega 6's you'll see (or get) unnecessary inflammatory response. Too much PGE2 (prostaglandin) in response from inflammation pushes this response ratio, in other words.....stop growth potential.

Imo balance the omegas, (stop the EPO for 2 weeks) add in omega 3 (chia seeds) 2-3 grams daily. After 2 weeks add coconut oil, 1-2 tablespoons daily. Drop the PSO, there's enough 5 ar inhibitor in EPO once you add it back.

I think you have the right components, it's just missing a few essentials, (e.g. growth hormone). Here's what I mean:

Effects of growth hormone on adipose tissue.

Abstract
Physiological effects of growth hormone (GH) extend beyond the stimulation of linear growth. These include important metabolic effects upon adipose tissue. GH affects both proliferation and differentiation of preadipocytes, although this varies between clonal cell lines and preadipocyte cultures. Both preadipocytes and mature adipocytes possess specific GH receptors. GH may mediate its actions via these receptors, but some effects are indirectly mediated through the GH-mediated secretion of insulin-like growth factor-I (IGF-I) within adipose tissue. GH promotes lipolysis via inhibition of lipoprotein lipase, which hydrolyzes triglycerides in the circulation to make them available for triglyceride accumulation in adipose tissue. GH also stimulates hormone sensitive lipase (HSL), the rate-limiting step for release of stored triglyceride in adipocytes (lipolysis). As GH becomes utilized for various "non-growth" concerns (see Figure 1), awareness of the metabolic effects on adipocytes is important to understand the clinical effects seen with GH therapy.
http://www.ncbi.nlm.nih.gov/pubmed/11086655

_______________________

This website below gives an excellent summary on how to go about proceeding:

Stimulating the Body’s Production of Human Growth Hormone
http://www.bodybuildingforyou.com/articl...uction.htm

I'll post other info on inducible nitric oxide synthase, and how it modulates lipolysis in adipocytes (The basis for building breast tissue), really interesting stuff.
------------------------


iaboy and gamer, what's (a) the simple explanation of inactivating DHT?, (i dunno) picture a free loading uncle named DHT, hey lol, work with me! .....all he does is sponge off you...eats you out of house and home.......solution.....drop kick his ass to the curb while he's sleeping...(oh yeah!!, you forgot to tell him it's also trash day).

Now he's......I-N-A-C-T-I-V-E (sorry, it's the best I got today).

I understand what inactivate means, but I am no chemist. Which, if any, herb or supplement will do this w/out running serious risk?

(24-03-2015, 05:55 PM)Lotus Wrote: [ -> ]Hi 34,

EPO should've given you swelling, help elimate DHT and help synthesize aromatase. Biotin will also help with FAS (fatty acid synthase). Omega 3's will help reduce inflammation, if you've got too much omega 6's you'll see (or get) unnecessary inflammatory response. Too much PGE2 (prostaglandin) in response from inflammation pushes this response ratio, in other words.....stop growth potential.

Imo balance the omegas, (stop the EPO for 2 weeks) add in omega 3 (chia seeds) 2-3 grams daily. After 2 weeks add coconut oil, 1-2 tablespoons daily. Drop the PSO, there's enough 5 ar inhibitor in EPO once you add it back.

I think you have the right components, it's just missing a few essentials, (e.g. growth hormone). Here's what I mean:

Effects of growth hormone on adipose tissue.

Abstract
Physiological effects of growth hormone (GH) extend beyond the stimulation of linear growth. These include important metabolic effects upon adipose tissue. GH affects both proliferation and differentiation of preadipocytes, although this varies between clonal cell lines and preadipocyte cultures. Both preadipocytes and mature adipocytes possess specific GH receptors. GH may mediate its actions via these receptors, but some effects are indirectly mediated through the GH-mediated secretion of insulin-like growth factor-I (IGF-I) within adipose tissue. GH promotes lipolysis via inhibition of lipoprotein lipase, which hydrolyzes triglycerides in the circulation to make them available for triglyceride accumulation in adipose tissue. GH also stimulates hormone sensitive lipase (HSL), the rate-limiting step for release of stored triglyceride in adipocytes (lipolysis). As GH becomes utilized for various "non-growth" concerns (see Figure 1), awareness of the metabolic effects on adipocytes is important to understand the clinical effects seen with GH therapy.
http://www.ncbi.nlm.nih.gov/pubmed/11086655

_______________________

This website below gives an excellent summary on how to go about proceeding:

Stimulating the Body’s Production of Human Growth Hormone
http://www.bodybuildingforyou.com/articl...uction.htm

I'll post other info on inducible nitric oxide synthase, and how it modulates lipolysis in adipocytes (The basis for building breast tissue), really interesting stuff.
------------------------


iaboy and gamer, what's (a) the simple explanation of inactivating DHT?, (i dunno) picture a free loading uncle named DHT, hey lol, work with me! .....all he does is sponge off you...eats you out of house and home.......solution.....drop kick his ass to the curb while he's sleeping...(oh yeah!!, you forgot to tell him it's also trash day).

Now he's......I-N-A-C-T-I-V-E (sorry, it's the best I got today).

Thank you oh so very much for responding Lotus!!!!! xoxox

I will stop the PSO altogether, and go on a break w/ EPO, and switch over to chia seeds & coconut oil like you said!!

I do work out on a consistent basis, get my veggies and sleep like that article said for the Growth Hormone....not sure if there is a vitamin/supplement that will help.... i'll just start PM again in a couple of months ..seems like the best GH lol (=

thanks again!!! <3

Hi Lotus, here I am
This is another paper about palmitoylation:

Palmitoylation regulates 17β-estradiol-induced estrogen receptor-α degradation and transcriptional activity.
http://www.ncbi.nlm.nih.gov/pubmed/22446104

[...]
The lack of palmitoylation renders ERα more susceptible to E2-dependent degradation, blocks ERα S118 phosphorylation and prevents E2-induced ERα estrogen-responsive element-containing promoter occupancy. Consequently, ERα transcriptional activity is prevented and the receptor addressed to the nuclear matrix subnuclear compartment. These data uncover a circuitry in which receptor palmitoylation links E2-dependent ERα degradation, S118 phosphorylation, and transcriptional activity in a unique molecular mechanism. We propose that rapid E2-dependent signaling could be considered as a prerequisite for ERα transcriptional activity and suggest an integrated model of ERα intracellular signaling where E2-dependent early extranuclear effects control late receptor-dependent nuclear actions.

ok palmitoylation is good for a good estrogen activity, you ask: "the palmitoylation of estrogen receptor alpha (ER-a) is (or can be) mediated by oxidative phosphorylation?"
my answer is: I don't know...what do you mean?

Oxidative phosphorylation, wiki (not my favourite source, but this time i can use it):
Oxidative phosphorylation (or OXPHOS in short) is the metabolic pathway in which the mitochondria in cells use their structure, enzymes, and energy released by the oxidation of nutrients to reform ATP. Although the many forms of life on earth use a range of different nutrients, ATP is the molecule that supplies energy to metabolism. Almost all aerobic organisms carry out oxidative phosphorylation.[...]. Although oxidative phosphorylation is a vital part of metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide, which lead to propagation of free radicals, damaging cells and contributing to disease and, possibly, aging (senescence). The enzymes carrying out this metabolic pathway are also the target of many drugs and poisons that inhibit their activities.


in the paper above, it says: These E2 rapid effects require a population of the ERα located at the cell plasma membrane through palmitoylation, a dynamic enzymatic modification mediated by palmitoyl-acyl-transferases.

We should find how this enzyme palmitoyl-acyl-transferases works, if you want to gain estrogen activity (and maybe is not enough, as you see our bodies are quite complicated... )
indeed from your link: "E2 reduces both ERalpha palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner"
So, if you want you can increase estrogen receptor expression, but there is a negative feedback as well from estradiol. This is good for the body, to regulate his pathways....and try to keep some equilibrium. We just want to move some of it to favor breast growth, and if estrogen receptor is stronger than negative feedback of estradiol, than it should be worthy the way of palmitoylation.

I think the best way to try to gain some breast is in my previous link, and you noticed that: we should just low the androgen activity in breast, to have breast growth. This is quite simpler than taking account of all the other biological pathways, that's why i started from that (anyway, everything is important, also estrogen, and food, and enzymes.... but i think that the king to fight here is DHT)
I didn't know about DHT metabolites, my thoughs are: if DHT (and metabolite) is more androgenic, then estrogenic in breast tissue, than it could be helpful low it.

Lotus Wrote:I'm sure you're aware that fatty acids synthesize aromatase, (what are your thoughts?)."

ehm... nope. I'm just a scientist, not omniscient :-P
i didn't find this before. I read something on your A.A. thread, but now i missed it. Could you link some source? I tried to have a look but i couldn't find much.
Then i will tell you what I think, but for sure, if fatty acids can promote aromatase expression, that would be great!

Lotus Wrote:"On another note....I've seen that EPA and DHA reduces the risk of breast cancer by as much as a 32% reduction, I don't know the dosage."

Where did you see that? which paper? i quickly had a look on the one you linked before, but i didn't find that information

-Clelia- Wrote:thank you Lotus, I'm ready to go. Happy me!
yep you gave to a scientist a good homework

Lotus Wrote:Did i?..... cool, I thought I might have insulted you lol.

no worries, of course not

-Clelia- Wrote:How come, am I the only one? Where are all the others? There is a lot of people here.

Lotus Wrote:Don't know....but I'm glad you're here. I have all kinds of crazy ideas and only myself to entertain them, lmao."

eheh, i'm glad as well, but there is other people that contributed sometimes. Anyway I understand the way you feel. I'm crazy almost like you, and i like scientific research, so I can make good company (Imao)

-Clelia- Wrote:Anyway, you could be a scientist.

Lotus Wrote:You think so?, nah....... I'm not worthy although I'd love to be one. and thank you so much for saying so.

Your knowledge is becoming huge, also you research a lot, so there is no big difference between you and a scientist. You could apply to a University if you wanted.

Finally, could you help me? I'm looking information for "bad estrogen" that make growth faster,
what is its name? I saw it somewhere but I don't remember.
Thank you very much
See you,
bye!

have a look at this also:

http://joe.endocrinology-journals.org/co...0.full.pdf

good one Lotus, leucine is an essential aminoacid, and also I see that promote ERalfa. Food is very important

Hi Clelia,

It's nice to hear from you again, it's truly an honor and inspiration hearing your comments, it takes my breath away. Tbh, when I research the reward is finding anything that remotely benefits breast growth and overall health. Time after time science/research continually takes my breath away. It's like finding your first love , albeit in an abstract lol.....(does that sound craZy?) lol.......ok, that's probably over the top, buts it's something in that order. Im my case your never to old to rediscover my potential......

(24-03-2015, 11:15 PM)-Clelia- Wrote: [ -> ]Finally, could you help me? I'm looking information for "bad estrogen" that make growth faster

Sure, my pleasure.....

Those E metabolites are 16α-OH estrone & 2-OH estrone, I list this study below from 2008, it's pretty interesting, the findings are different from what I've seen.

[These data do not support the hypothesized inverse associations with 2-OH estrone and the 2:16α-OH estrone ratio nor the hypothesized positive association with 16α-OH estrone].

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast cancer among postmenopausal women
----------------------
Abstract

Circulating estrogens are associated with breast cancer risk in postmenopausal women. Given that estrogen metabolites are potentially both mitogenic and genotoxic, it is possible that plasma levels of estrogen metabolites are related to breast cancer risk. We conducted a prospective, nested case- control study within the Nurses' Health Study. Blood samples, collected in 1989-1990, were assayed for 2-OH estrone and 16α-OH estrone among 340 cases and 677 matched controls not taking postmenopausal hormones. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for breast cancer risk factors. Neither 2-OH estrone nor 16α-OH estrone concentrations were significantly associated with breast cancer risk overall (top vs. bottom quartile RR=1.19, 95% CI (0.80-1.79), p-trend=0.40 for 2-OH estrone and RR=1.04, 95% CI (0.71-1.53), p-trend=0.81 for 16α-OH estrone). The ratio between the two metabolites (2:16α-OH estrone) was similarly unrelated to risk overall (1.30, 95% CI (0.87-1.95), p- trend=0.35). While no associations were detected among women with ER+/PR+ tumors, significant positive associations were observed for 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors (2-OH estrone RR=3.65 95% CI (1.23-10.81), p-trend=0.01, p- heterogeneity=0.02; 2:16α-OH estrone RR=3.70, 95% CI (1.24-11.09), p-trend=0.004, p- heterogeneity=0.005). These data do not support the hypothesized inverse associations with 2-OH estrone and the 2:16α-OH estrone ratio nor the hypothesized positive association with 16α-OH estrone. The significant positive associations with 2-OH estrone and the 2:16 OH estrone ratio among women with ER-/PR- tumors needs to be replicated in future studies.

http://www.ncbi.nlm.nih.gov/pmc/articles...s52956.pdf
___________________________________

The following is model I'm trying to complete in my mind,

For instance--hormones diffuse across membranes, are ion channels the entry point??, ERE, ER, AR, PR exist in the same cell, can carrier proteins distinguish a preferential binding?, Dexamethasone is an aromatase, Palmitate is proteins in ER-a, assuming FA's can muscle their way into the cytoplasm, from there transcription?........ramblings of a lunatic lol, I get these screw ball ideas, sometimes they wake me from complete sleep...it's freaky.

Here's an example of that freakiness.

Lipoxygenases (EC 1.13.11.-) are a family of iron-containing enzymesthat catalyze the dioxygenation of polyunsaturated fatty acids in lipidscontaining a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:

fatty acid + O2 = fatty acid hydroperoxide

Lipoxygenases are found in plants, animals and fungi. Products of lipoxygenases are involved in diverse cell functions.



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

Quote:.[2] In mammals a number of lipoxygenases isozymes are involved in the metabolism of eicosanoids(such as prostaglandins, leukotrienes and nonclassic eicosanoids).[3] Sequence data is available for the following lipoxygenases:

compounds attack cell membranes and red blood cells, and they even cause damage to DNA and RNA strands, leading to cellular mutations in the body’s tissues. In skin, it causes wrinkles and premature aging. In blood vessels, the buildup of plaque. In tissues and organs, it can set the stage for tumors to form. I think you get the picture. Free radicals are bad, bad news, and they’re ever-present in industrial PUFA oils.
-----------------------

On a different note......

The TG (triglyceride) form of fish oil contains its own monoglyceride substrate; whereas EE fish oils, coupled to ethanol, do not. EE must therefore obtain a glycerol substrate from another source. Without a glycerol or monoglyceride substrate TG re-synthesis is delayed, suggesting that transport to the blood is more efficient in natural TG fish oils in comparison to EEs. Furthermore, this delay of TG re-synthesis in EE fish oils could cause an increase in free fatty acids and subsequent oxidation of those free fatty acids.

I'm gonna out on on limb here.....,I wonder if ethanol release stated below could be in part what converts to aromatase.

During the digestive process, EEs are converted back to TGs by intestinal enterocytes1 which, results in the release of ethanol. Although the amount of ethanol released in a typical dose of fish oil is small, those with sensitivities to alcohol or those who are alcoholics should refrain from the consumption of EEs.

Fish Oil Triglycerides vs. Ethyl Esters: A comparative review of absorption, stability and safety concerns
http://pi-bill-articles.blogspot.com/201...s.html?m=1

(Note-The above article is from a blog, I couldn't find any supported research, imo the perspective is eye opening (are all EFA supplements misidentified?, good grief.

(24-03-2015, 11:15 PM)-Clelia- Wrote: [ -> ]. but i think that the king to fight here is DHT)
I didn't know about DHT metabolites, my thoughs are: if DHT (and metabolite) is more androgenic, then estrogenic in breast tissue, than it could be helpful low it.

I just so happens , I know what you mean, and there is a back door to DHT.......

(23-03-2015, 09:00 PM)Lotus Wrote: [ -> ]

(22-02-2015, 07:53 PM)Lotus Wrote: [ -> ]From an earlier post,


DHT has an estrogenic action,

The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the major estrogen in males [29]. For instance, in the prostate there is a growing body of evidence that 3β-diol, acting through ERβ, may regulate important physiological events.


Recent data have shown that DHT may be converted into 5α-androstane- 3β-17β-diol (3β-diol) in a virtually irreversible reaction. Once considered inactive, 3β-diol is present in high concentrations in the male and indeed has biological activity. However, 3β-diol does not bind to the androgen receptor (AR), but rather to ERα and ERβ, with higher affinity for ERβ. Based upon these findings, we hypothesized that the modulation of AQP9 by DHT could be indirectly mediated by 3β-diol.

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

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615873/


Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects,

Abstract

Background: Fluid homeostasis is critical for normal function of the male reproductive tract and aquaporins (AQP) play an important role in maintenance of this water and ion balance. Several AQPs have been identified in the male, but their regulation is not fully comprehended. Hormonal regulation of AQPs appears to be dependent on the steroid in the reproductive tract region. AQP9 displays unique hormonal regulation in the efferent ductules and epididymis, as it is regulated by both estrogen and dihydrotestosterone (DHT) in the efferent ductules, but only by DHT in the initial segment epididymis. Recent data have shown that a metabolite of DHT, 5-alpha- androstane-3-beta-17-beta-diol (3-beta-diol), once considered inactive, is also present in high concentrations in the male and indeed has biological activity. 3-beta-diol does not bind to the androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the only estrogen to play a major role in the male reproductive system. Considering that both ER-alpha and ER-beta are highly expressed in efferent ductules, we hypothesized that the DHT regulation of AQP9 could be due to the 3-beta-diol metabolite.

Methods: To test this hypothesis, adult male rats were submitted to surgical castration followed by estradiol, DHT or 3-beta-diol replacement. Changes in AQP9 expression in the efferent ductules were investigated by using immunohistochemistry and Western blotting assay.

Results: Data show that, after castration, AQP9 expression was significantly reduced in the efferent ductules. 3- beta-diol injections restored AQP9 expression, similar to DHT and estradiol. The results were confirmed by Western blotting assay.

Conclusion: This is the first evidence that 3-beta-diol has biological activity in the male reproductive tract and that this androgen metabolite has estrogen-like activity in the efferent ductules, whose major function is the reabsorption of luminal fluids.





a) It has been shown that 3β-diol may have hormonal activity, not acting through the AR, but rather as a ligand for both ERα and ERβ.

b) 3β-diol has higher affinity for ERβ [31], which is abundant in the efferent ductule epithelium [40].

c) In human testis, the 3β-diol concentration is higher than DHT and estradiol [44,45]. It is reasonable to postulate that high concentrations of this metabolite may enter the lumen of efferent ductules.

d) The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the major estrogen in males [29]. For instance, in the prostate there is a growing body of evidence that 3β-diol, acting through ERβ, may regulate important physiological events [26,28,32,46].

Also noteworthy is the fact that 3β-diol stimulates ERβ induced transcriptional activity equal to the cognate ligand estradiol, and the transcriptional selectivity of 3β-diol for ERβ is much greater than its binding selectivity [30,46]

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


Concentrations of aromatase and estradiol in the prostate are low, indicating that estradiol may not be the only estrogenic molecule to play a role in the prostate. It is known that DHT can be metabolized to 5alpha-androstane-3beta,17beta-diol (3beta-diol), a hormone that binds to ERbeta but not to AR. The concentration of 3beta-diol in prostate is much higher than that of estradiol. Based on the high concentration of 3beta-diol and since this metabolite is a physiological ERbeta ligand, we hypothesized that 3beta-diol would be involved in the regulation of ERbeta expression.





An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.
http://www.ncbi.nlm.nih.gov/pubmed/12370428

I've spent more time researching on this backdoor estrogenic action of DHT, aka estrogen receptor beta. From what I see when DHT is metabolized in the liver we can force it to this ER-b back door, thereby lessening (or inactivating) it's potential. And imo cortisteriods inactivates DHT.

(23-03-2015, 09:31 PM)Lotus Wrote: [ -> ]

_____________________________________________

(07-02-2015, 08:33 AM)Lotus Wrote: [ -> ]

(13-01-2015, 07:44 PM)Lotus Wrote: [ -> ]It's like deconstructing a model (call it a airplane model) that someone else built, only you're working in reverse to deconstruct right. Same applies here, you see a study that states 5 alpha reductase is reduced in the liver, now maybe this study was for cancer research or something similar. Let's take one of these studies,

Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family, which are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

AKRs are involved in the development and progression of many cancers, as well as chemotherapeutic drug resistance. AKR1B1 and AKR1B10 are overexpressed in tumors, such as liver, breast, and lung cancer. Several AKRs (AKR1A1, AKR1B10, and AKR1C1-3) are involved in tobacco-carcinogenesis, but they also catalyze the detoxication of nicotine derived nitrosamino ketones. In addition, AKR1C1-3 enzymes play a key role in the regulation of proliferative signaling in hormone dependent cancers.

So what they did in this study was to cut off the androgen synthesis to the receptors using another steroid , Four human aldo-keto reductases (AKRs) that belong to the AKR1C subfamily function in vitro as 3-keto-, 17-keto- and 20-ketosteroid reductases or as 3alpha-, 17beta- and 20alpha- hydroxysteroid oxidases to varying degrees. By acting as ketosteroid reductases or hydroxysteroid oxidases these AKRs can either convert potent sex hormones (androgens, estrogens and progestins) into their inactive metabolites or they can form potent hormones by catalyzing the reverse reaction. In this manner they may regulate occupancy and trans-activation of steroid hormone receptors.

In English, I want to find the link to activate AKR1c in the liver to shut off the androgen receptors therefore DHT never gets activated, simple right?.

Cha-Ching, found it.

Regulates access of 5alpha-DHT to the androgen receptor.

Abstract
Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2, aka-AKR acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.
http://www.ncbi.nlm.nih.gov/pubmed/17223255

Notice how Aldo-keto reductases (AKRs) position themselves between DHT and 3-diols, this is where the estrogenic action takes place. These actions of AKR1C's takes place in androgen metabolism of the prostate.

Aldo-keto reductases (AKRs) is another superfamily class of enzymes like the Cytochrome P450 enzyme super family.






Estrogen receptor β and 17β-hydroxysteroid dehydrogenase type 6, a growth regulatory pathway that is lost in prostate cancer

Estrogen receptor β (ERβ) is activated in the prostate by 5α-andros- tane-3β,17β-diol (3β-Adiol) where it exerts antiproliferative activity. The proliferative action of the androgen receptor is activated by 5α- dihydrotestosterone (DHT). Thus, prostate growth is governed by the balance between androgen receptor and ERβ activation. 3β- Adiol is a high-affinity ligand and agonist of ERβ and is derived from DHT by 3-keto reductase/3β-hydroxysteroid dehydrogenase en- zymes. Here, we demonstrate that, when it is expressed in living cells containing an estrogen response element-luciferase reporter, 17β-hydroxysteroid dehydrogenase type 6 (17βHSD6) converts the androgen DHT to the estrogen 3β-Adiol, and this leads to activation of the ERβ reporter. This conversion of DHT occurs at concentrations that are in the physiological range of this hormone in the prostate. Immunohistochemical analysis revealed that 17βHSD6 is expressed in ERβ-positive epithelial cells of the human prostate and that, in prostate cancers of Gleason grade higher than 3, both ERβ and 17βHSD6 are undetectable. Both proteins were present in benign prostatic hyperplasia samples. These observations reveal that for- mation of 3β-Adiol via 17βHSD6 from DHT is an important growth regulatory pathway that is lost in prostate cancer.

http://www.ncbi.nlm.nih.gov/pmc/articles...117772.pdf