[Lotus]

Last post, sorry if didn't get to answer the last couple of questions posed. Good luck to all, fair winds and seas. Beam me up Scotty.

Btw, No. 1 favorite research post is when a scientist calls you a scientist.

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.

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!

"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

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

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

no worries, of course not

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

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)

Anyway, you could be a scientist.

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!

thank you Lotus, I'm ready to go. Happy me!
yep you gave to a scientist a good homework. How come, am I the only one? Where are all the others? There is a lot of people here. Anyway, you could be a scientist. Meanwhile I leave to you something as well, that I think you will appreciate (if you havent already read them).

" The Androgen Receptor in Breast Tissues " www.ncbi.nlm.nih.gov/pmc/articles/PMC3404296/ (2012) " Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland." www.ncbi.nlm.nih.gov/pubmed/21846805 (2011)

bye, see you soon

Wow thanks Clelia,

You've got me motivated now... from those research papers it led me to research posted below, and from that I see DHT is non-aromatizable as we know.....but!!!!......it also create what's known as a second estrogen effect, ER-b mostly though...(pretty cool huh?). I knew it has this back-door effect, and mostly from 3b-doil. and then it would by mostly brain, bone etc end result, but none the less it does have an ER result. Now Sertoli cells on the other hand has a huge aromatase link, by way of spermatozoa.


Estrogen and androgen receptors: Regulators of fuel homeostasis and emerging targets for diabetes and obesity
http://www.ncbi.nlm.nih.gov/pmc/articles...247852.pdf




Metabolic effects of ERα and ERβ activation in females
Activation of ERα in the central nervous system (CNS) suppresses food intake, increases energy expenditure and decreases body weight. In addition, activation of ERα improves peripheral energy and glucose homeostasis in multiple ways by 1) preventing liver steatosis, suppressing hepatic glucose production and improving insulin sensitivity, 2) enhancing skeletal muscle lipid oxidation, GLUT4 expression and insulin sensitivity, 3) enhancing subcutaneous white adipose tissue (WAT) distribution while decreasing overall WAT mass by decreasing WAT free fatty acid (FFA) uptake, lipid synthesis and increasing lipolysis, 4) favoring pancreatic β-cell survival and function by preventing pro-apoptotic injuries and lipotoxicity, and increasing insulin biosynthesis and glucose-stimulated insulin release (GSIS). Activation of ERβ in the central nervous system (CNS) also suppresses food intake and increases energy expenditure and prevents obesity on a high fat diet. In addition, activation of ERβ affects peripheral energy and glucose homeostasis by 1) favoring pancreatic β-cell survival and function by preventing pro-apoptotic injuries and increasing GSIS, 2) preventing obesity and decreasing WAT mass, 3) promoting insulin resistance in absence of ERα activation. ERα and ERβ metabolic actions on peripheral tissues result from direct activations of ERs in these tissues or from a central ER action affecting peripheral tissues via the autonomous system CNS ERs.




I'll post the DHT target tissues illustration , (way cool)
_________________

And on ther hand---from the study you listed:

Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland.
Conclusion-
Our findings indicate that androgen signaling influences development and structure of the adult mammary gland and that homeostasis between estrogen and androgen signaling in mature glands is critical to constrain the proliferative effects of estradiol.
http://www.ncbi.nlm.nih.gov/pubmed/21846805#

This is really intriguing (specifically) this statement.

flutamide treatment from 12-21 wk increased ductal branching (P = 0.004)

Which I gather (flutamide, AR) does have an impact on side branching.

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

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

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

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

Anyway, you could be a scientist.

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

I want to link these posts together, hopefully you'll see the importance of how fatty acids can and does have a huge impact on NBE. And considering how effective FA's are in low concentrations it's particularly appealing.


Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.

Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells.

Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.
http://www.ncbi.nlm.nih.gov/pubmed/1637346

GLA- gamma-Linolenic acid (like EPO evening primrose oil),

gamma-Linolenic acid does not inhibit 17 beta HSD dehydrogenase activity, which one has yet to be identified


Btw, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play an important role in the regulation of steroid hormones, such as estrogens and androgens.

http://www.ncbi.nlm.nih.gov/pubmed/12570693

It was only a matter of time when this info would be found, enjoy.

Inhibition of steroid 5a-reductase by specific aliphatic unsaturated/fattyacid
http://www.ncbi.nlm.nih.gov/pmc/articles...1-0210.pdf

fatty acids could function as endogenous inhibitors of 5a-reductase


The most potent was y-Linolenic acid, GLA-aka EPO-Evening Primrose Oil.

From the first study,

Type 1 & 5 (17beta HSD) are breast growth potentiators