[Lotus]

hi there, i see that research go on, well done :-) see you soon Lotus

Hiya Clelia, my scientist friend , yes I'm plodding through, . I'll tell yeah, this new paper below just adds to this theory palmitoylation, it apparently doesn't degrade in the nucleus so fast. I wonder how long the process of degradation is, pretty sure that hormone synthesis inside the nucleus is about 30-to 60 minutes. I'm just curious as to how long it lasts?.



"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, I'm gonna give this a shot at defining why essential fatty acids (EFA's) are important for NBE, any car buffs Lol?.

EFA's are like lubricants for car parts (e.g. molecules, steroids, DNA synthesis etc). They help help carry hormones to receptors, in other words, once they arrive at the cell membranes they (EFA's) make them more bioavailable. Soooo.....using these fat solubles supplements keep us squeaky, get it.



Figure 1: Bioactive lipid synthesis, metabolism and signaling pathways.
http://www.nature.com/nchembio/journal/v6/n7/fig_tab/nchembio.394_F1.html

We should find how this enzyme palmitoyl-acyl-transferases works.

I think I found something that could help improve upon palmitoyl-acyl-transferases. It's called "Acetyl-L-carnitine"

Acetyl-L-carnitine or ALCAR, is an acetylated form of L-carnitine. It is naturally produced by the body, although it is often taken as a dietary supplement. Acetylcarnitine is broken down in the blood by plasmaesterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown.[2]
http://en.m.wikipedia.org/wiki/Acetylcarnitine

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.

Palmitoylation regulates 17β-estradiol-induced estrogen receptor-α degradation and transcriptional activity.

Abstract
The estrogen receptor-α (ERα) is a transcription factor that regulates gene expression through the binding to its cognate hormone 17β-estradiol (E2). ERα transcriptional activity is regulated by E2-evoked 26S proteasome-mediated ERα degradation and ERα serine (S) residue 118 phosphorylation. Furthermore, ERα mediates fast cell responses to E2 through the activation of signaling cascades such as the MAPK/ERK and phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog 1 pathways. 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. However, whether membrane-initiated and transcriptional ERα activities integrate in a unique picture or represent parallel pathways still remains to be firmly clarified. Hence, we evaluated here the impact of ERα palmitoylation on E2-induced ERα degradation and S118 phosphorylation. 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.
http://www.ncbi.nlm.nih.gov/pubmed/22446104