[Lotus]

Rapid behavioural effects of oestrogens and fast regulation of their local synthesis by brain aromatase.
Cornil CA1, Charlier TD.
Author information
Abstract
Besides their genomic effects, oestrogens, 17beta-oestradiol in particular, also activate cellular effects that may be too rapid (seconds to minutes) to result from de novo protein synthesis. Although the existence of such nongenomic actions has been extensively demonstrated in vitro, the understanding of their behavioural significance is only emerging. Recent findings provide evidence that acute oestrogen treatments significantly affect a variety of behavioural processes, including sexual behaviour, social communication and cognition. One question arising from these results concerns the source of the oestrogens mediating nongenomic effects in vivo. In this review, data collected in vitro and in vivo are presented supporting the notion that fast modulations of local testosterone aromatisation can rapidly control the local oestrogen concentration in a time frame compatible with their rapid actions. Taken together, these data provide compelling evidence of how rapid changes in the local production and action of oestrogens can shape complex behaviours.

[Lotus]

From the study:

Mechanisms of oestrogen elimination

The behavioural inhibition resulting from the pharmacological blockade of aromatase suggests that there must exist some mechanism(s) able to rapidly clear locally-produced oestrogens to terminate their effects. The elimination of plasma oestrogen is ensured through excretion following their conversion into inactive (or less active) water-soluble metabolites by oxidative metabolism and conjugation (89).


This metabolism mainly occurs in the liver but detectable levels of catabolic activity are also observed in the brain (90–92). Interestingly, in addition to its oestrogen synthase activity, purified aromatase from human placental microsomes also catalyses oestrogen 2-hydroxylation.

It is thus possible that the same enzymatic protein is involved in both the production and the conversion of oestrogens (for further information, see (64)). Finally, passive dilution could also contribute to the rapid equilibration of the high locally synthesized oestrogen concentrations with the much lower brain concentrations.

At such concentrations, brain-derived oestrogens would then no longer be able to sustain membrane effects resulting in their termination. The half-life of oestradiol in the brain is not known, but calculations derived from pharmacokinetic data estimated that its half-life in the blood ranges from 5 to 15 min (63). Therefore, it is conceivable that oestrogen dilution combined with its enzymatic degradation could interrupt oestrogen- dependent signalling in the brain within minutes.

[Lotus]

Also.....glucocorticoids rapidially induce nuclear localization of the glucocorticoid receptor, (when 17beta estradiol is introduced together with glucocorticoids localization occurs in minutes) as did cAMP (second messengers) and E2 synthesis occurs in 15 minutes.

So...what are glucocorticoids types?, prednisone, dexamethasone, and hydrocortisone etc. long term use is dangerous, I'm not suggesting this. My thought is that an anti-inflammatory action inside receptors can speed up its signal to synthesize. To this extent, I'm on the look-out for something to complete this cascade.


Anti-inflammatory actions of glucocorticoids: molecular mechanisms.
http://www.ncbi.nlm.nih.gov/pubmed/9854452

[The First Aria]

thanks so much Pom and Ella, I appreciate the kind words. It's kinda freaky having cleavage (lol, not complaining though).

Hey, you really need to back off some of your non pharma... Your turning into a caricature of yourself.

And just think.... Mounds o' Glory, and still puffy too... OMG! ! hehehehe

[Billie]

I had long hair for 10 years and cut it to fit in a corporate environment but I want to grow it back. I sound pretty fem on the phone and feel more fem and I don't want to feel strange like now. I want to feel like myself. So neutral is a great concept.

Thanks,

When I had long hair I despised the up-keep lol, . However, my reason for cutting it was for me mum to see it short again in her final passing moments of her life..... It brought a smile to her face, then, she was gone a few hours later, I don't regret it one bit.

Wow. That is tough. My parents never commented poorly however I had my hair.

[Lotus]

thanks so much Pom and Ella, I appreciate the kind words. It's kinda freaky having cleavage (lol, not complaining though).

Hey, you really need to back off some of your non pharma... Your turning into a caricature of yourself.

And just think.... Mounds o' Glory, and still puffy too... OMG! ! hehehehe

Um ok, really? haha......

____________________

Wow. That is tough. My parents never commented poorly however I had my hair.

Thanks billyboy, I appreciate the feedback.

[Ms.Ladytobe]

Lotus, after 300 and sum pages i can truly say you are a goddess of the breast world i praise you and your journey. Your commitment is far under praised, i solute you and give you the biggest thanks.

[Marcy]

Lotus, do you think adding hops on top of 4 MG  estrofem  is duplication  or is the hops still valuable for the GH value? I had great results with hops before switching  to  synthetic e2.

[Lotus]

Lotus, after 300 and sum pages i can truly say you are a goddess of the breast world i praise you and your journey. Your commitment is far under praised, i solute you and give you the biggest thanks.

Aw thanks Ms.Ladytobe I'm humbled and honored by your kind words, ( thank you for putting a smile on my face ).

If I can be of any help please let me know.

[Lotus]

Multiple study's point out that certain hormones need to be present (at the same time) to induce breast growth. My conclusion (based on research studies and my own personal results) listed below discusses the missing parts of NBE/HRT. (Choose 1 from each, except EGF (epidermal growth factor) is 2 from that group.


GH-growth hormone

-HOPS (8-PIN) stimulates IGF-1,........growth hormone stimulates IGF-1 (insulin growth factor). This action stimulates new growth. Exercise & sleep, whey (denatured), cayenne pepper stimulates IGF-1 and circulation (inhibits androgens in the prostate). Vitamin D stimulates IGF-1

PRL-prolactin

-hops, milk thistle, nipple stimulation


PR-progesterone & progestrone receptor

-red clover and a structurally similar flavonoid, apigenin, bound to PR and induced progestegenic activity and P4 regulated genes in breast epithelial cells and human endometrial stromal cells (HESC). Kaempferol and apigenin demonstrated higher progestegenic potency in the HESC compared to breast epithelial cells

E2-estradiol-

fenugreek, Hops (binds to breast receptor A), authentic PM. adipose tissue (fat) contributes up to 100% of circulating estrogen in postmenopausal women. I see older genetic males somewhere close to postmenopausal women, BMI being a factor.

EGF- epidermal growth factor-

linoleic acid (18:2 omega 6) and prostaglandin E2 or cAMP has synergistic effect on EGF-stimulated growth (stimulates mammary epithelial cells).

My choice is EPO (evening primrose oil- plus krill oil)....though peanut oil and borage oil could work too. I'll do EPO 2x daily, 1 krill oil per day, then peanuts (high in biotin) with EPO later.

Anti-Androgens and aromatase are still needed, but I see these added at specific times. Meaning taking anti-androgens and aromatase together, then followed by E2/phytoestrogens.

(However, EGF stimulates aromatase..........and EPO inhibits DHT and promotes aromatase). In other words, it's mainly that omega 6's and PGE2 targets these actions.

As we know anti-androgens inhibit 5 alpha reductase, then aromatase converts it to estrogens.

____________________________


Personally, I've added some items to my HRT program to address the multiple hormone approach and have seen a 1/2 growth in the past 3 weeks, 2 inches total since May. Granted, my situation is different from others, I'm not saying you'll see similar results, but it's encouraging based on doing this for the past 4 years. The items I've added are supplements.

E2 4mg x2 daily
Spiro 100mg x2 daily

EPO (evening primrose oil) 1000mg x2 daily
Krill oil 500mg x1 daily
Gelatin 1300mg x2 daily
Vitamin C 500 mg 1x daily
Biotin 5000mcg x2 daily
Magnesium 250mg X1 daily
Calcium 600mg x2 daily
Water 8+ cups daily (w/lemon wedge)
Green Tea 3 cups

I've covered enough of the science in past posts which highlights this info, feel free to read. One other thing I've found very helpful is a tube bra.....lol true. I think it helps move (or keep) breast fat moving forward. The ability to reposition it right below the underarms moves that annoying extra spillage you see overflowing from bras. There's one size fits all or larger ones available, the bands do get uncomfortable after awhile, shop around though. The flush of breast fats/blood moving forward also increases areola sensitivity.


Other moving parts to all this obviously still needs addressing, (exercise/sleep are two such examples that need further mention). A quick note though is coordinating exercise via the release of hormones and supplement timing, (imo, exercise within 1 hour) whether that's 20 squats, walking, HIIT (high intensity interval training), breast isometrics is up to you.

Lotus, do you think adding hops on top of 4 MG estrofem is duplication or is the hops still valuable for the GH value? I had great results with hops before switching to synthetic e2.

Hi Marcy,

From the studies I've seen, HOPS is 70 times more potent for ER-b (estrogen receptor beta) over estradiol and 20,000 times less potent at ER-a (estrogen receptor alpha) over estradiol. If I didn't mention already HOPS upregulates progesterone receptor mRNA (signaling). Besides stimulating IGF-1 HOPs enhances thermogenesis in BAT (brown adipose tissue, aka " fat " ), which means counteracting increases body fat......I know right, I'm thinking beer means beer belly imo, didn't make sense, but here's the study.
http://www.ncbi.nlm.nih.gov/m/pubmed/26098641/

FWIW I don't think HOPS will comprise HRT, for me I'd take it at night time for the IGF-1 stimulation and promotion of PR (progesterone receptor).

Hop and red clover extracts, as well as 8-PN upregulated progesterone receptor (PR) mRNA in the Ishikawa cell line. In the MCF-7 cell line, PR mRNA was significantly upregulated by the extracts, biochanin A, genistein, 8-PN, and IX. The two extracts had EC50 values of 1.1 and 1.9 μg/mL, respectively, in the alkaline phosphatase induction assay. Based on these data, hops and red clover could be attractive for development as herbal dietary supplements to alleviate menopause-associated symptoms.

http://www.ncbi.nlm.nih.gov/pmc/articles...s14948.pdf