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NBE-Research


Lotus

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#1
Open Research Topics

(01-04-2015, 09:12 PM) -Clelia- Wrote:
(01-04-2015, 06:30 AM) Lotus Wrote:
(31-03-2015, 10:10 PM) -Clelia- Wrote: "What's also interesting is how upon excertion steroids are water soluble"-->
mmh... why do you want to know that? for transport?

Yes exactly, (for transport), ion channels are the access of cell diffusion correct?, assuming carrier proteins are the vehicles to mitochondria, what keeps the channels open long enough expression?, I see its from 1/100 hundredth to 1/1000 thousands of seconds, could this explain partial binding?.


I think that there is no necessity of a ion channel for the access of steroids in the cell. They should simply cross the membranes by diffusion:

"After secretion by the endocrine glands, the hormones are transported to the target tissues via the blood, where their major fraction is bound to the serum proteins β-globulin and albumin. According to the genomic mechanism, the lipophilic character of the hormones enables them to dissociate spontaneously from the carriers and enter the target cell by transbilayer passive diffusion. Inside the cell, the hormones bind to intracellular receptors that shuttle between the nucleus and the cytoplasm in an inactive state (Lundberg, 1979). Binding to the hormones induces conformational changes and reorganization to active hormone-receptor complexes (Guiochon-Mantel et al., 1996). Subsequently, the complexes migrate to the nucleus, where they bind to hormone-responsive elements on the DNA and regulate synthesis of new proteins that are required for the hormone's action (Chen and Farese, 1999; Beato and Klug, 2000)."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1304487/



Ok, I understand the "conformational changes and reorganization to active hormone-receptor complexes" now, it took a few months tbh, but I got it now. Big Grin

(01-04-2015, 09:40 PM) -Clelia- Wrote:
(01-04-2015, 06:11 AM) Lotus Wrote:
(31-03-2015, 09:41 PM) -Clelia- Wrote: I think that DHT is not converted to the "estrogen-like metabolite" in the breast, at least not in the same amount as it is in the prostate.


a hypothetical about DHT, (but first), for the longest time I thought DHT had no usable purpose in terms of breast growth. Now, we discover it has a back door useable metabolite in the prostrate and Sertoli cells. So....then, is it yet to be discovered that DHT in breast tissue "can" in fact....have the usable ER-beta metabolite??.....that is my hypothetical, I see you think perhaps the same is true.

We've just opened a whole can of worms.......imo it's the gummi type (yum yum). Big Grin


yes it could be... if you can convert the majority of DHT, in breast tissue, it could be a way for NBE. But i think that this method is quite difficoult to obtain... you should enhance the enzyme that give you 3b-diol, but honestly I dont know how this could be possible.


Honestly that's encouraging news, the possibity of DHT actually being anything of therapeutic value in breast tissue (besides research purposes) is well....uhm....cool.

CoolSmile

Lotus

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Posts: 1,621
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#2
hi Clelia,

The main phyto's of choice at BN is Puearari Mirifica. There variance in potency is a big concern since its been stated its most effective yield is at 10 years for the root tubers. And out of that its only 2 months out of the year. Distributors don't share potency/yield/heavy metal tests etc. Its been stated PM is .25% of estradiol, but it's more like .006 in ER-a and double that in ER-b (or there about). Some of our BN members have had some serious side effects. They range from severe headaches to major bleeding in menstration. I'll provide the threads later. From what I've been able to determine PM up-regulates triglycerides (just like E2), increased blood flow, which I believe interupts with sleep, (as some have reported) and an initial libido increase (again, imo increased blood supply). I'd like to explore any and all interactions if possible. Here's one link to start with. Big Grin


Down regulation of gene related sex hormone synthesis pathway in mouse testes by miroestrol and deoxymiroestrol.

Abstract
Miroestrol and deoxymiroestrol are phytoestrogens isolated from tuberous root of Pueraria candollei var. mirifica. Modulatory effects of miroestrol and deoxymiroestrol on enzymes involved in sex-hormone synthesis pathway in male C57BL/6 mice were investigated using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Miroestrol and deoxymiroestrol suppressed the expressions of 3β-HSD, 17β-HSD1, and CYP17 while CYP19 mRNA expression was slightly decreased. In addition, the expression of 17β-HSD2 was induced in correlation with those did by estradiol. These observations supported that miroestrol and deoxymiroestrol could exhibit the same effect as estradiol regarding regulation of testicular gene related sex hormone synthesis pathway.
Copyright © 2011 Elsevier B.V. All rights reserved.
http://www.ncbi.nlm.nih.gov/pubmed/21856387

pom19

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#3
Star 
Wow, thanks Lotus, what an important research. <3 POM

Lotus

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#4

(03-04-2015, 06:07 PM) pom19 Wrote: Wow, thanks Lotus, what an important research. <3 POM


Thanks Pom, we're taking proactive steps at BN towards current research, here's an important link regarding PM. In English Wink it might explain part of a response (growth) issue seen in genetic males. It's that gate-keeper thing (light switch) called HSD (Hydroxysteroid dehydrogenases) it's an enzyme that's positioned in-between cellular steroid hormones pathways, like E1 to E2. But science also defines them as reductase pathways.


Biological Evaluation of Deoxymiroestrol, a Potent Phytoestrogen from Pueraria candollei var. mirifica

Udomsuk L1, Putalun W1, Juengwatanatrakul T2, Jarukamjorn K1*

Introduction: Deoxymiroestrol is a phytoestrogen isolated from tuberous roots of Pueraria candollei var. mirifica (Leguminosae). Since deoxymiroestrol showed strong estrogenic-like activitiy, it is worth to investigate its biological activity on enzymes related drug metabolism, cytochrome P450s (P450), and sex hormone synthesis pathway, as well as its anti-lipid peroxidation in both in vitro in primary mouse hepatocytes and in vivo in mouse liver. Methods: P450 activities were evaluated in both primary mouse hepatocytes and mouse liver. Expression of CYP1A1, CYP1A2, CYP1B1, CYP2B9, AhR, and ARNT mRNAs were quantified by real- time RT-PCR while their activities were assessed by benzyloxyresorufin and methoxyresorufin O-dealkylation, respectively. Enzymes involved in sex-hormone synthesis pathway in male testes were semi-quantified by RT-PCR. Lipid peroxidation was measured in mouse brain. Results: In primary hepatocytes, expression of AhR, ARNT, and CYP1A1 mRNAs was suppressed whereas that of CYP1B1 was induced by deoxymiroestrol, in which the gene expressions were time- and concentration-dependent patterns compared to those of estradiol. In vivo in mice, deoxymiroestrol enlarged female uterus-weight and -volume as comparable to estradiol. As estradiol did, deoxymiroestrol induced expression of CYP2B9 mRNA whereas those of CYP1A2 were suppressed. Assessment of testicular enzymes involved in sex hormone synthesis pathway showed suppression of 3β-HSD, 17β-HSD1, and CYP17 expressions with those of CYP19 mRNA was slightly decreased by deoxymiroestrol. In addition, the expression of 17β-HSD2 was increased resulting in decreasing estradiol synthesis as that noted by estradiol. In addition, deoxymiroestrol possessed anti-lipid peroxidative activity in mouse brain. Conclusion: These observations suggested deoxymiroestrol as a potential alternative medicine for estradiol according to its distinctive abilities on regulation of related hepatic P450 enzymes and sex hormone-synthesis responsive enzymes, with its beneficent anti-oxidative potential.

http://pharm.kku.ac.th/isan-journal/jour...es_249.pdf

Ok, I think we're seeing a problem here with the down regulation of Hydroxysteroid dehydrogenases (HSDs). In paticlaur 3β-HSD, 17β-HSD1, and 17β-HSD1 catalyzes the activation of estrone (E1) to the most potent estrogen estradiol (E2), predominantly considered as an ezyme of estradiol biosynthesis. Which deoxymiroestrol seems to suppress the action, in other words in males it may interrupt the synthesis of E1 (estrone) to E2 (estradiol).

Which this theory or hypothesis lines up with PM an E1 mediator. Which Dr. Gordon commented on here, albeit from E3 to E1:

Quote:Dr Gordon: First, I have to give credit for this information to Dr. Youssef Mirhom, professor emeritus, pharmacognosist and chief scientific officer at Bio-Botanica. Estriol itself is not a hormone secreted by the ovary, but a deactivation product of estrone and estradiol in the human liver by 16-alpha-hydroxylation. Miroestrol is a phytoestrogen (a plant estrogen), and has the same chemical properties, as well as physiological properties as estriol; however, it has a weaker estrogenic effect. And Professor Sayan Sawatsri M.D., gets the credit for the following valuable bit of information—miroestrol has about 3,000 times the estrogenic activity of soy isoflavones. initially said.


Assessment of testicular enzymes involved in sex hormone synthesis pathway showed suppression of 3β-HSD, 17β-HSD1, and CYP17 expressions with those of CYP19 mRNA was slightly decreased by deoxymiroestrol. In addition, the expression of 17β-HSD2 was increased resulting in decreasing estradiol synthesis as that noted by estradiol


17β-HSD type1: 17β-HSD1 catalyzes the activation of estrone (E1) to the most potent estrogen estradiol (E2), predominantly considered as an ezyme of estradiol biosynthesis.

_________________

Hydrohysteroid Dehydrogenases –
Biological Role and Clinical Importance – Review

http://cdn.intechopen.com/pdfs-wm/40961.pdf

Lotus

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#5
Hi Clelia, I'm back on FAS lol. Big Grin



Lipid Catabolism: Fatty Acids & Triacylglycerols


Control of fatty acid oxidation is exerted mainly at the step of fatty acid entry into mitochondria.

Free fatty acids, which in solution have detergent properties, are transported in the blood bound to albumin, a serum protein produced by the liver.
Several proteins have been identified that facilitate transport of long chain fatty acids into cells, including the plasma membrane protein CD36.

Fatty acids are degraded in the mitochondrial matrix via the b-Oxidation Pathway. For most steps of the pathway there are multiple enzymes specific for particular fatty acid chain lengths. Many of the constituent enzymes are soluble proteins located in the mitochondrial matrix. But enzymes specific for very long chain fatty acids are associated with the inner mitochondrial membrane, facing the matrix.

Fatty acyl-CoA formed outside the mitochondria can pass through the outer mitochondrial membrane, which contains large VDAC channels, but cannot penetrate the mitochondrial inner membrane.
http://www.rpi.edu/dept/bcbp/molbiochem/...m#activate

Index of Key-words
http://www.rpi.edu/dept/bcbp/molbiochem/...xlist.html

________________________________


Pyruvate Dehydrogenase & Krebs Cycle

Pathway localization:

Glycolysis enzymes are located in the cytosol of cells. Pyruvate enters the mitochondrion to be metabolized further.

Mitochondrial compartments:

The mitochondrial matrix contains Pyruvate Dehydrogenase and enzymes of Krebs Cycle, plus other pathways such as fatty acid oxidation.


The inner membrane is the major permeability barrier of the mitochondrion. It contains various transport catalysts, including a carrier protein that allows pyruvate to enter the matrix. It is highly convoluted, with infoldings called cristae. Embedded in the inner membrane are constituents of the respiratory chain and ATP Synthase.

http://www.rpi.edu/dept/bcbp/molbiochem/.../krebs.htm

-Clelia-

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#6
Hi Lotus,
thanks for this thread.
Honestly I didn't have much time yet, to stay here and study the papers... i would like to spend an evening focusing on some research. Not this one, not tomorrow, maybe on thursday.
I like fatty acids, why did you post about FA oxidation?
I know that is not very healthy their oxidation, but there are a lot of pathways involved in fat
See you soon, bye Smile

Lotus

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#7
(13-04-2015, 08:35 PM) -Clelia- Wrote: Hi Lotus,
thanks for this thread.
Honestly I didn't have much time yet, to stay here and study the papers... i would like to spend an evening focusing on some research. Not this one, not tomorrow, maybe on thursday.
I like fatty acids, why did you post about FA oxidation?
I know that is not very healthy their oxidation, but there are a lot of pathways involved in fat
See you soon, bye Smile


Hi Clelia,

My point was what (FA) gets left out of the mitochronia membrane rather than what gets in, seems like an awful waste huh?. Rolleyes

Sure no problem, post whenever you can. I like FA's too lol, I'd like to bounce some omega 7 theories or ideas at you, I'll post what I mean later.
Take care Wink

-Clelia-

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#8
ok, i'm looking forward to it Smile

Lotus

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#9
(16-04-2015, 08:18 PM) -Clelia- Wrote: ok, i'm looking forward to it Smile


Ok cool, first, what do you think of this?, I shared this in another section the other day. But basically I want to fully investigate the prostaglandin PGE 1 & 2 pathway, I know inflammation is directly tied to this pathway, part of which omega 7 may have a benefit, according to Dr. Rozien, I'll provide his hypothesis shortly.

Epidermal growth factor (EGF) increases aromatase activity and expression in MCF-7 and adipose stromal cells and induces expression of cyclooxygenase 2 (COX-2) in adipose stromal cells (Richards et al. 2002). In breast tumors, prostaglandin (PG) E2 increases intracellular cAMP levels and stimulates estrogen biosynthesis (Zhao et al. 1996); furthermore, it up-regulates aromatase activity and expression in adipose stromal cells (Richards & Brueggemeier 2003). EGF affects the expression of 3B- hydroxysteroid dehydrogenase (3B-HSD) type II and CYP17 in NCI-H295R cells (Doi et al. 2001). Also in NCI-H295R cells, up-regulation of aromatase expression by PGE2 has been reported (Heneweer et al. 2004). However, the mechanisms of the effects of EGF and PGE2 on aromatase expression in NCI-H295R cells have not been examined in detail at the molecular biological level. Therefore, we conducted detailed studies on the effects.

Doses of GLA greater than 3,000 mg per day should be avoided because, at that point, production of AA-Arachidonic Acid(rather than DGLA) may increase.

believe it, after we gain a therapeutic edge lol over total T we could be producing more E2 in our testes than the typical post-menopausal women, who produce mainly E1 in their peripheral tissues. And if all you took was a minor AA and an aromatase herb you could still maintain the "therapeutic edge" over GID, of course that's just my opinion, but I think we see/hear more and more evidence to support that hypothesis.

I've been testing that DHEA at 25 to 50 mg increases his estrogen level. However, a woman taking this dose, will see her testosterone increase.

Epidermal growth factor (EGF) increases aromatase activity in adipose (fat) and up regulates cox 2 expression, also PGE2 (prostaglandin), which is done by GLA, gamma linolelic acid, like from evening primrose oil, above 3000mg which goes into AA acid, that's when it's dicey. I might say forskolin does up regulate aromatase, but still risky spiking blood pressure,



Prostaglandins can be synthesized in an adrenocortical carcinoma, and they can work in an autocrine or paracrine fashion. In rabbit chondrocyte and human squamous carcinoma cell lines, EGF induced the secretion of PGE2 via up-regulation of the activities of phospholipase A2 (PLA2) and COX-2 (Sato et al. 1997, Huh et al. 2003). This may suggest that PGE2 acts as a secondary factor to EGF in the up-regulation of aromatase expression. Therefore, we checked whether PGE2 was secreted from NCI-H295R cells in response to EGF. In this study, NCI-H295R cells secreted PGE2 in response to EGF (Fig. 13), and PGE2 increased aromatase activity to a greater extent than other prostaglandins (Fig. 6). The inhibition of EGF-induced aromatase expression with PGE2 receptor antagonists confirmed that PGE2 is the secondary factor of aromatase expression with EGF (Fig. 14). PGE1 also increased aromatase activity to a degree similar to that of PGE2, but EGF could not stimu- late NCI-H295R cells to secrete a sufficient concentration of PGE1 (data not shown) to increase aromatase activity. These results suggest that several prostaglandins are secreted in response to EGF, and that these prostaglandins evoke some intracellular signaling pathways. According to the experiments using several protein kinase inhibitors (Fig. 12), the intracellular signaling pathways that include MAP kinase, and calcium-calmodulin kinase are import- ant for up-regulation of aromatase by EGF. In response to EGF, EGF receptors (receptor-type tyrosine kinase) activate the MAP kinase pathway through phosphorylation of Ras protein. It is also well known that EGF receptors increase the intracellular calcium concentration. Therefore, it would be reasonable to conclude that inhibition of MAP kinase kinase and calcium-calmodulin kinase II down- regulate aromatase expression in NCI-H295R cells. Interestingly, a PKA inhibitor (H-89) down-regulated aromatase activity. This result suggests that the cAMP– PKA pathway is involved in the up-regulation of aromatase

This is a big deal, so anything over 3000 mg of arachidonic acid AA goes to PGE2, but this corse (pathway) up regulate cancer cells (or said to be), what can stop that conversion process?.

Lotus

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#10
Appetite. 2013 Jun;65:1-7. doi: 10.1016/j.appet.2013.01.009. Epub 2013 Jan 30.

Oral administration of omega-7 palmitoleic acid induces satiety and the release of appetite-related hormones in male rats.

Yang ZH1, Takeo J, Katayama M.

Abstract
We have analyzed the effect of palmitoleic acid on short-term food intake in male rats. Administration of omega-7 palmitoleic acid by oral gavage significantly decreased food intake compared to palmitic acid, omega-9 oleic acid, or a vehicle control. Palmitoleic acid exhibited a dose-dependent effect in this context and did not cause general malaise. A triglyceride form of palmitoleate also decreased food intake, whereas olive oil, which is rich in oleic acid, did not. Palmitoleic acid accumulated within the small intestine in a dose-dependent fashion and elevated levels of the satiety hormone cholecystokinin (CCK). Both protein and mRNA levels of CCK were affected in this context. The suppression of food intake by palmitoleic acid was attenuated by intravenous injection of devazepide, a selective peripheral CCK receptor antagonist. Palmitoleic acid did not alter the expression of peroxisome proliferator-activated receptor alpha (PPARα) target genes, and a PPARα antagonist did not affect palmitoleic acid-induced satiety. This suggests that the PPARα pathway might not be involved in suppressing food intake in response to palmitoleic acid. We have shown that orally administered palmitoleic acid induced satiety, enhanced the release of satiety hormones in rats.
Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID: 23376733 [PubMed - indexed for MEDLINE]
 
 

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