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B.i.G.G (Breast Information Growing Guide Lv.2)

#41

(20-09-2017, 01:06 AM)Lotus Wrote:  It's Interesting that E2 + spiro + MSM has an effective inhibiting effect over DHT, and thus boosting spiro's ability (or bioavailability).

I want what I take to do more....so taking MSM with spiro does exactly that. In other words, less is more when taking spiro with MSM, which MSM is dimethyl sulfide: the presence of a dimethyl group at the alpha-position of the lactone carbonyl increases the selectivity of the inhibitor toward 17beta-HSD5. Compound 26, a 3-deoxyestradiol derivative with a dimethylated spiro-delta-lactone at position 17, possesses the most potent inhibitory activity for 17beta-HSD5 (IC(50)=2.9 nM).


Clin Endocrinol (Oxf). 1978 Dec;9(6):523-33.
Increased serum oestrone and oestradiol following spironolactone administration in hypertensive men.

Miyatake A, Noma K, Nakao K, Morimoto Y, Yamamura Y.
Abstract
The present study was undertaken to evaluate long-term effects of spironolactone on basal serum oestrone, oestradiol, testosterone, LH and prolactin concentrations in hypertensive male patients. Serum prolactin response to TRH was also evaluated. Patients were divided into two groups: a conventional-dosage group, consisting of six males with essential hypertension who took 75 to 150 mg of spironolactone daily for 12 weeks, and a high-dosage group, consisting of two males with idiopathic hyperaldosteronism who took 300 mg of spironolactone daily for more than 40 weeks. In the conventional-dosage group, serum oestrone concentrations significantly increased (P less than 0.01) at 12 weeks, serum oestradiol concentrations gradually increased throughout the study period, however, the increments were not statistically significant (P less than 0.2). Basal serum testosterone, LH and prolactin concentrations were not significantly changed throughout the study period. Enhancement of serum prolactin response to TRH was not found in any of the patients in the conventional-dosage group. In the high-dosage group, serum oestrone maintained high levels from the beginning of this study, and serum oestradiol concentrations increased with the development of gynaecomastia. Serum testosterone, LH and prolactin concentrations did not show any definite change throughout the study period. Thus, long-term spironolactone treatment increased the serum levels of oestrone and oestradiol in hypertensive men followed by the development of gynaecomastia. The elevation in circulating oestrogens could well explain the oestrogenic side-effects of spironolactone treatment.
PMID: 747893
[Indexed for MEDLINE]



(30-12-2016, 11:45 PM)Lotus Wrote:  Greetings,  Smile


Steroidal lactones as inhibitors of 17beta-hydroxysteroid dehydrogenase type 5: chemical synthesis, enzyme inhibitory activity, and assessment of estrogenic and androgenic activities.
Bydal P1, Luu-The V, Labrie F, Poirier D.
Author information

* 1Medicinal Chemistry Division, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and University Laval, 2705 Laurier Boulevard, Québec, Québec G1V 4G2, Canada.
Abstract
Androgens are well known to play a predominant role in prostate cancer and other androgen-dependent diseases. To decrease the level of androgen testosterone in the prostate, we are interested in developing inhibitors of 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5). This enzyme expressed in the prostate is one of the two enzymes able to convert 4-androstene-3,17-dione into testosterone. From a screening study, it was found that a series of steroid derivatives bearing a lactone on D-ring demonstrated potent inhibition of 17beta-HSD5 over-expressed in HEK-293 cells. The results of enzymatic assays using intact cells indicated that a C18-steroid (estradiol or 3-deoxyestradiol) backbone and a spiro-delta-lactone (six-member ring) are important for a strong inhibitory activity. Moreover, the presence of a dimethyl group at the alpha-position of the lactone carbonyl increases the selectivity of the inhibitor toward 17beta-HSD5. Compound 26, a 3-deoxyestradiol derivative with a dimethylated spiro-delta-lactone at position 17, possesses the most potent inhibitory activity for 17beta-HSD5 (IC(50)=2.9 nM). It showed no binding affinity for estrogen, androgen, progestin and glucocorticoid receptors (ER, AR, PR and GR). A weak proliferative effect was, however, observed on ZR-75-1 (ER+) cells in culture at high concentration (1 microM), but not at 0.03 microM. Interestingly, no significant proliferative effect was detected on Shionogi (AR+) cells in culture in the presence of 0.1 and 1 microM of lactone 26.


So check this out:

C18-steroid (estradiol or 3-deoxyestradiol) backbone and a spiro-delta-lactone (six-member ring) are important for a strong inhibitory activity.

My translation?, estradiol with spiro demonstrated a potent inhibition of 17beta-HSD5 in the prostate ( inhibiting DHT). Now when a dimethyl group (e.g. MSM) was added it had the strongest inhibiting effect.

even more loosely translated  Rolleyes  E2 + spiro + MSM has an effective inhibiting effect over DHT, and thus boosting spiro's ability (or bioavailability).

A couple other interesting spiro studies:


Pathophysiology of spironolactone-induced gynecomastia.
Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH.
Abstract
Peripheral blood levels of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone and the metabolic clearance rates of testosterone and estradiol, as well as the peripheral conversion of testosterone into estradiol, were measured in 16 patients with hypertension. Six of these patients were treated with spironolactone and developed gynecomastia. The other 10 patients served as control subjects. The blood testosterone level in the spironolactone-treated group (2.7 +/- 0.5 ng/ml) was significantly less (P less than 0.02) than in the control group (4.4 +/- 0.4 ng/ml). On the other hand, blood estradiol levels in the spironolactone group (30 +/- 4 pg/ml) were significantly greater (P less than 0.01) than in the control group (13 +/- 2 pg/ml). These changes were primarily due to significant increases in the metabolic clearance rate of testosterone (P less than 0.02) and in the rate of peripheral conversion of testosterone into estradiol (P less than 0.001) in the spironolactone-treated group. Thus, spironolactone does alter the peripheral metabolism of testosterone resulting in changes in the ratio of testosterone to estradiol, which could contribute to the production of gynecomastia.
PMID: 907238

Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism.
Prior JC1, Vigna YM, Watson D.
Author information


Abstract
The clinical and hormonal response to 12-month therapy with the antiandrogen, spironolactone, in conjunction with near-physiologic doses of female gonadal steroids in 50 transsexual males, is presented. An unselected referred series of 61 men with the psychiatric diagnosis of transsexualism was treated; 10 subjects who had received previous gonadal surgery and 1 man with Klinefelter's syndrome were excluded. Twenty-seven conventionally treated (CT; high-dose estrogen), age 34.4 +/- 10.5 years, mean +/- SD, and 23 untreated patients (SPS), age 30.7 +/- 6.2 years, were studied. Following the initial visit, all 50 were begun on spironolactone and low-dose female hormone therapy. Despite high-dose estrogen treatment for more than 2 years, the mean testosterone (T) level for the CT group was not in the female range (169 +/- 193 ng/dl; normal 20-80). Spironolactone, in doses of 200-600 mg/day, lowered T to the female range in both groups after 12 months (CT 87 +/- 111 and SPS 49 +/- 41 ng/dl). This was achieved in the CT group despite decreases in estrogen dose and discontinuation of parenteral therapy. SPS subjects experienced significant decreases in plasma T (642 +/- 236 to 49 +/- 41 ng/dl, p less than 0.001). Systolic blood pressure dropped (128 +/- 14 to 121 +/- 14 mm Hg, p less than 0.05). The clinical response, including decreased male pattern hair, breast development, feminization, and lack of erections was excellent in most subjects.
PMID: 2540730
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#42

(07-09-2017, 03:54 AM)Lotus Wrote:   

growth hormone (GH) stimulates IGF-1, but IGF-1 oddly enough reduces GH.....the pituitary GH signal is immediate, while liver GH is slow to process...and takes longer to exit the liver.

However, E2 and GH are like best buddies, they can stimulate IGF-1, and that's the part that intrigues me the most. I've come to realize that taking breast growth to the next level means duplicating growth spurts (or mini cascades if you will).....mirroring that growth spurt's in puberty  and pregnancy. So...HPG->E2 -> GH -> IGF-1 -> inhibit somatostatin -> EOP (endogenous opioid peptides)....these actions occurs only in pubety.....our goal is to prove that hypothesis wrong, we will find little known pathway(s) and it's appropriate synthesis for our needs....without using steroids....and improving nitrogen loss.

GH / IGF-1 (growth hormones) with estradiol, that combination helps developed TEB's (terminal end buds)....in other words the essential part of mammary ductal system. GH improves estrogen receptors, like taking L-arginine, Glutamine, Glycine and a few others up-regulates GH. And btw, developing TEB (terminal ends buds are likely the first stage of breast growth in puberty), though I believe you can still grow (or mature) TEB's in adulthood.

wish us luck.  Big Grin
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#43

Hi Lotus love,

First of all, what a killer post <3

I’ve got a question, I am sure you can pintpoint me in the right direction Smile

Def not an expert (yet) on extraction, just know some basics.

It’s about White Peony Root (not leaves or anything, just the root).
You wrote that an ethanol extract would be good. But I was looking up the ingredient responsible for the aromatase effect, which is Paeoniflorin. 

Paeoniflorin is water-soluble, so why would an alcohol extract be needed?
Would a bit of glycerine not be much better?




Water soluble talked about in here: (use search option)
Anti-Inflammatory and Immunomodulatory Effects of Paeonia Lactiflora Pall., a Traditional Chinese Herbal Medicine

The original Paper about anti-androgenic effect. Keep a sheet of your hormone conversion next to you when you read it (wikipedia has a great one atm), it looks like the licorice components are more potent at first glance, but essentially WPR has higher aromatase effect:
Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production.
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#44

Thanks MissMad. The following post is also shared here:
https://www.breastnexum.com/showthread.p...6&page=416


(25-02-2020, 08:24 AM)Lotus Wrote:  Greetings,

I wanted to introduce (and explain) the first of it's kind model for increasing breast growth using cell energy. Cell's (in the human body) have a lipid bilayer which can either let certain (messages/signals) molecules and ions pass through its receptor sites (on the outside of the cell membrane) or block them.

Fat burning hormones want in...to the nucleus that is. But....when cellular inflammation is occuring outside of this lipid bilayer the signals (messages) won't be able to pass.

What this means is those fat burning hormones unable to synthesize in this scenario is highly inefficient....meaning lost potential for cells to complete its goal of synthesizing DNA into new tissue growth...so to speak.

What causes inflammation of cells?, a number of things quite honestly (e.g. stress, diabetes, poor sleep, poor diet, environmental toxins, cancers, thyroid issues, leaky gut, etc etc...you get the picture)

Get to the point Lotus..? okay okay lol, those (that) fat burning hormones I spoke of are is Leptin. And let's say Leptin makes it way in to the mitochondria (barring mitochondrial dysfunction...which is topic for another discussion) Leptin stimulate aromatase, I'll repeat...stimulating Leptin releases the enzyme aromatase...and as we know aromatase stimulates the conversion of androgens into estrogen.

Leptin explained, a Hormone That Regulates Body Weight. Leptin is a hormone that is produced by your body's fat cells ( 3 ). It is often referred to as the "satiety hormone" or the "starvation hormone." Leptin's primary target is in the brain — particularly ...
https://www.healthline.com/nutrition/leptin-101

Leptin directly stimulates aromatase activity in human luteinized granulosa cells.
https://www.ncbi.nlm.nih.gov/m/pubmed/10421796/

So how do we get this done?, by using exogenous ketones. Exogenous ketones double the electron transport chain and uncoupling protiens thereby improving the mitochondrial proteins in brown fat....think thermogenesis and stimulation of ATP. ATP adenosine triphosphate, is known as cellular currency....ENERGY, and all cells use ATP. I use a HMB (short for β-Hydroxy β-methylbutyric acid) which the one use is a free form-beta-acid-hydroxy-methylbutyrate for my exogenous ketone, it induces protein synthesis through the mTOR pathway and appears to be more active than the using calcium bound butyrate brand.


What Are Exogenous Ketone Supplements?
https://www.healthline.com/nutrition/exo...upplements

Excitatory amino acids activate the enzyme aromatase. Now, estrogen can trigger excitatory neurotransmitters like glutamate, which it appears it will calm the dopamine response. And perhaps one benefit of that calming would reduce food craving. This would help let the Ketones do their thing imo, I think taking 1000 to 1500 mg of glutamine could work though.

Not getting  too far  ahead here, but the branching of breast tissue (aka TEBs- terminal end buds) is a combination of integrins, amphiregulin, metalloproteinase and epidermal growth factor receptors (EGFR). The pituitary stimulates IGF-1 (insulin growth favtor) which then stimulates TEB formation and mammary epithelial branching, but you'll need estrogen for this magic to work. And this activation is using the PrlR/Jak2 pathway by utilizing prolactin leads to the induction of other signaling pathways, such as the mitogen-activated protein kinase (MAPK) and PI 3-kinase (PI3K) pathways. And whoever said prolactin has nothing to do with breast growth is (sorry to say) just plain nuts lol.

Sheesh...look at the time, gotta run. But let the revolution begin. Rolleyes
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#45

Lotus! So good to see you back!

I was wondering if you knew a posible combination with Reishi that could help me with converting T into E?

I've got a blood pannel finding out I am in the limit in every type of T being a women Rolleyes  meaning I have high T, Free T, and DHAs lol. My Endo suspects it is PCOS but I do ovulate every single month and I do not have insulin resistance so idk how on earth could be PCOS just suffering hirsutism, but anyways xD

I am finding a way to reduce DHT and free T, so I am currently taking Red Reishi liquid extract and spearmint as well (will upgrade both slowly) but I read somewhere I do need an aromatase enzyme to make the conversion sooo Big Grin  any ideas??
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#46

(25-02-2020, 11:17 AM)sweetorange Wrote:  Lotus! So good to see you back!

I was wondering if you knew a posible combination with Reishi that could help me with converting T into E?

I've got a blood pannel finding out I am in the limit in every type of T being a women Rolleyes  meaning I have high T, Free T, and DHAs lol. My Endo suspects it is PCOS but I do ovulate every single month and I do not have insulin resistance so idk how on earth could be PCOS just suffering hirsutism, but anyways xD

I am finding a way to reduce DHT and free T, so I am currently taking Red Reishi liquid extract and spearmint as well (will upgrade both slowly) but I read somewhere I do need an aromatase enzyme to make the conversion sooo Big Grin  any ideas??

Hi sweetorange,

That's puzzling, PCOS is insulin driven, do share the test results when you can. As I laid out in the previous post I do believe Leptin to be the best course for stimulating aromatase. Not to be redundant, but check out this post from the genetic male forum:


(25-02-2020, 01:11 PM)Happyme Wrote:   Thanks Lotus!
 Its been a long time since I've read your scientific works, but I surprised my self and actually understood it... well kinda
 Welcome back, I hope you are doing well and all your dreams are coming true.
 Looking forward to part two.
 love ya
 Bobbi
 

Hi Bobbi,

thanks, I'm doing good, I hope you are doing the same, have you added new muscle to the auto collection?. I'm glad the info makes some sense. I think it's high time we find something that works for NBE for the least amount of cash, don't you?, and what better way to do that than looking inward...under the hood so to speak (meaning the human body).

So basically insulin is a hormone that stores fat...while Leptin burns fat. And by using these two hormones to make aromatase seems quite simple...eh?, well that's the plan anyways.

Part of that trick is to use up ATP...adenosine triphosphate (aka that cellular energy discussed in the previous post), meaning when a cell uses up all its energy it flips to using ketones for energy rather than glucose.

Biochemistry, Ketogenesis
https://www.ncbi.nlm.nih.gov/books/NBK493179/

So once the body burns up all stored fat as energy then the magic begins to utilize leptin, and this happens not just in fat cells but in the brain too, yup, the brain uses leptin stored in ye old noggin. Which also means the brain releases aromatase.

But the physiological mechanisms of how the brain populates leptin-sensitive neurons is truly astonishing. I won't go down that rabbit just yet, trust me when I say that leptin stimulates the hypothalamus through the Jak-Stat signaling pathway, which i've clearly shown the linkage of this pathway for breast growth in dozens of posts.

Leptin signaling in brain: A link between nutrition and cognition?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670357/

So I'll close with this for tonight, if i told you one can take a PM supplement or E2 tablet (or injection) with an anti-androgen (reishi or finasteride...or you choose) with an exogenous-ketone supplement, and with MSM (because it stimulates the Stat5 pathway) and possibly taking L-carnitine (Acetyl-CoA [acetyl coenzyme A] is a precursor to beta hydroxy butyrate and stimulates ATP) would you believe me it will stimulate breast growth?

Lol...stayed tuned then.

Acetyl-CoA
https://en.m.wikipedia.org/wiki/Acetyl-CoA
Reply
#47

(28-02-2020, 05:55 AM)Lotus Wrote:  
(25-02-2020, 11:17 AM)sweetorange Wrote:  Lotus! So good to see you back!

I was wondering if you knew a posible combination with Reishi that could help me with converting T into E?

I've got a blood pannel finding out I am in the limit in every type of T being a women Rolleyes  meaning I have high T, Free T, and DHAs lol. My Endo suspects it is PCOS but I do ovulate every single month and I do not have insulin resistance so idk how on earth could be PCOS just suffering hirsutism, but anyways xD

I am finding a way to reduce DHT and free T, so I am currently taking Red Reishi liquid extract and spearmint as well (will upgrade both slowly) but I read somewhere I do need an aromatase enzyme to make the conversion sooo Big Grin  any ideas??

Hi sweetorange,

That's puzzling, PCOS is insulin driven, do share the test results when you can. As I laid out in the previous post I do believe Leptin to be the best course for stimulating aromatase. Not to be redundant, but check out this post from the genetic male forum:


(25-02-2020, 01:11 PM)Happyme Wrote:   Thanks Lotus!
 Its been a long time since I've read your scientific works, but I surprised my self and actually understood it... well kinda
 Welcome back, I hope you are doing well and all your dreams are coming true.
 Looking forward to part two.
 love ya
 Bobbi
 

Hi Bobbi,

thanks, I'm doing good, I hope you are doing the same, have you added new muscle to the auto collection?. I'm glad the info makes some sense. I think it's high time we find something that works for NBE for the least amount of cash, don't you?, and what better way to do that than looking inward...under the hood so to speak (meaning the human body).

So basically insulin is a hormone that stores fat...while Leptin burns fat. And by using these two hormones to make aromatase seems quite simple...eh?, well that's the plan anyways.

Part of that trick is to use up ATP...adenosine triphosphate (aka that cellular energy discussed in the previous post), meaning when a cell uses up all its energy it flips to using ketones for energy rather than glucose.

Biochemistry, Ketogenesis
https://www.ncbi.nlm.nih.gov/books/NBK493179/

So once the body burns up all stored fat as energy then the magic begins to utilize leptin, and this happens not just in fat cells but in the brain too, yup, the brain uses leptin stored in ye old noggin. Which also means the brain releases aromatase.

But the physiological mechanisms of how the brain populates leptin-sensitive neurons is truly astonishing. I won't go down that rabbit just yet, trust me when I say that leptin stimulates the hypothalamus through the Jak-Stat signaling pathway, which i've clearly shown the linkage of this pathway for breast growth in dozens of posts.

Leptin signaling in brain: A link between nutrition and cognition?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670357/

So I'll close with this for tonight, if i told you one can take a PM supplement or E2 tablet (or injection) with an anti-androgen (reishi or finasteride...or you choose) with an exogenous-ketone supplement, and with MSM (because it stimulates the Stat5 pathway) and possibly taking L-carnitine (Acetyl-CoA [acetyl coenzyme A] is a precursor to beta hydroxy butyrate and stimulates ATP) would you believe me it will stimulate breast growth?

Lol...stayed tuned then.

Acetyl-CoA
https://en.m.wikipedia.org/wiki/Acetyl-CoA

I made a thread if anyone was interested in helping me to figure things out! ^^

https://www.breastnexus.com/showthread.p...#pid207091

These are just for my hormones part but I have a complete panel if you would like to see it.

Now I'll read Bobbi's thread as well ^^

Thank you so much!
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#48

I believe anything you say. Tongue Your growth already prooved it lol. I am going for this hmb supplement asap. Want to combine it with amino acids and perhaps my new future birth control depo provera.

This really sounds great L. Finally something new, youre so good at this Wink
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#49

(03-03-2020, 09:25 AM)hannah Wrote:  I believe anything you say. Tongue Your growth already prooved it lol. I am going for this hmb supplement asap. Want to combine it with amino acids and perhaps my new future birth control depo provera.

This really sounds great L. Finally something new, youre so good at this Wink

Hannnn <3 I am going to start with hmb this week too! ^^
Reply
#50

(03-03-2020, 12:44 PM)sweetorange Wrote:  
(03-03-2020, 09:25 AM)hannah Wrote:  I believe anything you say. Tongue Your growth already prooved it lol. I am going for this hmb supplement asap. Want to combine it with amino acids and perhaps my new future birth control depo provera.

This really sounds great L. Finally something new, youre so good at this Wink

Hannnn <3 I am going to start with hmb this week too! ^^

Oh cool!! Hope you'll do good on it. Are you going to add more to your regime? 
I heard it is good for muscles too..you are interested in healthy muscles as well right?(lol, sounds weird) my muscles are very weak especially at the start of my legs due too the big head of my son I gave birth too, like years ago.  Shy Blush but I never really fully recovered after giving birth.. maybe this gives me some extra power..who knows..

Xoxo
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