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Breast Growing Guide
#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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