[Lotus]

The MSM link to NBE is there (here), only it hasn't been discussed as much because it's complicated ....MSM has indirect results for male/female, the following information relates to both sexes. Used correctly MSM has the right potential for all users seeking NBE, you only need to learn how to use it. 

Greetings loved ones:

We're getting closer to solving this nut, please follow along with my madness. a couple weeks I gave info on a protein (enzyme) that feminizes the brain and liver, this is some follow up information. As non scientific as I can get it, imo (based on the science) a certain combination of growth hormone, signaling mechanisms (transducers), human gene (sult1e1 & GH-STAT5 regulates genes linked to steroid metabolism, @ E2 & E1 and testosterone) induces feminization.

Oddly , I remembered that MSM enhances GH signaling via the Jak2/STAT5b pathway...........aka Feminization. dosage wise?, probably good to start with the basic amount. I'm also thinking (liking) what inositol does (thanks mayko, eat mo oranges lol).....more on that later. I'll be on the hunt finding more regulators (meds/supplements) that target this process.........


STAT5 and steroid hormone metabolism
Liver is a target organ for steroid hormone metabolism. Several studies have suggested that GH-STAT5 regulates genes linked to steroid metabolism (Fig. 3). One of these genes, HSD3b5, catalyzes the formation of the relatively inactive androstanediol from the active dihydrotestosterone.33 Hsd3b5 gene expression was down-regulated in the liver of STAT5- deleted male mice.22,32,33 

In contrast, another gene involved in testosterone metabolism, testosterone 16α-hydroxylase (Cyp2b9), which hydroxylates testosterone at the 16α position, was up-regulated in STAT5-deleted male mice.22 Cyp7b1 (oxysterol 7α- hydroxylase), responsible for the hydroxylation of dehydroepiandrosterone, androstenediol, androstanetriol, and 25-hydroxycholesterol, was downregulated in Stat5-deleted male mice.22,29 

Genes associated with estrogen metabolism are also regulated by GH-STAT5. Sult1e1 is the major Sult isoform responsible for the inactivation of β-estradiol via sulfation at physiological concentrations.52 Expression of sult1e1 gene was up-regulated in STAT5- deficient male mice.22,36 Changes in Sult1e1 activity may alter E2 levels and E2-regulated processes in tissues and cells, including those of the liver where it is expressed at significant levels. Sult1e1 was also shown to have high affinity (nM range) for diethylstilbestrol and tamoxifen as well as for E2 and estrone.53,54 Testosterone or estradiol 15alpha-hydroxylase Cyp2a4 gene is female-specific, and this gene is up-regulated in Stat5-deleted male mice.22,35,38

Thus hepatic GH-STAT5 signaling regulates, at least in part, genes involved in hepatic testosterone/estrogen and drug metabolism. Changes in the metabolism of steroid hormones may have a role in alterations in liver function or the development of liver disease. Further studies regarding direct or indirect molecular mechanisms that regulate steroid/drug metabolism by GH-STAT5 pathway will enhance our understanding of functional significance of GH-STAT5 pathway on steroid metabolism in the liver. Overall, many studies have established that GH-STAT5 signaling is key in dictating sex differences in the expression of a large number of liver gene products, including many Cyps and other DMEs. 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427656/pdf/nihms314339.pdf

Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.
Lim EJ1, Hong DY, Park JH, Joung YH, Darvin P, Kim SY, Na YM, Hwang TS, Ye SK, Moon ES, Cho BW, Do Park K, Lee HK, Park T, Yang YM.
Author information

Abstract
Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which methylsulfonylmethane (MSM) inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. We confirmed that MSM significantly decreased the relative luciferase activities indicating crosstalk between STAT5b/IGF-1R, STAT5b/HSP90α, and STAT3/VEGF. To confirm these findings in vivo, xenografts were established in Balb/c athymic nude mice with MDA-MB 231 cells and MSM was administered for 30 days. Concurring to our in vitro analysis, these xenografts showed decreased expression of STAT3, STAT5b, IGF-1R and VEGF. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers.

MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs.
Joung YH1, Lim EJ, Darvin P, Chung SC, Jang JW, Do Park K, Lee HK, Kim HS, Park T, Yang YM.
Author information
Abstract
Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities. But, its effects on bone are unknown. Growth hormone (GH) is regulator of bone growth and bone metabolism. GH activates several signaling pathways such as the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) pathway, thereby regulating expression of genes including insulin-like growth factor (IGF)-1. GH exerts effects both directly and via IGF-1, which signals by activating the IGF-1 receptor (IGF-1R). In this study, we investigated the effects of MSM on the GH signaling via the Jak/STAT pathway in osteoblasts and the differentiation of primary bone marrow mesenchymal stem cells (MSCs). MSM was not toxic to osteoblastic cells and MSCs. MSM increased the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. We found that MSM and GH, separately or in combination, activated GH signaling via the Jak2/STAT5b pathway in UMR-106 cells. Using siRNA analysis, we found that STAT5b plays an essential role in GH signaling activation in C3H10T1/2 cells. Osteogenic marker genes (ALP, ON, OCN, BSP, OSX, and Runx2) were activated by MSM, and siRNA-mediated STAT5b knockdown inhibited MSM-induced expression of osteogenic markers. Furthermore, MSM increased ALP activity and the mineralization of MSCs. Taken together, these results indicated that MSM can promote osteogenic differentiation of MSCs through activation of STAT5b.



Growth hormone pulse-activated STAT5 signalling: a unique regulatory mechanism governing sexual dimorphism of liver gene expression.
Waxman DJ1.
Author information
Abstract
Growth hormone (GH) exerts sexually dimorphic effects on liver gene transcription that are regulated by the temporal pattern of pituitary GH release; this release is intermittent in male rats and nearly continuous in females. Comparisons of liver nuclear protein tyrosine phosphorylation in male and female rats have led to the discovery that the liver transcription factor STAT5b is tyrosine phosphorylated in male but not female rats in response to GH pulses. Intermittent plasma GH pulses trigger a rapid and repeated tyrosine phosphorylation and nuclear translocation of liver STAT5b in intact male rats, while the more continuous pattern of GH exposure down-regulates the STAT5b signalling pathway in female rat liver. The central importance of STAT5b for the physiological effects of GH pulses has been verified using a mouse gene knockout model. STAT5b gene disruption leads to a major loss of multiple sexually differentiated responses associated with the sexually dimorphic pattern of pituitary GH secretion. Male-characteristic body growth rates and male-specific liver gene expression are decreased to wild-type female levels in STAT5b-/- males, while female-predominant liver gene products are increased in males to near female levels. STAT5b is thus a liver-expressed, latent cytoplasmic transcription factor that undergoes repeated tyrosine phosphorylation and nuclear translocation in response to intermittent plasma GH stimulation, and is a key intracellular mediator of the stimulatory effects of GH pulses on male-specific liver gene transcription. Other studies indicate, however, that STAT5a and STAT5b are both required for constitutive expression in female, but not male liver, of certain GH-regulated CYP enzymes. GH activation of both STAT5 proteins, which in turn form distinct homodimeric and heterodimeric DNA-binding complexes, is thus an important determinant of the sex-dependent and gene-specific effects that GH has on the liver.

I think it makes sense to take MSM after a high intensity workout, (biotin too, for its abilty to break down carbs). But because MSM induces binding of STAT5 to the IGF-1R and increases IGF-1 and IGF-1R promotes these activities you'd have to give MSM considerable attention for after workout repair. I like the 12-14 hour intermittent fast, followed by High-intensity Interval Training (HIIT) , that's short bursts of intense work followed by less intense activity or rest. 


Growth hormone signaling in human adipose and muscle tissue during "feast and famine"; Amplification of exercise stimulation following fasting compared to glucose administration.

Conclusions: This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the "feast and famine hypothesis"; the adipose tissue signaling responses which hitherto have not been scrutinized may play a particular role in promoting FFA mobilization. 

http://www.eje-online.org/content/early/2015/06/01/EJE-14-1157.short


Fasting and fitness boost human growth hormone

Intermittent fasting for periods ranging from 12-24 hours along with high intensity exercise has a positive effect on boosting human growth hormone (HGH). HGH is a very important protein-based hormone that is produced by the pituitary gland. HGH enhances the cellular repair processes that allow us to age with grace. HGH regulates metabolism to burn fat, build muscle, and slow down the negative effects of stress.

Researchers at the Intermountain Medical Center Heart Institute found that men who had fasted for 24 hours had a 2000% increase in circulating HGH. Women who were tested had a 1300% increase in HGH.

A 2009 study in the British Journal of Sports Medicine showed that lactic acid accumulation helps to trigger HGH. Lactic acid is only produced in response to intense anaerobic training. Aerobic training is not intense enough to produce the kind of lactate triggering of HGH.

Low-intensity, long duration aerobic training is catabolic in nature. This means that it produces lots of free radicals without promoting significant amounts of repair peptides, enzymes and hormones. The net effect is a wearing down of bodily resources.

High-intensity training also produces free radicals but it triggers an abundance of repair peptides, enzymes and hormones to be released. The net effect of this is healthy tissue repair and favorable effects on body composition and anti-aging qualities.

Learn more:  http://www.naturalnews.com/034704_intermittent_fasting_fitness_HGH.html#ixzz3cAB6XEkK

Effects of growth hormone on adipose tissue
http://www.ncbi.nlm.nih.gov/pubmed/11086655

MSM from a clinical standpoint relieves oxidative stress, anti-cancer properties, decreases muscle damage, suppresses breast cancer, anti-inflammatory,  helps relieve osteoarthritis, etc..etc. 

The non-medical version
http://naturalmom.com/MSMart.htm

Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.
http://www.ncbi.nlm.nih.gov/pubmed/22485142

Effect of methylsulfonylmethane supplementation on exercise - Induced muscle damage and total antioxidant capacity.
http://www.ncbi.nlm.nih.gov/pubmed/22525653

Arginine L-alpha-ketoglutarate, methylsulfonylmethane, hydrolyzed type I collagen and bromelain in rotator cuff tear repair: a prospective randomized study.
http://www.ncbi.nlm.nih.gov/pubmed/23043451

Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study.
http://www.ncbi.nlm.nih.gov/pubmed/23013531

Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.
http://www.ncbi.nlm.nih.gov/pubmed/16309928

Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis.
http://www.ncbi.nlm.nih.gov/pubmed/24575169

Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise.
http://www.ncbi.nlm.nih.gov/pubmed/24523764


Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats.
http://www.ncbi.nlm.nih.gov/pubmed/24106592

Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice.
http://www.ncbi.nlm.nih.gov/pubmed/23595869

Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis.
http://www.ncbi.nlm.nih.gov/pubmed/24575169

Combination of AG490, a Jak2 inhibitor, and methylsulfonylmethane synergistically suppresses bladder tumor growth via the Jak2/STAT3 pathway.
http://www.ncbi.nlm.nih.gov/pubmed/24402583

The "MESACA" study: methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis.
http://www.ncbi.nlm.nih.gov/pubmed/21986780

Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men.
http://www.ncbi.nlm.nih.gov/pubmed/21899544


The effect of methylsulfonylmethane on the experimental colitis in the rat.
http://www.ncbi.nlm.nih.gov/pubmed/21463646

Efficacy of glucosamine, chondroitin, and methylsulfonylmethane for spinal degenerative joint disease and degenerative disc disease: a systematic review.
http://www.ncbi.nlm.nih.gov/pubmed/21403782


Effect of topical application of methylsulfonylmethane (MSM), EDTA on pitting edema and oxidative stress in a double blind, placebo-controlled study.
http://www.ncbi.nlm.nih.gov/pubmed/21366964