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I would love to be linked to your thread on MSM and HIIT! I’m still struggling to navigate this site in my mobile browser  should I be cycling the DIM?

Sure, I'm posting here ro make it easier for you.

Hi Ladies, I shared the DIM information the other day in my program thread @ Project X, I'm attaching the information here for reference too. I'm also attaching DIM research for PCOS. DlM improves estrogen metabolism, DIM shifts production of the dangerous estrogen metabolite 16a-hydroxy in favor of the beneficial (or healthier) 2-hydroxy 2-OH metabolite. So it's hypothesized that the 2 OH pathway over 16α-OH pathway (which is inversely associated with breast cancer risk) is a safer option.


The promising effect of linagliptin and/or indole-3-carbinol on experimentally-induced polycystic ovarian syndrome
Ahmed M Kabel et al. Chem Biol Interact. 2017.
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Abstract
Polycystic ovarian syndrome (PCOS) is one of the most common medical conditions that lead to female infertility worldwide. The aim of this study was to assess the effect of linagliptin and/or indole-3-carbinol (I3C) on PCOS in female rats. Fifty female Wistar rats were randomly allocated into five equal groups: Control group; Letrozole-induced PCOS group; Letrozole + Linagliptin group; Letrozole + I3C group and Letrozole + Linagliptin + I3C group. Body weight, body mass index, Lee index and ovarian indices were determined. Plasma levels of luteinizing hormone (LH), free testosterone, estradiol, progesterone, prolactin, fasting blood glucose (FBG) and fasting plasma insulin were measured. Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated. Tissue antioxidant status, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and Nrf2/HO-1 content were assessed. Histopathological and immunohistochemical examination of the ovaries were done. Linagliptin and/or I3C induced significant decrease in tissue TGF-β1, TNF-α, IL-10, plasma free testosterone, luteinizing hormone, progesterone, estradiol, FBG and insulin levels associated with significant improvement of insulin resistance whereas tissue Nrf2/HO-1 content and antioxidant enzymes were significantly increased compared to PCOS group. In addition, final body weight, final body mass and Lee indices were significantly decreased compared to PCOS group. Also, there was significant improvement of the ovarian morphology compared to PCOS group. This improvement was significant with linagliptin/I3C combination compared to the use of each of these drugs alone. In conclusion, linagliptin/I3C combination might represent a beneficial therapeutic modality for amelioration of PCOS.

DIM is Diindolylmethane. It is an anticarcinogen and also improves estrogen metabolism. Plant-derived 3,3′-Diindolylmethane Is a Strong Androgen Antagonist in Human Prostate Cancer Cells* DIM is remarkably similar in conformational geometry and surface charge distribution to an established synthetic AR antagonist, although the atomic compositions of the two substances are quite different. Taken together with our published reports of the estrogen agonist activities of DIM, the present results establish DIM as a unique bifunctional hormone disruptor. To our knowledge, DIM is the first example of a pure androgen receptor antagonist from plants.

http://www.jbc.org/content/278/23/21136.full

From the study above on DIM I pulled certain paragraphs of information to highlight. Two main points: DIM inhibits DHT, and DIM is similar to Casodex, which is similar to ??? drum roll please: the prescription anti-androgen Bicalutamide. 

The effects of DIM on human prostate cancer cell growth were examined using LNCaP and PC-3 cells. After a 96-h treatment, DIM produced a concentration-dependent inhibition of LNCaP cell proliferation with maximal inhibition of 70% at 50 μm.

DIM strongly inhibited DHT induction of androgen-responsive genes by more than 50% at 1 μm and more than 90% at 10 μm in both promoter constructs 

Cyproterone acetate and Casodex, two well known antiandrogens, were used as positive controls. DIM and Casodex exhibited similar binding affinity for the AR.

Because both DIM and Casodex act as pure antiandrogens, we compared the structures of these ligands more closely.
the two ligands are remarkably similar in conformation despite their considerable difference in atomic compositions

DIM is remarkably similar in molecular geometry and surface charge distribution to the well established synthetic antiandrogen, Casodex. Our investigation, leads to the conclusion that DIM is a strong, pure androgen antagonist.

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The following is my analysis, or model of how DIM being a pro-aromatase, and it works following the CREB-binding protein

"Cyclic AMP response element binding protein (CREB) activates transcription of cAMP response element (CRE)-containing promoters following an elevation of intracellular cAMP"...which is basically a second messenger and if you've read this thread no doubt you've seen it posted many times lol, it's a pro-breast pathway once inside the cytoplasm. 

How it relates to DIM is the hormone receptors are transferred to common compartments located in the euchromatin region and form a complex with co-activators…I see a window, or an opening. And judging how the rat study below shows how the CYP1B1 cytochrome opens the door for enhanced E2 production I'm feeling more confident the window opening got a little bigger. 

The formation of these nuclear foci is thought to provide platforms for the interaction of nuclear receptor and co-activators (38). Liganded steroid hormone receptors are transferred to common compartments located in the euchromatin region and form a complex with co-activators, such as steroid receptor coactivator 1, transcriptional intermediary factor 2, and CREB-binding protein, which are also accumulated in the same subnuclear compartments. For the AR, CREB-binding protein was found to be essential for foci formation, and the process of compartmentalization is essential for full transactivation 
https://www.jbc.org/article/S0021-9258(20)73423-X/fulltext

Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N -ethyl- N ′-nitro- N -nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism 
https://academic.oup.com/carcin/article/25/11/2257/2475841?login=false

In the assays of estradiol hydroxylase activities in the liver, dietary I3C increased both 2- and 4-hydroxylase activities, in particular the latter. These results strongly suggest that the induction of the CYP 1 family by I3C is linked to modulation of E2 metabolism. 

Meaning DIM can enhance E2 production 

I have more information on HIIT/MSN, but this is a good place to start. 

Good conversation going here, (nice link Ella). MSM does many things, top of the list is breast cancer protection. Indirectly to NBE, MSM upregulates growth hormone, which is essential for breast growth as we know. If we take a lead from this first study we see possible link towards NBE, but, it leans towards favoring males in the liver. I'll look further though.

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.
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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.
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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