[SweetO]

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/...ogin=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 

Oh boy! Dim!!!   it helps too with hormonal acne! Do you know any good brand, L?