[Lotus]

i've been reading different things on this website, and i'd appreciate one more from this thread please =]]

is Green Tea (preferably green tea capsules - 500mg) an anti-androgen? or does it block DHT???

thanks in advance xoxoxo

Sorry 45 for the DHT frustration, green tea is not so cut and dry in terms of an effective DHT blocker, it depends on what research you find, meaning it's pretty confusing. If you want the short answer (which I assume is yes), I'd choose something else (e.g. reishi). According to this report its effective as a 5 ar inhibitor (blocks the conversion path to DHT). Human studies are lacking though.


Department of Biochemistry and Molecular Biology, The Ben May Institute for Cancer Research, and The Tang Center for Herbal Medicine Research MC6027, University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA.

The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.

[Lotus]

Sorry people, I have to share this rather unique way to box out DHT, I stumbled across it when I was collecting some research, please follow along (my apologies for the technical crap explanation) I'll try to keep it in the ball park.

The problem with DHT is when it enters into receptors it locks it up, and thereby making Aromatase an after thought, Aromatase is enzyme that converts free T to estrogen. (Aka boob growth), here I suggest a novel (well, at least for BN) called "Androgen Decoy's".


http://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=3132148_nihms255516f1.jpg



   

A transcriptional factor decoy strategy is the use of short double-stranded oligodeoxynucleotides containing a high-affinity binding site for specific transcription factors as a decoy DNA to be transfected into target cells [12–16]. Inside the cells, the decoy DNA competes with the endogenous high-affinity binding site of the target genes for binding to specific transcription factors, and consequently inhibits activated AR function [16]. Decoy DNA has potential for treatment of cardiovascular disease [12]. It also induces apoptosis in certain cell lines [13].

Androgen receptor decoy molecules block the growth of prostate cancer
http://www.pnas.org/content/104/4/1331.abstract


Androgen receptor: structure, role in prostate cancer and drug discovery
Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herei
http://www.nature.com/aps/journal/vaop/n....html#fig1

[Lotus]

Sorry people, I have to share this rather unique way to box out DHT, I stumbled across it when I was collecting some research, please follow along (my apologies for the technical crap explanation) I'll try to keep it in the ball park.

The problem with DHT is when it enters into receptors it locks it up, and thereby making Aromatase an after thought, Aromatase is enzyme that converts free T to estrogen. (Aka boob growth), here I suggest a novel (well, at least for BN) called "Androgen Decoy's".


http://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=3132148_nihms255516f1.jpg





A transcriptional factor decoy strategy is the use of short double-stranded oligodeoxynucleotides containing a high-affinity binding site for specific transcription factors as a decoy DNA to be transfected into target cells [12–16]. Inside the cells, the decoy DNA competes with the endogenous high-affinity binding site of the target genes for binding to specific transcription factors, and consequently inhibits activated AR function [16]. Decoy DNA has potential for treatment of cardiovascular disease [12]. It also induces apoptosis in certain cell lines [13].

Androgen receptor decoy molecules block the growth of prostate cancer
http://www.pnas.org/content/104/4/1331.abstract


Androgen receptor: structure, role in prostate cancer and drug discovery
Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herei
http://www.nature.com/aps/journal/vaop/n....html#fig1

The mechanism of action of testosterone.
Testosterone enters the cell by passive diffusion and is converted to DHT and estradiol. Testosterone and DHT bind to the androgen receptor located in the cytoplasm attached to heat-shock proteins (not shown). Upon binding of testosterone and DHT to androgen receptor, heat-shock protein is released and the receptor dimerizes. Estradiol binds to the estrogen receptors ERα, ERβ

Androgen and AR action. Genome organization of the human androgen receptor gene and the functional domain structure of the androgen receptor protein. (A) Androgen and AR signaling in prostate cells. After testicular synthesis, testosterone is transported to target tissues such as the prostate and becomes converted to dihydrotestosterone (DHT) by 5-α-reductase. DHT binds to the ligand-binding pocket and promotes the dissociation of heat-shock proteins (HSPs) from the AR. The AR then translocates into the nucleus, dimerizes and binds to the androgen response element (ARE) in the promoter region of target genes such as prostate-specific antigen (PSA) and TMPRSS2. At the promoter, the AR is able to recruit members of the basal transcription machinery [such as TATA-box-binding protein (TBP) and transcription factor IIF (TFIIF)] in addition to other coregulators such as members of the p160 family of coactivators and cAMP-response element-binding protein (CREB)-binding protein (CBP). SHBG: serum sex hormone-binding globulin. (B) The androgen receptor gene has been mapped to the long arm of the X-chromosome (locus: Xq11-q12). It contains eight exons interrupted by introns of varying lengths (0.7–2.6 kb) and codes for a protein of 919 amino acids consisting of several functional domains (N-terminal domain (NTD), DNA binding domain (DBD) and ligand binding domain (LBD); amino acid residue numbers are indicated above the AR protein domain map). Exon 1 codes for the NTD, exons 2 and 3 encode the DBD, and exons 4 to 8 encode both the hinge and LBD.


   



Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity.

Abstract
Androgens exert their effects by binding to the highly specific androgen receptor (AR). In addition to natural potent androgens, AR binds a variety of synthetic agonist or antagonist molecules with different affinities. To identify molecular determinants responsible for this selectivity, we have determined the crystal structure of the human androgen receptor ligand-binding domain (hARLBD) in complex with two natural androgens, testosterone (Testo) and dihydrotestosterone (DHT), and with an androgenic steroid used in sport doping, tetrahydrogestrinone (THG), at 1.64, 1.90, and 1.75 A resolution, respectively. Comparison of these structures first highlights the flexibility of several residues buried in the ligand-binding pocket that can accommodate a variety of ligand structures. As expected, the ligand structure itself (dimension, presence, and position of unsaturated bonds that influence the geometry of the steroidal nucleus or the electronic properties of the neighboring atoms, etc.) determines the number of interactions it can make with the hARLBD. Indeed, THG--which possesses the highest affinity--establishes more van der Waals contacts with the receptor than the other steroids, whereas the geometry of the atoms forming electrostatic interactions at both extremities of the steroid nucleus seems mainly responsible for the higher affinity measured experimentally for DHT over Testo. Moreover, estimation of the ligand-receptor interaction energy through modeling confirms that even minor modifications in ligand structure have a great impact on the strength of these interactions. Our crystallographic data combined with those obtained by modeling will be helpful in the design of novel molecules with stronger affinity for the AR.

http://www.ncbi.nlm.nih.gov/pubmed/16641486?dopt=Abstract&holding=npg

[Lotus]

The use of Prolactin towards DHT,
Prolactin augmentation of DHT effects is envisioned as resulting from interaction of prolactin with its receptor, which is due to the large size of prolactin molecules.

When testosterone enters the cell cytoplasm it is subsequently converted to the more "active" androgen, dihydrotestosterone, DHT, by reduction at the 5alpha position, this is normal. Dihydrotestosterone is then either bound to a cytoplasmic "receptor" protein Rc, or is further metabolized to either 5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol ,DIOL. The binding of DHT to its cytoplasmic receptor protein results in translocation of the steroid-receptor complex into the nucleus where presumably the complex dissociates and DHT exerts its androgenic effects.

The transport of DHT to the nucleus can also result from the conversion of testosterone to DHT by nuclear membrane-bound 5alpha-reductase. Prolactin augmentation of DHT effects is envisioned as resulting from interaction of prolactin with its receptor, which due to the large size of the prolactin molecule is probably located in or on the plasma membrane.

Large amounts of androgens look for a transporter so that it can bind to the androgen receptors, so it uses prolactin which has a high affinity to cytoplasmic receptor protein, allowing the androgens, testosterone, to be carried and allowing them to convert to dht, only problem is prolactin hormone or luteotropic hormone is synthesised and secreted by sex binding lactotrope cells in the adenohypophysis (anterior pituitary gland, And this gland now produces more prolactin to help deal with the large amount of testosterone circulating that hasn't bound to estrogen or androgen receptors.)

So more prolactin is produced to find a receptor, this excess prolactin triggers a process that fills the breast with milk via a process called lactogenesis, in men however it causes a distinct enlargment of the mammary gland and can even cause a man to lactate.

Prolactin influences upon androgen action in male accessory sex organs.
http://www.ncbi.nlm.nih.gov/pubmed/189591

Abstract
The hormones of the pituitary gland are capable of directly influencing the function of male accessory sex organs. Among these hormones, prolactin in particular has been observed to enhance consistently the effects of androgens in the prostate gland and/or the seminal vesicles of rats, mice, and guinea pigs as well as in the accessory sex organs of other species. Prolactin-mediated augmentation of testosterone's effects upon these tissues is related primarily to the growth-promoting influences of this steroid. However, under certain experimental conditions, the androgen-dependent production of secretions by these organs has also been enhanced by prolactin treatment. Studies in the mouse have indicated that prolactin primarily enhances the proliferative phase of androgen action in male accessory sex tissues. Testosterone stimulation of RNA synthesis was unaffected by simultaneous administration of prolactin. The mechanism by which prolactin causes enhanced androgen responses in the prostate gland and seminal vesicles is not well understood. It would appear, however, that prolactin neither stimulates increased accumulation of androgen into the accessory sex organs, nor does it enhance the conversion of testosterone to the more "active" androgen, dihydrotestosterone. The effects of prolactin on these tissues are, however, dependent upon the presence of dihydrotestosterone. Uncertain, at present, are the possible effects of prolactin on the binding or retention of androgens (dihydrotestosterone?) in the prostate gland or in the seminal vesicles. There is evidence that hypophysectomy reduces the nuclear binding of dihydrotestosterone in the cells of the prostate gland. Perhaps prolactin is a pituitary factor(s) which is important in regulating nuclear binding of dihydrotestosterone in male accessory sex organs. The direct influences of prolactin upon androgen action in the cells of the accessory sex organs may involve several sites of action (Figure 2). For example, it is currently understood that when testosterone enters the cell cytoplasm it is subsequently converted to the more "active" androgen, dihydrotestosterone (DHT), by reduction at the 5alpha position. Dihydrotestosterone is then either bound to a cytoplasmic "receptor" protein (Rc) or is further metabolized to either 5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol (DIOL). The binding of DHT to its cytoplasmic receptor protein results in translocation of the steroid-receptor complex into the nucleus where presumably the complex dissociates and DHT exerts its androgenic effects. The transport of DHT to the nucleus can also result from the conversion of testosterone to DHT by nuclear membrane-bound 5alpha-reductase. Prolactin augmentation of DHT effects is envisioned as resulting from interaction of prolactin with its receptor, which due to the large size of the prolactin molecule is probably located in or on the plasma membrane...

[Lotus]

For the GG's, PCOS,

Caution-technical info ahead, but hey, I put the eck in ech (aka-t'ech'nical, lol).



PCOS is a complex disorder of unknown etiology, and it involves several specialists for presenting reproductive, endocrinologic, dermatological, gynecological, cardiac and psychological implications.

Hyperinsulinemia seems to be one of the main factors responsible for steroidogenesis deregulation.

The variable and heterogeneous clinical picture makes diagnosis of PCOS difficult and tends to delay management that could avoid late complications.

Its treatment is preventive and aims to maintain the endometrial healthy, to antagonize the actions of androgens in target-tissues, to reduce insulin resistance (IR) and to correct anovulation. In addition to combined contraceptives and antiandrogens, the insulin-sensitizing agents are effective in preventing diseases associated with hyperinsulinemia. It is difficult to explain the therapeutic success of metformin in reducing insulin and androgen levels, as observed in some studies. It may be related to genetic variations, body weight, life style, duration of treatment and dosage of the drug.

Today, in order to avoid late complications, the specialists share investigations, trying to understand the etiology and pathophysiology of PCOS, which are essential for its treatment. The main focus of these studies has been several genetic and environmental determinants of the syndrome, for reflecting its heterogeneous phenotype.


The androgens derive from cholesterol and, in females, are synthetized by the ovaries, adrenal glands and in extraglandular sites of steroid conversion (liver, muscles, skin and adipose tissue).29,30 Androgen aromatization occurs in muscle and adipose tissues, that is, testosterone (T) and androstenedione (A) are converted into estrogens - estrone and estradiol, whereas, in the pilosebaceous unit and skin, T is converted into dihydrotestosterone (DHT) by the enzyme 5-alpha-reductase 1 or 2 (Figure 1B).29

The pilosebaceous unit and skin represent target-structures for androgen, which explains the pathophysiology of hyperandrogenism cutaneous manifestations (hirsutism, acne, seborrhea and alopecia).2

3-alpha-androstenediol glucuronide (3a diol G) derives from the conversion of DHT and A, by means of 5a-redutase. It is considered a marker of androgen biological action in the pilosebaceous unit, and the skin its main production site.2,4,29,30

Androgen biosynthesis (Figure 2) is mediated by cytochrome P-450c-17, an enzyme with 17a-hidroxylase, 17, 29-lyase and 17b-hydroxysteroid dehydrogenase (17b HSD or 17b R) activities. The androgens (A and T) are aromatized to estrone by the enzyme aromatase (cytochrome p-450 aromatase).27,29,31


In the ovaries, the androgens are precursors of estrogens and their production is controlled by LH/FSH (Figures 1Aand 2, and Chart 2).29,30,32 Normal ovarian function is determined by a combined action of LH in the theca cells, corpus luteum and stroma, and of FSH in granulosa cells.28

3. The role of insulin

Insulin is a polypeptide secreted by b-cells of the pancreas, and play an important role in glucose homeostasis.4,19,31 The classic target tissues include liver, muscles and adipose tissue. The terms insulin sensitivity and insulin resistance (IR) refer to the action of insulin in glucose homeostasis.4,19,31



4. Peripheral increase in cortisol metabolism

Increased androgen production by adrenal glands is observed in 25% of PCOS patients,70 probably as a result of genetic influence or secondary to abnormal secretion of ovarian androgens.31,65



Hyperandrogenism and skin: polycystic ovary syndrome and peripheral insulin resistance*

http://www.scielo.br/scielo.php?pid=S0365-05962005000400011&script=sci_arttext&tlng=en

[Lotus]

Interesting, this study claims Vitamin D increases aromatase activity.
____________________________________
Sunday, May 29, 2011
Vitamin D and Testosterone. Sunshine Vitamin Not So Manly, After all? Vitamin D Increases Aromatase Activity in Sertoli Cells

Vitamin D is all the rave. Even mainstream nutritionists are now jumping on the vitamin D bandwagon and the hype is spilling over from the Internet to newspapers and TV stations. "Take your Vitamin D!" is what children and adults, men and women, couch-potatoes and top-level athletes are told. Recently discovered problems related to the accurate measurement of actual vitamin D levels aside (e.g. Shah. 2011), a recent investigation into the immediate effects of vitamin D on aromatase activity in Sertoli cells of rat testes, suggests that we have to reevaluate whether this advice, which is hitherto largely based on epidemiological data, is not overgeneralizing, to say the least.


After all, the results of the aforementioned study, which has been published in the Journal of Vertebrate Reproduktive Science & Technology (Zanatta. 2011), clearly indicate that, contrary to common believe, your testosterone levels will not benefit from high vitamin D levels. On the contrary, in their in-vitro study Zanatta et al. found that incubation of Sertoli cells with 100nm 1,25D "increased the amount of aromatase transcript [...] in [Sertoli cells of] 30-day-old rats". Additionally, the scientists were also able to show that the increased aromatase activity was not exclusively due to a genomic effect, but was mediated via a "non-genomic activation of the membrane-bound vitamin D receptor involving the PKA pathway". Whether this is a tissue-, rat- or even age-specific effect does yet still warrant further investigation.
The latter is especially true in view of conflicting data on the effects of vitamin D on aromatase activity in especially in view of previous studies such as Lundgvist 2011 et al. (Lundgvist. 2011) who found that
In breast cancer MCF-7 cells, aromatase gene expression and estradiol production were decreased, while production of androgens was markedly increased. In NCI-H295R cells, 1α,25-dihydroxyvitamin D(3) stimulated aromatase expression and decreased dihydrotestosterone production. In prostate cancer LNCaP cells, aromatase expression increased after the same treatment, as did production of testosterone and dihydrotestosterone. In summary, our data show that 1α,25-dihydroxyvitamin D(3) exerts tissue-specific effects on estrogen and androgen production and metabolism.
So, will taking supplemental Vitamin D3 (1,25D) transform you into a hermaphrodite? Will you get rid of gynecomastia (gyno), but develop testicular cancer? The answer to both questions is probably "NO" And I am by no means suggesting that you extrapolate the rat data from isolated sertoli cells to human beings, but In view of these findings, it is nevertheless becoming increasingly questionable whether the correlations between testosterone and vitamin D that have been observed in epidemiological studies have not been misinterpreted as causative, where in fact, both, higher testosterone, as well as vitamin D levels, are a mere results of confounding variables such as an overall healthier, more active lifestyle. After all, our previous understanding of the connection between vitamin D and testosterone could have been as misleading as the idea that firetrucks cause fire, because an "epidemiological" investigation of fires would show that they are present whenever ones breaks out.


http://suppversity.blogspot.com/2011/05/...shine.html

[Lotus]

Sooo, lots of new research to share, (maybe too much, lol)

Here's some interesting research collected,

• Progesterone inhibits prolactin, estrogen receptors and aromatase, also DHT (we already knew that though).
  
  
• 5 alpha reductase inhibits progesterone receptors.
  
  
• Synthetic hormones bind to the wrong receptors, those receptors may convey inaccurate signals, which throws the body off balance.
  (This is why BCP’s cause so many hormonal imbalances and side effects).
  
  
• Estradiol in part regulates progesterone production physiologically and blocks progesterone production in a pharmacological or pathological state in the human corpus luteum.
  
  
• Forskolin and dibutyryl-cyclic AMP-stimulates progesterone production.
  
  
• Omega-3 fats, a polyunsaturtated type of fat, is high in testosterone.
  (Omega-3 fatty acids contribute to testosterone conversion and production as well as muscle protein synthesis. Seeds such as flax seeds provide healthy fats, including omega-3 fatty acids).
  
• Follicle granulosa cells have FSH-sensitive aromatase activity and proliferate in response to estrogens.
  
• Indole-3-carbinol selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cells.
  

More to follow-

[Lotus]

♦ Genetic males produce progesterone, but about half the amount of females. Progesterone is made in men by the adrenal glands and testes. Progesterone is vital to good health in both women and men.

♦ During the aging process, progesterone levels fall in men, especially after age 60. Progesterone is the chief inhibitor of an enzyme called 5-alpha reductase that is responsible for converting testosterone to dihydrotestosterone (DHT).

♦ When the level of progesterone falls in genetic males, the amount of conversion from testosterone to DHT increases.

[Lotus]

♦ Studies demonstrate that ERβ-mediated estradiol actions are vital to FSH-induced granulosa cell differentiation.

♦ Protein interaction between ER alpha and ER beta was demonstrated in vitro by GST pull-down assay and in vivo by immunoprecipitation. Thus, this study indicates that ER alpha and ER beta can interact in vivo, cross-signaling each other.

♦ Studies on large doses of fenugreek on four target organs—the liver, stomach, kidney and small and large intestine—reveal that the liver is the only one affected by the high doses. (Although anything in high doses isn't a good idea to begin with, why take the risk).

Animal research on fenugreek toxicity reveals that very large doses of the herb can lead to mild hepatitis according to Aziza M. Hassan, lead author of a study published in the "African Journal of Biotechnology."


   

Clinical Studies on Fenugreek.
http://www.arthmender.com/clinical_studies/fenugreek

Fenugreek Benefits for Men
http://www.livestrong.com/article/513411...s-for-men/

Libido enhancement supplements produced from fenugreek claim to increase sexual desire and performance in men. In a study published in the February 2011 issue of “Phytotherapy Research,” researchers recruited 60 men between the ages of 25 and 52 years without a history of erectile dysfunction and supplemented them with either a placebo or 600 milligrams of fenugreek extract per day for six weeks. The participants self-evaluated their satisfaction with fenugreek and reported that the supplement had a positive effect on libido. The study found that fenugreek extract had a significant influence on sexual arousal, energy and stamina and helped participants maintain a normal testosterone level.




♦ If estradiol is around in high enough dosages, it can bind to progesterone receptors and androgen (male hormone) receptors as well as to estrogen receptors

[Lotus]

(From the earlier post on progesterone)

♦ Progesterone reduces the aromatization of testosterone to estrogen. More progesterone thus generally means less estrogen, especially in men.

♦ Yet less estrogen can also reduce the effects of progesterone itself, because estrogen and progesterone strongly interact via cross-talk at both the estrogen and the progesterone receptor sites.