(09-05-2015, 12:25 PM)Trixy Wrote: Would anyone be willing to do a bit of a summary on the most noteworthy anti-androgens, their primary effects, important side effects and (roughly) recommended safe doses? A kind of pros vs cons for some of the more common AAs would be awesome.
I get that I could probably scrape this sort of information by reading through this thread, but seriously, it's 71 pages... I'd be grateful if someone who's been following this thread (or has knowledge on natural AAs from elsewhere) would write a kind of overview, or if such an overview already exists then direct me to it. Thanks in advance. <3
(09-05-2015, 11:27 PM)myboobs Wrote: Haven't seen jackp114 , post for a while here ! He seems to be doing a lot of herbal research [/i]
(10-05-2015, 12:42 AM)spanky Wrote: Fantastic summary, Lotus! Thanks as always to our resident sage.
(29-09-2014, 04:56 AM)Lotus Wrote:(29-09-2014, 03:55 AM)45-25-45 Wrote: 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.
(02-10-2014, 04:02 AM)Lotus Wrote:(02-10-2014, 03:48 AM)Lotus Wrote: 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/ncurrent/full/aps201418a.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
(28-04-2016, 02:12 AM)Lotus Wrote: I grew 2-3 cups using Reishi (w/no unfair advantages) 4+ cups overall with NBE. BO did not agree with me. Reishi coumarins ARE NOT the main bio actives that inhibitors 5 AR..........it's polysaccharides, triterpines, and other lipids are the main bioactives that does the inhibiting in the Prostate. Reishi has a 2,000 year track record, not sure how much more record keeping, accept HERE.........where it's used to grow breasts. Information (complete w/attached studies) continue to show the potential of reishi. I'll attach the related papers, (located in my project x thread). Btw Abi, none of your files are deleted, just moved here, so you and i dont hijack another thread, apologies for any inconvenience.
In many cases no lab research is related to NBE, or how it effects male breast growth. We are, in fact the lab test subjects to carry out the business of real world result (or not). FWIW.
Reishi has 5a-reductase inhibitory activity of more than 90% at 200 ug/ml.
5α-Reductase inhibitory activity-guided fractionation of the EtOH extract of the fruiting body of Ganoderma lucidum (LEYSS.:FR.) KARST. (Ganodermataceae), which is called Reishi, or Mannentake in Japan and Lingzhi in China, led to the isolation of two active compounds which were ganoderic acid DM and 5α-lanosta-7,9(11),24-triene-15α,26-dihydroxy-3-one with an IC50 of 10.6 μM and 41.9 μM respectively. A carboxyl group of side chain of ganoderic acid DM is essential to elicit the inhibitory activity because of much less activity of its methyl ester.
http://www.ncbi.nlm.nih.gov/pubmed/16462054
(29-09-2014, 04:56 AM)Lotus Wrote:(29-09-2014, 03:55 AM)45-25-45 Wrote: 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.
(02-10-2014, 04:02 AM)Lotus Wrote:[/quote](02-10-2014, 03:48 AM)Lotus Wrote: 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/ncurrent/full/aps201418a.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