[Lotus]

Son of a gun, or (SOB)........I was right modifying genes does promote (advance) GID symptoms..... Clearly, this does give weight why we see a progression of guys wanting boobs to the decision of transitioning, and it ties to inhibiting CYP17, you know, the enzyme upstream where testosterone synthesis begins.



J Sex Med. 2015 Jun;12(6):1329-33. doi: 10.1111/jsm.12895. Epub 2015 Apr 29.
The CYP17 MspA1 Polymorphism and the Gender Dysphoria.

Abstract
INTRODUCTION:
The A2 allele of the CYP17 MspA1 polymorphism has been linked to higher levels of serum testosterone, progesterone, and estradiol.
AIM:

To determine whether the CYP17 MspA1 polymorphism is associated with transsexualism.

METHODS:
We analyzed 151 male-to-female (MtF), 142 female-to-male (FtM), 167 control male, and 168 control female individuals. Fragments that included the mutation were amplified by PCR and digested with MspA1. Our data were compared with the allele/genotype frequencies provided by the 1000 Genomes Data Base, and contrasted with a MEDLINE search of the CYP17 MspA1 polymorphism in the literature.

MAIN OUTCOME MEASURES:
We investigated the association between transsexualism and the CYP17 MspA1 polymorphism.

RESULTS:
A2 frequency was higher in the FtM (0.45) than the female control (0.38) and male control (0.39) groups, or the MtF group (0.36). This FtM > MtF pattern reached statistical significance (P = 0.041), although allele frequencies were not gender specific in the general population (P = 0.887). This observation concurred with the 1000 Genomes Data Base and the MEDLINE search.

CONCLUSION:
Our data confirm a sex-dependent allele distribution of the CYP17 MspA1 polymorphism in the transsexual population, FtM > MtF, suggestive of a hypothetical A2 involvement in transsexualism since the allele frequencies in the general population seem to be clearly related to geographic origin and ethnic background, but not sex.
© 2015 International Society for Sexual Medicine.

[Lotus]

In other words, this confirms GID symptoms can be elevated by a suppression of T. So what are the things that inhibit the CYP17 enzyme, (plenty), the Pharma anti-fungal ketoconazole inhibits (strongly I might add) CYP17 enzyme. And guess what?, green tea, lemons inhibit CYP17.........amazing.

[Atom]

Cool, you're dailed in on this, I will enjoy reading it. But the preliminary indications (imo) is that's it's more than just a dual (type 1 and type 2) Inhibitor, meaning it also inbitis C17 in the sebum (via the sebaceous gland),

great stuff. Thanks

The primary component appears to be a chemical called embelin, which a number of studies have done to asses its anti-androgen abilities for treatment of prostate conditions, acne, and also as a contraceptive for women. Some studies like the one below on rabbits say that progesterone increased as well, while other another study I saw on female rats said that progesterone and estradiol was lowered, which they believed to be due to an effect on the ovaries, but overall I couldn't find anything significant one way or another on how it would effect estrogen in humans, and from I can tell there have been contradictory results on how and if it affects estrogen. (The one where the study on female rats is mentioned - A REVIEW ON THE PHARMACOLOGY OF EMBELIA RIBES BURM.F. A THREATENED MEDICINAL PLANT http://goo.gl/DTCcqM )

This next one is a study on male rabbits

Changes in the concentrations of testosterone, luteinising hormone and progesterone associated with administration of embelin.

Githui EK1, Makawiti DW, Midiwo JO.

The mode of action of embelin, a naturally occurring plant benzoquinone with male fertility regulating potential, was investigated. Sexually mature white New Zealand male rabbits were injected intra-muscularly with embelin (30 mg/kg body wt) on alternate days for 14 days (7 injections). Blood was collected on alternate days over 27-day period from the beginning of embelin administration. Testosterone and progesterone levels were measured by radioimmunoassay and luteinising hormone (LH) by mouse interstitial cell testosterone bioassay. There was a marked reduction of testosterone concentrations within two days of embelin administration and up to 90% reduction by the 6th day. LH showed a corresponding rise with the falling testosterone levels. Similarly, there was rapid increase in progesterone levels with the administration of embelin. Both the concentrations of progesterone and LH declined when embelin dosage was stopped. Evidence from the observed changes in the levels of the three hormones suggest that embelin disrupts production of testosterone at the testicular level.

[Lotus]

Cool, you're dailed in on this, I will enjoy reading it. But the preliminary indications (imo) is that's it's more than just a dual (type 1 and type 2) Inhibitor, meaning it also inbitis C17 in the sebum (via the sebaceous gland),

great stuff. Thanks

The primary component appears to be a chemical called embelin, which a number of studies have done to asses its anti-androgen abilities for treatment of prostate conditions, acne, and also as a contraceptive for women. Some studies like the one below on rabbits say that progesterone increased as well, while other another study I saw on female rats said that progesterone and estradiol was lowered, which they believed to be due to an effect on the ovaries, but overall I couldn't find anything significant one way or another on how it would effect estrogen in humans, and from I can tell there have been contradictory results on how and if it affects estrogen. (The one where the study on female rats is mentioned - A REVIEW ON THE PHARMACOLOGY OF EMBELIA RIBES BURM.F. A THREATENED MEDICINAL PLANT http://goo.gl/DTCcqM )

This next one is a study on male rabbits

Changes in the concentrations of testosterone, luteinising hormone and progesterone associated with administration of embelin.

Githui EK1, Makawiti DW, Midiwo JO.

The mode of action of embelin, a naturally occurring plant benzoquinone with male fertility regulating potential, was investigated. Sexually mature white New Zealand male rabbits were injected intra-muscularly with embelin (30 mg/kg body wt) on alternate days for 14 days (7 injections). Blood was collected on alternate days over 27-day period from the beginning of embelin administration. Testosterone and progesterone levels were measured by radioimmunoassay and luteinising hormone (LH) by mouse interstitial cell testosterone bioassay. There was a marked reduction of testosterone concentrations within two days of embelin administration and up to 90% reduction by the 6th day. LH showed a corresponding rise with the falling testosterone levels. Similarly, there was rapid increase in progesterone levels with the administration of embelin. Both the concentrations of progesterone and LH declined when embelin dosage was stopped. Evidence from the observed changes in the levels of the three hormones suggest that embelin disrupts production of testosterone at the testicular level.

Ok thanks,

The surge of LH- llutenizing hormone(s) is generally temporary, why?, imo its a feedback control (hemostasis) when LH is being suppressed. When the surge is over, the signaling to the hypothalamus to produce more T is suppressed, in other words, testes get shut down. GnRH analogues causes this flare too.

https://en.m.wikipedia.org/wiki/Gonadotr...ne_agonist

http://www.sciencedirect.com/science/art...3406001027

[Lotus]

How preposterous would it be if I suggested I found a protein in PM that promoted dimorphism in males?..........but let's say it's more like dysmorphia........and btw, you know I f***ing did.

[Marcy]

I'm very curious to learn more about this new discovery! I do my best to keep up with your discoveries, but I must admit, it is a rigorous adventure!

[Lotus]

I'm very curious to learn more about this new discovery! I do my best to keep up with your discoveries, but I must admit, it is a rigorous adventure!

Well then, who doesn't like a good adventure.


Here's the thing, I think what I'm about to explain (in my mind) explains why for many of us (males) find PM so addictive. This protein (rather, an enzyme) in PM called CYP2B9 (part of the family of cytochrome P450 enzymes) expresses the dysphoria in two ways, (Liver and Brain).

I'll toss the science up after this post, It'll be massive and won't make a bit of sense, lol I won't be offended if you don't read it. however, the links (dotted lines) are there if anyone cares to do the reading.

The one study I listed the other day about CYP17 and gender dysphoria got me thinking, what if it (dysphoria) existed in any supplements we took.......and gues what?..........presto.........it's in PM. Granted, it led me on a preposterous pathway that would put folks to bed, but...........I'm an insufferable insomniac.

[Lotus]

This process takes place in two places, in the liver and the brain.


In estradiol, it induces expression of CYP2B9 , deoxymiroestrol -also induces the expression of CYP2B9. In the liver CYB2B9 (an enzyme (or protein) in the family of cytochrome P450 enzymes) is expressed. PM expresses this enzyme CYP2B9, which induces the expression of Growth Hormones. This expression signal is picked up by the hypothalamus, which then secretes growth hormones (e.g. glucocorticoid hormones) which escalates the dysphoria (aka GID).




Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver
http://www.sciencedirect.com/science/art...3X0500555X



Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice: Endocrinology: Vol 156, No 3
http://press.endocrine.org/doi/pdf/10.1210/en.2014-1429


Frontiers | Sexual Differentiation of the Rodent Brain: Dogma and Beyond | Neurogenomics
http://journal.frontiersin.org/article/1...00026/full


female-specific murine Cyp2b9 gene expression by growth or glucocorticoid hormones.
Sakuma T1, Kitajima K, Nishiyama M, Mashino M, Hashita T, Nemoto N.
Author information

Abstract
CYP2B9 is a constitutively and female-specifically expressed P450 isoform in mouse livers. Hypophysectomy-induced CYP2B9 mRNA expression in males to a level similar to that in females, while the operation did not affect females. Twice-daily injection of growth hormone (GH), which mimics the male pattern of GH secretion, significantly repressed hypophysectomy-induced mRNA expression in males. The same treatment completely suppressed expression in intact females. Treatments with synthetic glucocorticoid dexamethasone (DEX) suppressed expression of CYP2B9 mRNA in intact females, but not in GH-treated and un-treated hypophysectomized females. In primary cultured mouse hepatocytes, CYP2B9 mRNA expression was concentration-dependently suppressed by natural glucocorticoids such as hydrocortisone and corticosterone as well as by DEX. Glucocorticoid-mediated suppression was partially inhibited by RU486, a potent antiglucocorticoid. In contrast, RU486 by itself suppressed expression of CYP2B9 mRNA. These observations suggest that the sexually dimorphic expression of CYP2B9 is partly due to suppression by the masculine plasma GH profile and by glucocorticoid hormones.

Bimodal action of miroestrol and deoxymiroestrol, phytoestrogens from Pueraria candollei var. mirifica, on hepatic CYP2B9 and CYP1A2 expressions and antilipid peroxidation in mice —
http://www.ncbi.nlm.nih.gov/pubmed/22260863


A sexually dimorphic nucleus in the human brain | Science
http://science.sciencemag.org/content/22...2.abstract


Discriminating Activation of CYP2B9 Expression in Male C57BL/6 Mouse Liver by β-Estradiol
https://www.researchgate.net/publication...-Estradiol


Biological Evaluation of Deoxymiroestrol, a Potent Phytoestrogen from Pueraria candollei var. mirifica
Udomsuk L1, Putalun W1, Juengwatanatrakul T2, Jarukamjorn K1*
Introduction: Deoxymiroestrol is a phytoestrogen isolated from tuberous roots of Pueraria candollei var. mirifica (Leguminosae). Since deoxymiroestrol showed strong estrogenic-like activitiy, it is worth to investigate its biological activity on enzymes related drug metabolism, cytochrome P450s (P450), and sex hormone synthesis pathway, as well as its anti-lipid peroxidation in both in vitro in primary mouse hepatocytes and in vivo in mouse liver. Methods: P450 activities were evaluated in both primary mouse hepatocytes and mouse liver. Expression of CYP1A1, CYP1A2, CYP1B1, CYP2B9, AhR, and ARNT mRNAs were quantified by real- time RT-PCR while their activities were assessed by benzyloxyresorufin and methoxyresorufin O-dealkylation, respectively. Enzymes involved in sex-hormone synthesis pathway in male testes were semi-quantified by RT-PCR. Lipid peroxidation was measured in mouse brain. Results: In primary hepatocytes, expression of AhR, ARNT, and CYP1A1 mRNAs was suppressed whereas that of CYP1B1 was induced by deoxymiroestrol, in which the gene expressions were time- and concentration-dependent patterns compared to those of estradiol. In vivo in mice, deoxymiroestrol enlarged female uterus-weight and -volume as comparable to estradiol. As estradiol did, deoxymiroestrol induced expression of CYP2B9 mRNA whereas those of CYP1A2 were suppressed. Assessment of testicular enzymes involved in sex hormone synthesis pathway showed suppression of 3β-HSD, 17β-HSD1, and CYP17 expressions with those of CYP19 mRNA was slightly decreased by deoxymiroestrol. In addition, the expression of 17β-HSD2 was increased resulting in decreasing estradiol synthesis as that noted by estradiol. In addition, deoxymiroestrol possessed anti-lipid peroxidative activity in mouse brain. Conclusion: These observations suggested deoxymiroestrol as a potential alternative medicine for estradiol according to its distinctive abilities on regulation of related hepatic P450 enzymes and sex hormone-synthesis responsive enzymes, with its beneficent anti-oxidative potential.
Keywords: CYP1A1, CYP1A2, CYP2B9, AhR, ARNT, CYP17, 3β-HSD, 17β-HSD1, 17β-HSD2, deoxymiroestrol, estradiol, primary mouse hepatocytes, anti-lipid peroxidation

----------------------------
as noted earlier:

The CYP17 MspA1 Polymorphism and the Gender Dysphoria.

Abstract
INTRODUCTION:
The A2 allele of the CYP17 MspA1 polymorphism has been linked to higher levels of serum testosterone, progesterone, and estradiol.
AIM:

To determine whether the CYP17 MspA1 polymorphism is associated with transsexualism.

METHODS:
We analyzed 151 male-to-female (MtF), 142 female-to-male (FtM), 167 control male, and 168 control female individuals. Fragments that included the mutation were amplified by PCR and digested with MspA1. Our data were compared with the allele/genotype frequencies provided by the 1000 Genomes Data Base, and contrasted with a MEDLINE search of the CYP17 MspA1 polymorphism in the literature.

MAIN OUTCOME MEASURES:
We investigated the association between transsexualism and the CYP17 MspA1 polymorphism.

RESULTS:
A2 frequency was higher in the FtM (0.45) than the female control (0.38) and male control (0.39) groups, or the MtF group (0.36). This FtM > MtF pattern reached statistical significance (P = 0.041), although allele frequencies were not gender specific in the general population (P = 0.887). This observation concurred with the 1000 Genomes Data Base and the MEDLINE search.

CONCLUSION:
Our data confirm a sex-dependent allele distribution of the CYP17 MspA1 polymorphism in the transsexual population, FtM > MtF, suggestive of a hypothetical A2 involvement in transsexualism since the allele frequencies in the general population seem to be clearly related to geographic origin and ethnic background, but not sex.
© 2015 International Society for Sexual Medicine.

KEGG ORTHOLOGY: K00512
http://www.kegg.jp/dbget-bin/www_bget?K0...9.9+R02211

[Lotus]

The bottom line,

this expression of CYP17 and CYP2B9 (maybe CYP2B10 too?) in dexymiroestrol can explain why some progress to the point of transition, it did for me in some respects. I think it ties into when we over express growth hormones it puts us over the top so to speak.

We can liken this to a flood, or cascade if you will of hormones we (males) haven't yet adapted to. In females this enzyme in PM has some effect, but not like what it does in males.

I doubt this hypothesis will get us males a "kitchen pass" (an excuse) for behaviors lol, but........ It's a start.

[missboobshirt]

So much happens on your thread when I go away for just a bit lol the excitment!

OO lotus is that your full areola? we have matching areolas lol! -does anime boobie squish- was that weird? LOL cept you seem to have more under boobie than me, I have to make a bank account so I can order NB, I am dying for more underboob