[Fighter365]

The testosterone doses were comparable to those used for testosterone replacement in hypogonadal males. Intracranial, whole brain, gray and white matter of the cerebrum, hypothalamus, and lateral and third ventricle volume changes in the transsexuals were compared with brain volume changes in nine male and six female healthy comparison subjects over a 1-year interval. 

Results: (See Figures 2 & 3) Compared with controls, anti-androgen + estrogen treatment decreased brain volumes of male-to-female subjects towards female proportions, while androgen treatment in female-to-male subjects increased total brain and hypothalamus volumes towards male proportions. (Research Article)

Conclusions: The findings suggest that, throughout life, gonadal hormones remain essential for maintaining aspects of sex-specific differences in the human brain.

Figure 2

Brain volume changes in male-to-female and female-to-male transsexuals. Changes in hypothalamus, total brain, third and lateral ventricle volumes in milliliters (mean change from 0 at first measurement in bars, 95% confidence interval in error bars, individual values in circles) in transsexuals following cross-sex hormone treatment as compared with age- and sex-matched healthy comparison subjects.

Figure 3

Brain volumes in male-to-female and female-to-male transsexuals just prior to treatment. Hypothalamus, total brain, third and lateral ventricle volumes at scan 1 in milliliters (mean volumes in bars, 95% confidence interval in error bars, individual values in circles) in transsexuals as compared with age- and sex-matched healthy comparison subjects (individual value of one control male’s lateral ventricle (62 ml) not printed).

The changes in total brain and hypothalamus volumes following cross-sex hormone treatment in the transsexuals were mirrored by changes in their third and lateral ventricle volumes, i.e. treatment with estrogens and anti-androgens in MTFs increased third and lateral ventricle volumes, whereas treatment with androgens decreased the third and lateral ventricle volumes in FTMs. This suggests that the total brain volume changes are at least in part due to changes in medial brain structures surrounding these ventricles (including, but not limited to, the hypothalamus, which lies in close proximity to the third ventricle). Considering that the effects were not specific for gray (neurons, glia) or white (myelinated axonal fibers) matter suggests that both alterations in nerve cells as well as in axonal fibers may be implicated in the anatomical brain changes following cross-sex hormone treatment in humans. It is not surprising that the influences of sex hormones on the brain were not limited to the hypothalamus, but were also expressed as changes in total brain size. Estrogen and androgen receptor mRNA containing neurons are not limited to the hypothalamus, but are distributed throughout the adult human brain (18).


(18)Simerly RB, Chang C, Muramatsu M & Swanson LW. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situhybridization study. Journal of Comparative Neurology 1990 294 76–95.


Some Information on this. I found some posts about brain changes but noting as in depth as this. 
~Fighter365

[Lotus]

Some Information on this. I found some posts about brain changes but noting as in depth as this. 
~Fighter365

I love to see research posts (thanks so much). I wouldn’t say no depth into the brain changes in MTF/FTM posts here, it was covered here:

JulieTG's thread got me thinking about why people may decide on transition. In these studies I've listed previously prove that inhibiting GnRH (gonadotropin-releasing hormone) led to female neuron range. This 2012 study examines how estrogens modulate GH (growth hormone) in the liver and its impact on gender dependent dimorphism.

In other words, science indicates that when we start changing nuerons, estrogen metabolism in the liver (from using estrogens & phytoestrogens) it changes male neurons to female neuron range. 

So........imo this scernario influences this decision for transition. In the past I couldn't understand why many long term BN members went girlie, truth is my brain/liver " wasn't exactly ready (or there), and there being the female range. For some, the decision can't changed, or explained properly to loved ones. Shaming transtion is counterproductive / harmful to the trans individua0

The Influence of Estrogens on the Biological and Therapeutic Actions of Growth Hormone in the Liver

Abstract: GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-induced toxicity and fertility. In addition, estrogens can modulate GH actions in liver by acting centrally, regulating pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5 signalling pathway. Therefore, the interactions of estrogens with GH actions in liver are biologically and clinically relevant because disruption of GH signaling may cause alterations of its endocrine, metabolic, and gender differentiated functions and it could be linked to dramatic impact in liver physiology during development as well as in adulthood. Finally, the interplay of estrogens with GH is relevant because physiological roles these hormones have in human, and the widespread exposition of estrogen or estrogen-related compounds in human. This review highlights the importance of these hormones in liver physiology as well as how estrogens modulate GH actions in liver which will help to improve the clinical use of these hormones.

http://www.mdpi.com/1424-8247/5/7/758/htm

I wasn't convinced about a point of no return.  Turns out, science explains that certain motor neurons exposed to estrogens and growth hormones does promote dysmorphia. Another study (mouse) showed that PM had this same effect in the liver and brain......

I do believe certian proteins (e.g. STAT5) can have an effect too, in our brain and liver. Additionally, I'm certain will find another protein linked enzyme (from the CYP family of enzymes) that will explain another brain/liver/hypothalamus cross link. 

Male-to-female transsexuals have female neuron numbers in a limbic nucleus.
Kruijver FP1, Zhou JN, Pool CW, Hofman MA, Gooren LJ, Swaab DF.
Author information
Abstract
Transsexuals experience themselves as being of the opposite sex, despite having the biological characteristics of one sex. A crucial question resulting from a previous brain study in male-to-female transsexuals was whether the reported difference according to gender identity in the central part of the bed nucleus of the stria terminalis (BSTc) was based on a neuronal difference in the BSTc itself or just a reflection of a difference in vasoactive intestinal polypeptide innervation from the amygdala, which was used as a marker. Therefore, we determined in 42 subjects the number of somatostatin-expressing neurons in the BSTc in relation to sex, sexual orientation, gender identity, and past or present hormonal status. Regardless of sexual orientation, men had almost twice as many somatostatin neurons as women (P < 0.006). The number of neurons in the BSTc of male-to-female transsexuals was similar to that of the females (P = 0.83). In contrast, the neuron number of a female-to-male transsexual was found to be in the male range. Hormone treatment or sex hormone level variations in adulthood did not seem to have influenced BSTc neuron numbers. The present findings of somatostatin neuronal sex differences in the BSTc and its sex reversal in the transsexual brain clearly support the paradigm that in transsexuals sexual differentiation of the brain and genitals may go into opposite directions and point to a neurobiological basis of gender identity disorder.

In other words, men have twice as many hormone secreting neurons as women. This suggests that you (males) traveling down the NBE or pre hrt pathway may already, without realizing it, are predominantly in the female neuron range. (Just an opinion).

Haha, lol.....you've been warned.

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

[The First Aria]

I wonder if that is the reason I really don't feel more feminine, that I am still of Two Spirit is because I am NOT taking oral HRT but patches.  That is, except for my Progesterone is pill???

[Fighter365]

Some Information on this. I found some posts about brain changes but noting as in depth as this. 
~Fighter365

I love to see research posts (thanks so much). I wouldn’t say no depth into the brain changes in MTF/FTM posts here, it was covered here:

I stand corrected and you are most welcome!! Sometimes its hard find specific posts in the search and I hope with the title of this thread and your adding of knowledge will help others see how cross-sex hormones can really change brain chemistry. Thank you for putting that here! 

I can defiantly notice a change in my brain just being on and off PM and BO w/anti androgen's.  I finally comprehend what these headaches/Pressure were all about and this has been my longest streak thus far of taking them.  I'm finding it harder and harder to present as a male mentally and its obvious why.

This report was made in 2006 so its really nothing new, just reporting in on the sea of studies i come across and in my 2-3 active years of looking into NBE as I have never seen it and felt the impulse to share with you all.

Cheers, happy growing!

[The First Aria]

Some Information on this. I found some posts about brain changes but noting as in depth as this. 
~Fighter365

I love to see research posts (thanks so much). I wouldn’t say no depth into the brain changes in MTF/FTM posts here, it was covered here:

I stand corrected and you are most welcome!! Sometimes its hard find specific posts in the search and I hope with the title of this thread and your adding of knowledge will help others see how cross-sex hormones can really change brain chemistry. Thank you for putting that here! 

I can defiantly notice a change in my brain just being on and off PM and BO w/anti androgen's.  I finally comprehend what these headaches/Pressure were all about and this has been my longest streak thus far of taking them.  I'm finding it harder and harder to present as a male mentally and its obvious why.

This report was made in 2006 so its really nothing new, just reporting in on the sea of studies i come across and in my 2-3 active years of looking into NBE as I have never seen it and felt the impulse to share with you all.

Cheers, happy growing!

Still a good find.  I learn as much and sometimes understand better with graphs.  I guess that just means I'm still Neanderthal about technical jargon and no pics.  LOL

[Katie]

I wonder if this would explain why I have almost no memory of ever having being "male"?
in all my memories I`v always been like I am now and yet this clearly isn`t true? it`s like i`v Always been me and I can`t remember Not being me and my memories of childhood are really clear now too, better than they`ve ever been, and some things I have absolutely no memory of at all after puberty just patchy vague stuff but nothing clear or anything I can attatch to.
But... all the stuff I`v Learned over the years (acedemic stuff) seems to have stayed intact as far as I can tell.
and the really freaky part that would have scared the hell outa me pre transition is that I don`t care! LOL

[julieTG]

Flies in the face of the study last year where they said influence of cross sex hormones had zero effect on adult transgender brains ????

They claimed once brains are hard wired and that's it

Mind you after being on estrogen for 4 months Ish now cannot fully agree with that outlook, 

Julie
X

[Katie]

to be honest it`s not something you would ever really notice until something exposes it, and then it`s like "oh yeah! how odd".
there`s an online book called "so you want to be a T Girl?" although I don`t recommend anyone read it as it`s a bit dismisive of other folks under the Trans* umberella and downright rude to others that aren`t true transsexuals, but even in there it explains that the brain you start off with before HRT is Not the brain you end up with! or something to that effect.

so it`s either that or the experimentation I did with hypnosis last year has started working! LOL

[The First Aria]

I wonder if this would explain why I have almost no memory of ever having being "male"?
in all my memories I`v always been like I am now and yet this clearly isn`t true? it`s like i`v Always been me and I can`t remember Not being me and my memories of childhood are really clear now too, better than they`ve ever been, and some things I have absolutely no memory of at all after puberty just patchy vague stuff but nothing clear or anything I can attatch to.
But... all the stuff I`v Learned over the years (acedemic stuff) seems to have stayed intact as far as I can tell.
and the really freaky part that would have scared the hell outa me pre transition is that I don`t care! LOL

I think it just means Katie, that you have just re prioritized your memories.  Another word for it is justification, or selective memories.  It's sort of like a person that experienced something very traumatic, and somehow forgets everything from the starting point to waking up in the hospital.  It's a way to protect our sanity, not physical re wiring I suspect.