[jannet.duff]

Great find ....

[myboobs]

That wrecked my brain but very interesting . My grand niece is doing her PhD in stem cell and had very interesting chat with her ?

[The First Aria]

Well all I know is that with Lotus's guidance, WP seemed to have jumped started me when I hit a major plateau.

[jannet.duff]

Well all I know is that with Lotus's guidance, WP seemed to have jumped started me when I hit a major plateau.

I actually just ordered some more WP, to assist with my HRT.

[Lotus]

That wrecked my brain but very interesting . My grand niece is doing her PhD in stem cell and had very interesting chat with her ?

That's cool MB, I'll bet you're proud of her. ( Lol, I can think of a few chats I'd have too ).

Great find ....

Thanks jannet.

Well all I know is that with Lotus's guidance, WP seemed to have jumped started me when I hit a major plateau.

it's two way street, you've help me too.

Well all I know is that with Lotus's guidance, WP seemed to have jumped started me when I hit a major plateau.

I actually just ordered some more WP, to assist with my HRT.

I hope it helps.

[Lotus]

Greetings BN.

This is an oversimplification on my part of β-cell regeneration (my apologies, please bear with me):

Insulin secretes β-cells from the pancreas, diabetes destroys these B-cells which results in the demand for insulin, and that's grime news to be quite honest (mortality).

Type 2 diabetes seems to be a bigger threat of losing β-cell volume (40 - 60%) according to one study, (obesity the driving factor).

The stem cell research replaces β-cells by regeneration. There's other protocols being studied as well, see below:

so......seeing that pro-inflammatory states in humans are the driving factors in most illness, I see starting with antioxidants as the first weapon (eliminating free radicals, cause they from the P450scc (cholesterol side-chain cleavage, in enzymes), then add LC-PuFA's (long chained fatty acids). Now, I don't if FAS (fatty acid synthase) or TNF (Tumor necrosis factor) which is another cell signaling protein (cytokine) is involved, though most likely is. In other words, does apoptosis regenerate cell types?, I'm gonna take a leap and say yes. This makes things like WP and EGCG (the Polyphenol in green tea) viable. ......and oh by the way, WP has epigallocatechin-3-gallate, also known as EGCG, the same polyphenol in green tea.

How to make a functional β-cell
http://dev.biologists.org/content/140/12...rticle-top

[Lotus]

In this study astaxanthin inhibits (or delays) β-cell destruction, in other words, preventing glucose overproduction, a 1mg dose of astaxanthin was used in the study. So what does tell about astaxathin that we didn't already know?, well......astaxanthin is 500x stronger than vitamin C, it inhibits DHT, protects against free radicals, inhibits DHT, promotes sperm (reminds me of a PDE5 supplement), protects against skin damage, etc.

astaxanthin may exert beneficial effects on pancreatic β-cell function in diabetes


Astaxanthin protects β-cells against glucose toxicity in diabetic db/db mice
http://www.cyanotech.com/pdfs/bioastin/batl19.p

[Lotus]

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

[elainecd]

Lotus, I read through this twice....if I understood correctly.....this is why, after over two years of PM and peony root extract, I have this female in me getting stronger and stronger. 
Now... I not only want to continue to HRT, I feel I NEED it.
She's hard to fight so it looks like its going to happen.

[Lotus]

Lotus, I read through this twice....if I understood correctly.....this is why, after over two years of PM and peony root extract, I have this female in me getting stronger and stronger. 
Now... I not only want to continue to HRT, I feel I NEED it.
She's hard to fight so it looks like its going to happen.

same here, after bombarding those neurons and liver with phyto's for close to 2 years I felt the need to switch to HRT (2 years sounds relative lol)......time frames differ though, right?. On the flip side, some are content without transition (that's cool too), though fighting that desire to have more is undeniable .