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its all down to genetics
#11
Further information on the FOX gene:

https://www.researchgate.net/publication...rentiation
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#12
so the question is: 

Does the introduction of Fox gene laden bovine ovary pills , trigger the Changes that some see on Bovine ovary pills? 
does the harvesting of the bovine ovaries at certain times , rely on the amount of Fox at time of harvest? does this indicate why it works for some, and not for others? 

http://www.bioone.org/doi/abs/10.1095/bi...lCode=bire

FOXL2, a winged-helix/forkhead domain transcription factor, is a key gene involved in the differentiation and biological functions of the ovary. In a recent transcriptomic analysis, we found that [i]FOXL2[/i] expression in bovine caruncular endometrium was different from that in intercaruncular endometrium. In order to gain new insights into FOXL2 in this tissue, we determined the expression of this transcription factor during the estrous cycle and the establishment of pregnancy in cattle. The endometrial expression of [i]FOXL2[/i] did not vary during maternal recognition of pregnancy (Days 16–20). Using an in vivo bovine model and primary cell cultures, we showed that [i]FOXL2[/i] was not an interferon-tau target gene. Both [i]FOXL2[/i] transcript and protein were expressed from Day 5 to Day 20 of the estrous cycle, and their levels showed a significant increase during the luteolytic phase. A 2-day progesterone supplementation in heifers led to a clear down-regulation of FOXL2 protein levels, suggesting the negative impact of progesterone on [i]FOXL2[/i] expression. Immunohistochemistry data revealed the localization of FOXL2 in endometrial stromal and glandular cells. FOXL2 subcellular distribution was shown to be nuclear in endometrial samples collected during the luteolytic period, while it was not detected in nuclei during the luteal phase and at implantation. Collectively, our findings provide the first evidence that FOXL2 is involved in the regulation of endometrial tissue physiology.
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#13
FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development


http://www.academia.edu/16198858/FOXL2_a...evelopment

Is this the reason that bovine ovaries aromatize the androgens into estrogen?
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#14
so, to link up some theorhetical info: ( this was all highlighted and listed in my "interesting article"thread: 
Breast Nexum- Interesting Article Link

ovaries to testes article:

https://sciblogs.co.nz/code-for-life/201...t-mammals/
"Slightly more formally, this research shows that the ovary has to maintain constant suppression of the key testis development gene Sox9 by Foxl2; if not ovarian granulosa and theca cells change to become testicular Sertoli and Leydig cells, respectively."



"Uhlenhaut developed a strain of genetically engineered mice, whose copies of FOXL2 could be deleted with the drug tamoxifen. When she did this, she found that the females’ ovaries turned into testes within just three weeks. The change was a thorough one; the altered organs were testes right down to the structure of their cells and their portfolio of active genes. They developed testosterone-secreting Leydig cells, which pumped out as much of the hormone as their counterparts in XY mice. They only fell short of actually producing sperm. ..


FOXL2 also has a partner-in-repression – the oestrogen receptor, a docking molecule for the hormone oestrogen. The two proteins interact with one another and they cooperate to block Sox9.

There have been hints from many species that FOXL2 plays an important role in determining sex.

Also, I have found that the bovine ovaries do contain the FoxL2 gene, dependent on cycle of estrous, there gene expression is greater at certain times.
My thoughts on it all:

So, the question is: "if" it truly does aromatize the testosterone into estrogen via the introduction of FOXL2 at a dose-dependent range. Should one decrease the Testosterone initially to near female range, in order for the FoxL2 gene to "storm the castle" and take hold to work? Or, does actual levels of T not really matter?  I would think that if you can lower the range of testosterone, you might have a better chance of the FoxL2 gene found in the bovine ovary to work. Perhaps if your body gets used to the FoxL2/aromatization, you can eventually cut back on anti androgens and let whatever T would be left to produce, to aromatize into the E, that would be necessary. There may be a chance that the adrenal glands that contain the FoxL2, would also kick in.  I think, if the levels of T are left normal, there is too much of a chance for the male-level T to overpower the introduction of the FoxL2 gene, and it be just a waste of time to consume the FoxL2 laden bovine ovary supplement. The other question is : does the FoxL2 gene survive the dessication into the powder form, even though it is freeze-dried and ground?

Essentially in theory, if you continue to introduce the FoxL2, it should convert the testes into ovaries, since the deletion of FoxL2 turned ovaries into testes.Perhaps this is why there is a "permanent" change for those whom claim after 6 months of Transfemme. even though there is lack of evidence other than anecdotal. There is a possible science behind it, it one thinks about it. I am sure, if you could find and extract the FoxL2 gene specifically, turn it into a pharma-grade pill.. you could turn your own testes into ovaries, then it would just be needed to be stitched up inside where ovaries are supposed to go. 

The other thought that occurred to me , is that most who are on Bovine ovaries, state that their testes have shrunk, which also leads me to believe that they are turned into ovaries, since ovaries are considerably smaller than testes

Mind you, these are all speculations. Real-time laboratory scientific study would need to be performed. I am neither scientist, nor have the sufficient lab to perform  proofs on theory. 
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#15
http://www.isna.org/faq/y_chromosome

Want to know more? The following comes from ISNA’s Medical Advisory Board member Dr. Charmian Quigley:
SRY, discovered in 1989, is a small gene located at the tip of the short arm of the Y chromosome. So what does it do? Actually, like all genes, it does nothing except to act as a blueprint for a protein. In this case, the protein of the same name does funky things to DNA, like bending it and unwinding the 2 strands, so that other proteins can get in and attach themselves to other genes that are then turned on. So how did this gene get its reputation (and its name) as the “sex determining” gene?
As is pretty common in the world of genetics, this was because of some errant mice. Researchers in England took a laboratory-made copy of this gene and inserted it artificially into a female (XX) mouse embryo at a very early stage of development. The mouse was “converted” from female to male, so the gene must have been responsible – right? Well, maybe not. A few years later, a similar gene was found on human chromosome 17. When the important part of this gene was inserted into a female mouse embryo, the same thing happened. Voila! A male.
So now we have 2 genes that can turn a female into a male, and one of them is not located on the Y chromosome! How can that be? It turns out that SRY is probably just a facilitator that allows a more critical gene (or genes) to function, by blocking the action of another opposing factor. Can the magic of genetics do the opposite – turn a male into a female? Indeed it can. A gene on the X chromosome (the chromosome one typically associates with “femaleness”) called DAX1 when present in double copy in a male (XY) mouse, turns it into a female.
So now we have genes on the Y that can turn females with XX chromosomes into males and genes on the X that can turn males with XY chromosomes into females… wow! Maleness and femaleness are NOT determined by having an X or a Y, since switching a couple of genes around can turn things upside down.

In fact, there’s a whole lot more to maleness and femaleness than X or Y chromosomes. About 1 in 20,000 men has no Y chromosome, instead having 2 Xs. This means that in the United States there are about 7,500 men without a Y chromosome. The equivalent situation - females who have XY instead of XX chromosomes - can occur for a variety of reasons and overall is similar in frequency.



Have to find a way to turn on the DAX1 gene...
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#16
https://ghr.nlm.nih.gov/gene/NR0B1

The NR0B1 gene provides instructions for making a protein called DAX1. This protein plays an important role in the development and function of several hormone-producing (endocrine) tissues in the body. These tissues include the small glands located on top of each kidney (the adrenal glands), two hormone-secreting glands in the brain (the hypothalamus and pituitary), and the gonads (ovaries in females and testes in males). Before birth, the DAX1 protein helps regulate genes that direct the formation of these tissues. DAX1 also helps regulate hormone production in endocrine tissues after they have been formed.



Since it (DAX1), is found both in ovaries AND testes, I do not think it is specifically DAX1 that would be the "switch" to flipping the genes from male to female. It is also found on the adrenal glands.. so that furthers my thoughts  the FOXL2 gene is more in control than what I thought the DAX1 would do. 
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#17
interesting:

https://academic.oup.com/hmg/article/18/4/632/601371

"nicotinamide, the active form of the B3 vitamin and a non-competitive inhibitor of sirtuins (32), is able to induce an increase in FoxL2 expression/activity. Moreover, we also find that 11 BPES-causing mutations of FOXL2 have a tendency to upset the (positive and negative) feedback regulation balance, thus presumably inducing aberrant FOXL2 expression and activity levels, often in association with an impaired activation of the [i]MnSOD[/i] gene."


Furthermore:
Interestingly, we observed that the addition of nicotinamide to the cell culture medium induced a significant activation of FoxL2 promoter (∼1.9-fold), which indicates that, presumably through quenching SIRT1 (and other sirtuins) activity, nicotinamide upregulates FoxL2 transcription (Fig. 5E). In these conditions, we also observe an increase of the basal activities of the 2xFLRE-luc (∼1.8-fold) and 4xFLRE-luc (∼1.5-fold) reporters (Fig. 5E), which are specific sensors of FOXL2 cellular concentration and activity levels (37). Thus, the enhanced FLRE-luc reporter activity indicates that there is an increase in FOXL2 concentration/activity in KGN cells upon nicotinamide treatment. Interestingly, preliminary evidence suggests that the treatment of C57/B6 mice with nicotinamide can also lead to an upregulation of Foxl2 expression [i]in vivo[/i] (Supplementary Material, Fig. S3). As BPES in association with POF often results from heterozygous null mutations, finding a way to increase FOXL2 expression from the functional allele is of therapeutic relevance. In humans, nicotinamide toxicity has been found to be low even at daily doses as high as 1260 mg over 2 years (about a thousand times higher than the recommended daily intake; 47). Therefore, a potential upregulation of ovarian FOXL2 expression/activity by nicotinamide supplementation deserves further exploration [i]in[/i][i]vivo[/i].

nicotinamide, can be purchase on Amazon as a supplement.

so the question is: will taking this supplement upregulate the FOXL2, and create a change in the testes, to convert it to ovaries? I am still thinking that this FoxL2 is the way to go.. more research needed. 
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#18
https://pdfs.semanticscholar.org/92cf/d8ce49992073f865ffcf8465308c5b769bb8.pdf
eLife digest

In female mammals, granulosa cells in the ovaries help egg cells to grow and develop by secreting nutrients and estrogens—the female sex hormones. A protein called FOXL2 helps granulosa cells to develop and functions by binding to the DNA of the cells to switch certain genes either on or off. In humans, mutations in the gene that codes for the FOXL2 protein are associated with granulosa cell tumors and with a loss of female fertility in early adulthood. In addition, if the amount of FOXL2 is artificially reduced in granulosa cells in female mice, the cells take on many of the characteristics of supporting cells found in the testes of males. To investigate in more detail how FOXL2 works, Georges et al. grew mouse granulosa cells in the laboratory to identify the DNA sequences where FOXL2 will bind, and to uncover how this binding affects gene expression. Georges et al. conclude that FOXL2 orchestrates a network involving many different proteins that allows estrogen to be produced and used by granulosa cells; and in doing so these cells maintain their identity as ovarian cells. FOXL2 was also shown to work closely with the receptor proteins that detect the sex hormones, and which help to control whether particular sex-specific genes are switched on or off. One particularly important role of FOXL2 in granulosa cells is that it represses a gene called Sox9. By repressing Sox9, the granulosa cells do not transform into their counterparts normally found in testes. Although FOXL2 was previously reported to directly regulate the Sox9 gene, Georges et al. find that it also acts through other molecules, and that there are alternative ways in which it can do so. Although Georges et al. have established some of the ways that FOXL2 functions, this protein can work via other pathways; these will require further investigation to be fully understood.

FOXL2 is required for efficient estrogen signaling.The above-mentioned findings support our hypothesis that FOXL2 plays an important role in estrogen signaling. We therefore analyzed the transcriptomic changes following a 10 hr 17β-estradiol (E2) treatment of primary granulosa cells pre-treated for 24 hr with either anti-FOXL2 or control siRNAs. We considered as potential targets those genes in the microarrays whose expression displayed a foldchange >2 in the presence of E2. We found 41 genes responding to estradiol according to our inclusion threshold, 39 of which were activated and only 2 were repressed. This is in agreement with previous reports suggesting that ERs are mainly transcriptional activators

A feed-forward loop reinforces the impact of FOXL2 on granulosa cell identity To better understand the combined effect of FOXL2 and ESR2 on granulosa cell maintenance, we analyzed SOX9 expression at the protein level 48 hr after Foxl2 and/or Esr2 knockdown. As expected considering our transcriptomic analyses, we observed that SOX9 expression was upregulated in the absence of either FOXL2 or ESR2 (Figure 5A). SOX9 expression was much higher in the absence of both ESR2 and FOXL2. This confirms that estrogen receptors and FOXL2 co-regulate SOX9 expression (Uhlenhaut et al., 2009). Interestingly, our transcriptomic analyses indicate that FOXL2 is required for the expression of Cyp19a1 (encoding the rate-limiting enzyme in estradiol production) both in the presence (Figure 5B) and in the absence of hormones (Figure 5C). Thus, FOXL2 may allow both estradiol production and enable estrogen signaling in the same cells. These data suggest the existence of a coherent feed-forward loop in which FOXL2 stimulates both estradiol production and receptivity (i.e., ESR2 expression) that might be responsible at least in part for the maintenance of granulosa cell identity by repressing the testis determinant Sox9.

So: if we can upregulate the FOXL2 to suppress the Sox9, creating a feed-forward loop, can this in fact convert the testes into ovaries or ovotestes, and thereby create a self sufficient estrogen producing organ , and delete the reliance on external estrogens? i.e. synthetic hormones? 
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#19
remember: Adrenal glands also produce FOXL2...

https://bioinformaticsreview.com/2017072...y-failure/

When FOXL2 binds to SF1, it upregulates CYP19 aromatase expression and inhibits CYP17 expression which is mediated by unbound SF1. Therefore, FOXL2 plays a major role in balancing the levels of androgen (CYP17) and estrogen (CYP17). It has been observed that mutations in the SF1 lead to male-to-female sex reversal in humans [32] and FOXL2 missense mutation leads to female-to-male sex reversal in goats [33]. The interaction of FOXL2 with SF1 also upregulates Mc2r [34], which codes for an ACTH receptor required for steroidogenesis and adrenal gland development [1]. Upon interaction with ERα, it prevents the binding of ERα to PTGS2 promoter. Not much is known about the impact of the interaction of FOXL2 to ERα on another target of ERα [35].

SF1 gene: 
https://en.wikipedia.org/wiki/SF1_(gene)
Splicing factor 1 also known as zinc finger protein 162 (ZFM162) is a protein that in humans is encoded by the SF1 gene.[3][4][5]

Splicing factor SF1 is involved in the ATP-dependent formation of the spliceosome complex.[6


Sooo, now how to figure out how to mutate the SF1 gene.... The plot thickens... Big Grin Tongue
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