So I've had more and more trouble dealing with friends of friends on facebook reposting anti-LGBT memes or interviews, articles ect. Yes I know I should grow a thick skin or cut them out but so far I'm still not "out" despite my hair and earrings. I have a number of aquaintences through work across a large geographical area, so I see the more moderates and the bible thumpers both show up. I recently reacted to an article a local older business man posted that started out as an anaylsis of the last election then somehow the interviewee turned to calling "->-bleeped-<-", "subjective feelings" of individuals that should not have any special protections. So I just responded with a long really basic explanation that science had proved brain structure differences, ect. He responded by saying "science" has been argued for centuries and that XX/XY was fact and fact is what mattered. OK so here I know, how does genetics become a fact if it wasn't science, right?
?
My response was that the job of science was to find facts and that knowledge of facts changes over time as new facts are discovered. I mentioned how the world was once "known" to be flat based on the facts of the day. I also mentioned how if he had family in one of the LGBT groups that listening to the facts becomes easier otherwise its far to easy to put the "unusual" into the box of "undesireable". He did not respond to that one.
In this whole process I started thinking about gathering alot of the research I have done so far in understanding how people become people. How the body and brain develop. I had the idea that compiling a timeline of scientific fact could be useful in the right circumstances to deal with anti-LGBT messages, IF you are talking to an generally non extremist person who just sees the stuff in the news and finds it weird or funny. Maybe some would open their minds. With that preface story, here is what I have at this point. Please let me know if anyone thinks this is a good idea or not. I have a habit of running away with ideas that aren't always useful sooo.
Gender and sex development: how we all become who we are.
Development of physical sex and neural based gender identity is a far more complex process that many who only under stand the concept of XX / XY genetics would like to believe. Fetal development of humans and all mammals is an extremely complex string of events which must happen flawlessly for "normal" gender and sex to happen. Since the Y chromosome is the trigger for male differentation we will start there.
The Y Chromosome:
The Y chromosome is nearly void of anything but replicated genetic information. The exception is the presence of the gene SRY (Sex-Reversal Y). This gene creates a protein called the Testes Determining Factor (TDF). This is the only chemical that can begin the process to create a male child. A secondary gene SOX-9 is nessecary to work with the TDF protein created by the SRY gene. While lack of TDF protein will allow a secondary gene DAX-1 to down regulate gene SOX-9.
Sexual Formation:
Internal Organ Development:
In the beginning of development the gonads form as two sets of cells, forming two regions, a medulla and cortex. The absence of TDF will result in formation of ovarian tissues from the cortex. The presence of TDF will form testes from the medulla. In the male, the newly forming Sertoli Cells of the Testes will make Anti-Mullerian Hormone (AMH). The AMH hormone has two effects. To begin with it will stimulate formation of another Testis cell type, the Leydig Cells. These will begin secreting basic testosterone hormone.
What can happen:
First, a mutated SRY gene can create a perfectly fertile woman with XY genetics by not creating testes. A mutation on the cells receptor for TDF could also cause this. The opposite can also happen where a genetic XX man can develop if one of the X chromosomes from the father received a crossed over SRY gene during sperm generation.
Secondly, any interference with the activity of the TDF activity can cause a delay in the formation of testes cell and have already partially created ovarian tissues. Such a case is called Ovatesties. This can be from external chemical interference such as medications taken by the mother.
The next tissues I will discuss are both present in every fetus. These will form the male or the female organs except for the gonads. Both sets of tissues are formed and waiting by the 8th week.
Wolffian Ducts: These form the male ducts and vas deferns. These will fade away and be absorbed unless an androgen hormone such as testosterone and its much more powerful derivative DHT (dihydrotestosterone).
Mullerian Ducts: These will form oviducts, uterus, and most of the vagina. If AMH is not produced by the Sertoli teste's cells, then these will continue to grow and develop by default. AMH will otherwise cause these tissues to fade and be absorbed. Ovaries are not required for these tissues to develop. They are cell autonomous and are only stopped by the presence of AMH.
What can happen:
Genetic caused Androgen Insensitivity can cause the Wolffian ducts to partially or completely fade away. AIS (Androgen Insensitivity Syndrome) is a genetic condition that can cause mild to full insensitivity of the bodies cells to androgen hormones. AIS is related mutations of the X chromosome located gene AR (Androgen Receptor).
Secondly, chemical / medication caused blockage of AMH activity or late production of AMH can result in a born male child who has partial female internal organs such as a partial or complete uterus. Some cases have shown the uterus being connected through the large intestine.
All of these regulating hormone interactions must take place and have full effect early in fetal growth. Any delay in regulating hormones can allow tissues to develop beyond the point where the regulating hormone has its normal effect on them. In a normal scenerio the testes tissues have been formed by the 7th week. The ovarian tissues wait a bit longer but are formed by the 12th week of pregnancy. The regulating hormones are active much earlier than this to differentiate the cells into the proper tissues.
External Genitalia Formation:
Before sexual differentation occurs the outside tissues are the same for all babies. These are called the genital turbicle, labrioscrotal folds, and gental folds.
With the effect of the hormone DHT (dihyrotestosterone)
Genital turbicle forms glands and shaft of the penis
Labrioscrotal folds for the scrotum
Genital folds fuse and form the penile urethra.
Without the effect of the hormone DHT
Genital turbicle forms clitoris
Labrioscrotal folds form the labia majora
Genital folds for the labia minor and vaginal end
What can happen:
The hormone DHT is the masculizing derivitive of testosterone. However its formation requires the enzyme alpha5-reductase. Each molecule of DHT requires one molecule of alpha5-reductase and one free testosterone molecule to be formed.
Mutations in the gene producing this enzyme will feminize the exterior genital appearance. Degree of feminization / masculinzation depends on enzyme activity in producing DHT.
Secondly, any of the mutations to the AR gene will effect the degree of effect DHT has on the forming tissues.
Brain Formation:
The human brain develops in specific stages. Each region of the brain is associated with different functions of life, senses, body functions, instinctual drive, emotions, thought processes. Specific segments are influenced by the presence of the hormone DHT during their development. DHT has a direct impact on the volume of these regions, the count of neural cells, and the developed neural structure patterns. These differences create the different instincts, thought processes, and emotional handling of the male and female brain. There is a specific limited time for a segment to be in a state that can be affected by DHT. Once this stage is past that region is "hard wired" for life. The neural structures cannot be changed.
Regions known effected by androgen exposure:
Hypothalamus INH2 = 2x larger male brain, assoc sexual attraction/sexual preference/orientation in all mammals, 3rd trimester
Hypothalamus INH3 = 2.8x larger male brain, neuron count and structure differences, assoc maternal instincts in female brain, volume, neural structures found specific to the gender of the brain, 2nd trimester
Hypothalamus BSTc = = gender specific volume, number cells, number neurons
Hypothalamus preopticanterior region = gender specific volume, number cells, neuron structures
Massa Intermedia = 53% larger female brain
Anterior Commissure = 12% larger female brain
Corpus Callosum = size difference based on brain gender seen. 1 claim of being a clinical diagnostic location for gender of the brain, the corpus callosum interconnects the left and right hemispheres of the brain and many subsections.
Corpus Callosum, Splenium = shape is gender brain specific, this is the posterior part
Left Angular Gyrus = functions auditory, visual, language inputs
Left Inferior Parietal Lobe = section contains the Left Angular Gyrus, submarginal gyrus
Cortical Thickness = Cortical layer is thicker in female gender brain.
Left hemisphere: frontal, orbitao-frontal lobe, central sulcus, perisylvian region, paracental cortex
Right hemisphere: pre/post central gyrus, parietal cortex, temporal cortex, precuneus, fusiform gyrus, lingual gyrus, orbito-frontal gyrus
What can happen:
All of these regions require androgen hormones to be present during the specific development period. If the level of androgen is low the region will wire its neural structures in a female manner. It's also possible to be partially viralized by low amounts of androgen hormone creating a structure partly between the "normal" male and female neural structures.
AIS can result in low virilization as the cells are less able to be effected by androgen hormones.
Outside chemicals in the mother can effect this as well. One well known drug called DES (diethylstilbestrol) is a synthetic estrogen like chemical that was thought to help prevent miscarriage. In the late a960's it became associated with female children developing a rare vaginal cancer. In 1971 the US FDA counter-indicated it for miscarriage prevention as a direct treatment. This means miscarriage was no longer a "labeled" use of the drug. There is a good deal of evidence that pharma companies continued added lower does of DES to prescription prenatal vitamins. It was also not uncommon for doctors to continue to prescribe it directly. The FDA banned it in the year 2000 for human uses. In the decades before DES was tied to a higher than normal number of children born with ambiguous genitalia. There was also a large number of otherwise male looking babies with undecended testicles and other genital development issues. At the time no one considered it would have any effect on the brain, as phycologists were quite firm in assuring everyone that only by raising children did any gender differences result in their behavior. DES was found to fully activate all estrogen receptors and block the androgen receptor actively by 75% with a blood concentration of 1um (1micromolar).
Terms:
TDF = testes determining factor, a protein signal produced by a normal SRY gene that signals the undifferentiated gonad cells to form testes.
AMH = Anti-Mullerian Hormone, chemical signal that causes testes to form Leydig cells which will produce Testosterone hormone. Also causes the stop to growth in the Mullerian Ducts and eventual absorbtion.
Androgen = name for the group of testosterone like hormones.
Testosterone = the base hormone produced by combining enzymes and cholesterol.
DHT = dihydrotestosterone, the primary superactive masculinizing hormone. Required for sexual differentation of genitalia.
5a-reductase = alpha5-reductase, an enzyme which is needed to produce DHT from testosterone.
Aromatase = an enzyme which is needed to produce estradiol hormone from testosterone in the ovary.
Estradiol = the primary superactive estrogen.
SRY gene = gene which produces the TDF protein located on the Y chromosome.
AR gene = gene which controls the androgen receptor molecular structure in all cells.
SOX-9 gene = gene activated by the TDF protein.
DAX-1 gene = gene active with no/low TDF protein, surpresses SOX-9 gene activity.
