Presence of SRY on Y chromosome
***the prescence of SRY (gene) on the Y chromosome leads to SOX-9 (protein)
Organization vs. Activation of the Brain
***steroid hormones are important for organizing the brain and adult sexual behavior
***later they activate the brain after puberty
Organization vs. activation:
- Increase in testosterone goes into the brain and organizes the brain differently
- When hormones are present in adults, it will act on those systems to regulate the behavior
Organizational Effects
early in development (prenatal and parinatal)
- steroid hormones permanently order the structure and other tissues that lead to development of other structures
activation:
- later in life, when that person goes through puberty, tesosterone acts on those structures to influence behaviors
- ex: during puberty, sex hormones can activate sexual behaviors
**early hormone structure (organization) sets the stage for later hormone actions (activation)
Male and Female Rat Sexual Behavior
major differences between male and female rats
males sexual behavior = numbering the amount of times they mount the female
female = arching the back when the male mounts them
**behavior in rats is organize during development
XX and XY rat behavior
XX:
- Low levels of estrogen after a few days after birth
- If you gave a female high levels of estrogen and progesterone you would get high levels of female sex behavior
- Females will exhibit some low levels of tesosterone behavior (male)
XY:
- Present of SRY and formation of testes
- The testes secretes high levels of tesosterone on first day of life
- The brain is aromatized into estradiol
○ That causes organization of male cuircutry
○ *estrogen masculinizes the male rat brain during their first day of life
***if an animal is given testosterone early in life, they are more likely to show male sexual behavior and low levels of female sexual behavior (vise versa for females)
**Main differences:
- testes release tesosterone first day in life (the brain then gets aromatized to estrogen) and brain is masculinized
** The majority of behavioral phenotypes or physiological phenotypes that are skewed toward the male is because of estrogen receptors in the brain
***The exposure to hormones are very brief (within first 24 hours of life) can create a lasting effect on behavior that they show in adulthood
Video Notes - Rat Sex Behavior
**they compared areas of male and female brains
***the hypothalamus area in males is 5x bigger than the area of the hypothalamus in females
○ Rats and humans start out with potential to develop into female and male sex behaviors
○ The presence of testosterone during development changes the brains
○ Giving females an injection of testosterone gives the females, male sex behaviors
○ Ex: the female that is injected with testosterone will hump the other female
○ Ex: the female injected with testosterone will hump the male rat that was castrated that acts with female sexual behavior
Ex of Giving Androgens
if you give androgens, it will organize and then it will cause male sexual behaviors
organization: androgens exposed after birth
as animal ages, testes secrete very low levels of testosterone
animal goes thru puberty
activation: once animal goes thru puberty, the animal starts showing male sexual behaviors
Brain can be Maculnizied or Feminized depending on what it’s Exposed to
If testes are present, they release tesosterone
○ Testosterone isn’t bound by alpha-fetoprotein so the testosterone goes to the brain, then the brain is aromatized by estradiol, which causes masculinization in brain
newborn:
- high levels alpha-fetoprotein and then it drops
- Protects brain of expoisure of estrogen but it doesn’t block the androgen from getting to the brain
**female brain is shaped by low levels of estrogen (first week)
***second week of life is shaped by estrodial (still much lower levels)
Anatomic Sex Differences: Volume of tissue
*all of the antomical differences are driven by tesosterone and estradiol
volume = single injection of testosterone will masculinize the brain and make it bigger
differences in SDN: third ventircle
- the large nucleus is the male brain (the SDN is bigger in male brain than the female brain)
***This is because of androgen exposure (and estrogen exposure)
- Birth- males : they have tesosterone surge – causes larger SDN in males
Birth - females: low levels of testosterone, which causes smaller SDN in females
***giving estrogen causes a masculnized size of the nucleus in SDN
Androgen Exposure - Volume for Brains
**androgen exposure on the first few days of life
Males: have testosterone surge
- in adulthood, they have a large SDN
female: not given testosterone to small SDN
If given testosterone injection to female:
- this gives them a msculinized size of the SDN
**if you give the female the injection after the sensitive period, then they won’t have a masculinized size of SDN later in life
***need androgen exposure during sensitive period to masculinize the brain
- If you’re stressed during the sensitive period, more lasting effects
Anatomic Sex Differences: Cell Death - SDN
*all of the antomical differences are driven by tesosterone and estradiol
Cell death: if you have sex differences in volume, it could be due to cell death
*Males have larger volume of SDN because androgens alter cell death
- Tesosteroen on first day of life saves cells in the SDN
- Males have larger SDN and females get smaller one
- During development, they have the same SDN size
○ But the exposure to androgens, stops the cell death in the SDN which keep it big
***The estrogen blocks apoptosis
- These cells would have died in the SDN, unless they had androgen exposure which would have blocked cell death from happening
Fewer cells undergo apoptosis If they were given estrogen in this brain region
Cell Death in the AVPV
AVPV = other brain area
- Involved in regulating cycles in female rats
- Testosterone kills cells in this area (*testosterone doesn’t save cells everywhere)
- Lack of tesosterone causes larger AVPV
if you stain brain w estrogen receptors:
- The female has a lot more estrogen receptors than the males do
-***Females have larger AVPV then males
Androgen exposure or estrogen can decrease cell death in the preoptic death, but that same hormone in a nearby brain area can kill off cells
Anatomic Sex Differences: Connectivity
*all of the antomical differences are driven by tesosterone and estradiol
connectivity:
- Vasopressin cells project thru a lot of brain regions
- They also project deep into the brain (amygdala and BST) and the pituitary gland
**high levels of vassopressin in the bed nucleus of the stria terminalis in males
*vasopressin cells (more in the male due to androgen exposure) so more fibers going to the lateral septum which is related to aggression
**in females, fewer vasopressin cells so fewer fibers going to the lateral septum
Anatomic Sex Differences: Cell Morphology
cell morphology: how cells look and are different
Arcuate Nucleus:
○ There are spine were the synapsis can occur
○ Females have much more neural spines (driven by androgen and estrogen)
○ **if you castrate the male on the first day of life, that leads to increased spine formation (density)
— So we know that androgens are suppressing spine formation
○ **if you expose females to androgens, then they won’t have as many spines
opposite for glia:
- the intact male will have more stellate class 4
- females will have more of class 1
- if you give the female estrogen, it pushes the female toward the male phenotype
***females have less complicated glia structure (they have more spines, but their glia are less differentiated) — opposite for males
Glia:
- Glia changes synapses in neurons
- If you have stellate at glia, that inhibits synapse formation (which is why in males, fewer synapses)
- In females, their glia are less differentiated which allows for more synapses to occur
**neurons and glia move together/opposite in communicating (they’re related)
Anatomic Sex Differences: Expression of Protein
*if females are given estrogen or androgens cause progesterone receptors to form
Anatomic Sex Differences: Migration
Hormones can determine a little bit where cells are moving
*the cells start moving faster after the brain is given estrogen
Estrogen can increase movement of cells within the brain
- ***female brain can move faster than males under baseline, because sometimes the female produces estrogen to compensate
Anatomic Sex Differences: Neurogenesis
neurogenesis = cell birth
***estrogen increases in the hippocampus
Estrogen can kill cells but also cause them to divide (neurogenesis)
If estrogen was causing cell division to happen, Brdu would be in that cell
**A lot of neurogenesis occurs in the hippocampus
- In the hippocampus, the number of dividing cells (with Brdu) males have more neurogenesis occuring then females
- If you give females estrogen, then females and males have the same pattern
- If you give males estrogen, they already have estrogen, so nothing happens
***estrogen causes neurogenesis
environment can change neurogenesis:
-Exercise can increase BrdU expression – animals that run more will have an increase in neurogenesis
- Exercise might be protective of not getting alzheimers because there’s more blood flow here and more neurogenesis
Sex differences in cell death and cell birth/Summary
**sex differences in cell death, where estrogen can protect against cell death or cause cell death to happen (depends on where the cell is)
**if you’re in the preoptic area, estrogen is protective
summary:
- males have bigger SDN and smaller AVPV
- males have more vassopressin cells
- males have more progesterone receptors
- estrogen can increase movement of cells
- if you inject BrDU in estrogen, you can increase the cells in the hippocampus
Development of Testosterone
testsoterone gets released from the testes
*brain masculinization and defeminization
Epigenetics
our environment shapes our epigenome
epigenetic modifications are stable and heritable changes (across cell division) in gene expression and cellular function (doesn’t change DNA sequence though)
Genetics
DNA Size
if you took DNA out of cell and stretched it a lot, it would be very long
- now tiny when packed back in
Histones
Cell now organizes DNA in a tight, controlled way
○ Now you have tiny piece of DNA inside cell – now it’s hard to transcribe and turn on genes
Opening DNA
epigenetics = understanding opening and closing of DNA