Unit 8 - Sex Determination

Hot Wheel play behaviors

• male vervet monkeys preer wheeled toys over plush

• female monkeys play with both no preference

Rough and tumble play in humans

• boys and girls engage in rougha dn tubmle play

• boys more likely to spend more time in rough adn tumble play

Play bheavior → testosterone in rhesus monkey

• pregnant femaly rhesus monkeys given testosterone

• female offspring develope masculinized genitalia

Results of play

• play behavior of androgen exposed females more similar to males

• tesotserone acts during development to make brain function more like male

Congenital Adrenal hyperplasia (CAH)

• disorder where adrenal gland produces androgens and NOT cortisol

• treated by dexamethosone and surgery

• early treatment leads to normal life

CAH and regular pathway + Dexamethaosone

Normal

Brain → pituitary gland → adrenal gland → cortisol → cortisol inhibits brain stimulation of adrenal galnd for cortisol

CAH

Brain →→ (strong stimulation)→→ pituitary gland →→ adrenal gland →→ androgen

• Brain strong stimulation b/c want ot make cortisol, but instead overproduction of adnrogens

• Dexamethasone = form of cortisol, tricks brain into thinking cortisol being made by adrenal and turns of pathway → stop cortisol production

  • indirectly turns off adrenal gland

Grisl treated for CAH - play behaviors and obserations, effect of androgen and play behavior

girls treated for CAH more liely to

• prefer male playmates, be tomboy

• reduce interest in infant care and prefer male-typical toys

• hard to assess environmental impact

Behaviorsla observation

• ]girls with CAH show masculinized aspect og paly behavior (prefer playing with boys) vs unaffected girls

• androgen exposure in development influence some play behaviors aspects in girls

Takeaways - Guevedoces and Androgen insensitivity

Guevedoces

• mutation in 5 alpha reductase → lack of DHT

• born appearing female but take amle appearance at puberty

Androgen insensitivity

• mutation in androgen receptor gene → don’t respond to 

• normal levels of T, DHT, and normal testes, XY

• physical appearance female since can’t respond to T or DHT

male and female SDN size - testosterone injection test and main takeaway

1) Male

• already have tesosterone spike around birth → typical large SDN

2) Female with no tesosterone

• no tesosterone at birth → small SDN

3) Female treated with T at birth

• large T surge at birth → large SDN

4) Female treated with T at adulthood

large T sruge as adult → small SDN

Main takeaway

• LARGE SDN DRIVEN BY TESTOSTERONE EXPOSURE IN EARLY LIFE

Pregnant rats treated with T and estradiol + main takeaway

Pregnant rats treated with

• oil (control

• Test

• estradiol (strong estrogen)

Resutls

• Females trreated with testosterone and estradiol → both developed large SDN

Main takeaway

• testosterone and estradiol have same effect on SDN size

• test converted to estradiol

• DOES NOT ACT THROUGH ANDROGEN RECPTRO → ACTS THRU ESTROGEN RECPTOR AFTER CONV TO ESTRADIOL

Steroid hromone receptors

• are trasncription factors

Old school kidney cells test process and limitations

Process

1) grow kidney cells in dish

2) divide cell to two groups, A) tunr on estrogen recptor and B) keep receptor off

3) Measure what gene are turned on

Limitations

1) Estrogen receptor work diff in brain and kidney

2) Difficult to mimic physiological condtions in dish

3) Old school cell culture method → pick genes to study in advance

ALL OF THE ABOVE ON TEST

Modern approach to see gene regualtion by steroid receptors

Involves

• antibody that bidns to estrogen receptor

• Brain samplke

• Access to genome seqeuncing

• skills to analyze data

CUT and RUN

CUT and RUN process adn Takeaway

CUTand RUN - unbiased method for identifying genes regulated by trxn factor

Process

1) get brain smaple

2) extract nuclei → DNA+TF

3) add anitibody → bidns to a TF

4) Cut DNA - DNA cutting enzme i attracted to antibody and cuts

• isolates DAN bound to estrogen receptor

• DNA seq to find out. what genes are

CUT and RUN takeaway

• method where antibody used to isolate DNA sequences bound to a trxn factor (EX; estogen receptor)

Zebra finch - chromosome and gyandromorph

• are gynandromorph → right side → male/testes, left sdie → female/ovary

• Males - ZZ chromosome, Female - ZW chromosome

• Sex chromosomes on differnet parts of brain

  • W chromosome → only on female side

  • Z chromosome - twice as dark on male side

Sex differnetiation - Area X and RA

Area X

• on female side - Area X large similar to male → suggest hormones produced on male side corss to female side to control AREA X

Area RA

• RA larger on male side than female side

• RA size not affected by hormone, impacted by hormone dependent mechanisms (ex: genes)