Disorders of sexual development Flashcards
Before what week is the sex of the fetus indistinguishable
before week 6
what happens to late germ cells? two things
1) Disintegrate
2) may develop into extragonadal tumors
male and female genital ducts are derived from what
mesonephrons
At what week does male internal genitalia begin development
week 8
-note female development starts at week 12
what cells secrete AMH
sertoli cells
-note AMH causes mullerian degeneration
what converts testosterone to DHT
5 alpa reductase 2
what hormone do you need for external male genital
DHT
what inhibits growth of vesicovaginal septum preventing the development of the vagina
DHT
what gene has one exon, GC-rich in 5’ region
SRY gene
SRY gene has 2 zince-finger rich recognition sites for what
Sp1
what part of the SRY gene binds to the minor grrove
HMG octamer in the protein
-Not high yield
An SRY mutation that deals with HMG octamer mutation will cause what
no binding to DNA, thus no male differentiation. So we get 46, XY female. This person looks like a girl, but has a Y chromosome
what drags the SRY over doing the crossing over phase, thus causing the SRY gene to be NOT on the Y chromosome
Pseudo Autosomal Region (PAR)
- this is a SRY translocation to X
- so 46, XX female but looks male, and 46, XY male that looks female
what two proteins are required in order to have SRY expression
WT-1 and SF1
Gonads and adrenal development require what protein
SF1 (steroideogenic factor)
-this allows sexual determination, sexual differentiation, steroidogenesis, lipid metabolism
what transcription factor mutation can cause camptomelia dysplasia
SOX9 mutation
-camptomelia dysplasia is 46 XY, sex reversal (cant determine the sex, in her words)
what mutation causes bowing of long bones, shortened long bones, and sketetal dysplasia like hypoplastic scapulae, narrowed iliac bones, chest hypoplasia (respiratory distress)
Campomelia dysplasia which is caused by SOX9 mutation.
-she says you cant determine the sex 46 XY (sex reversal)
what is SOX9’s only target, which if it doesnt hit we will get ovary development
Anti-mullerian hormone
-no SOX9, mullerian ducts do not degenerate
what attaches to serene-threonine protein kinases (single transmembrane domain)
Anti-mullerian hormone, which attaches to the mullerian duct and causes apoptosis
Mullerian (paramesonephric) ducts and Wolffian (mesonephric) ducts, which one is hormone-INDEPENDENT development
Mullerian
what is crucial for ovary development but not testes development. And a mutation or deletion of this will result in congenital adrenal hypoplasia and hypogonadotropic hypogonadism
DAX1 gene (on x chromosome) -she has that they would get testicular development occurs; 46 XX male (what she had on slide)
Duplication of this in males can cause 46 XY that has a stronger woman phenotype
DAX1. Note that duplication of DAX1 in females has no affect
-in the duplicated state there may be insufficient SRY to repress DAX1 expression
what are some ways we can get sex reversal
1) SRY mutation
- 46 XY females
- 46 XX males w/ SRY translocated to the X
2) SOX9 mutations
3) DAX1 mutations
No sex hormones or cortisol. Elevated production of mineralocorticoids. Phenotypically female but unable to mature. Is it 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase, aromatase, or 5alpha-reductase
17alpha-hydroxylase
