Lecture 3 Differences between the sexes, genes, chromosomes, and hormones Flashcards
how do the developing testis differentiate the reproductive tracts?
The developing testis secretes Testosterone which stimulates Wolffian duct
formation (future vas deferens) and a peptide Mullerian inhibiting hormone (MIH)
which causes the Mullerian duct to degenerate, leading to absence of uterus.
describe Alfred Jost’s experiments
looked at the differentiation of reproductive tracts.
Grafted testis onto one overy in rabbit foetus. female.
found that the Wolffian ducts were stimulated and Mullerian duct inhibited.
Later used crystalline implants of testosterone, they stimulated the Wolffian ducts but didn’t degenerate Mullerian ducts. Therefore must be at least 2 signals.
What are the Wolffian ducts?
give rise to the vas deferenes in males
what are the fillopian tubes?
Gives rise to the fillopian tubes in females
What does testosterone do in the developing reproductive tracts?
stimulates Wolffian duct
formation (future vas deferens)
What does MIH stand for and do?
Mullerian inhibiting hormone
causes the Mullerian duct to degenerate, leading to absence of uterus.
What is the Jost hypothesis?
Secretion of androgens and anti-Mullerian hormone
(AMH) by fetal testis during critical stages of developmentn accounts for the full range of sexually dimorphic urogenital traits observed at birth.
sexual differentiation of the brain and behaviour not a part, added later.
describe the ancestry of x and y chromosomes.
common ancestors
how have the x and y chromosomes changed over time?
y progressively eroded in size, x has taken genes via translocation.
How is maleness conferred?
by he SRY on the tip of the Y chromosome.
genetic mapping found it in (infertile males maybe?????)
how are mouse embryos?
sexually neutral
how is testosterone signalled?
SRY gene leads to sertoli cells to be differentiated.
they provide support for the germ cells.
Also signal for Leydig cells of testis, they produce testosterone.
Testosterone then acts on distal targets throughout the genome to initiate sexual differentiation (secondary sexual characteristics ie penis and brain development)
Describe the role of Sertoli cells
Secrete substances initiating meiosis
Secrete testicular fluid
Concentrate testosterone locally with androgen binding protein
Release anti-mullerian hormone – preventing formation of a female oviduct.
Protect spermatids from the immune system.
damage to sertoli cells can affect you how?
infertile, still normal appearance as leydig cells prod testosterone fine
how do XX germ cells fare in ovarian and testicular environments?
survive in ovarian, produce follicles.
die in testis
how do XO and XY germ cells fare in ovarian environment?
die, cannot produce follicles and germ cells die. Lack a double x dose, some x linked dosage mechanism must exist.
maybe 2xs render the cell sensitive to the cytotoxic effects of MIH????
how do we know about germ cells needing to match gonads to be fertile?
make chimera mouse embryo - undifferentiated.
match wrong gerd cells to gonads, infertile as a result.
XXY germ cells in testis?
also die.
Klinefelter’s syndrome.
anatomical location of germ, sertolie and leydig cells?
sertoli cells inbetween germ, leydig not in tubules themselves, in the space inbetween. LOOK UP
what are leydig cells?
steroid producing cells, testosterone.
what happens in the absence of the SRY switch?
xx cells lead to no differentiation to sertoli cells in early embryo, and therefore no leydig cells.
the default sex is female.
endocrine system remains inactive until onset of puberty.
how does the male endocrine system change?
active in third trimester of pregnancy, then inactive until puberty. i think
how is male genitalia regulated?
5α reductase, places a hydrogen bond and changes testosterone to 5-dihydrotesterosterone
what is the primary role of testosterone?
maintains germ cell production.
what is the primary role of 5DHT?
drives sexual differentiation, ie secondary sexual characteristics & other differentiation.
how does 5DHT act?
on a common receptop to testosterone, but much more potent and acts on different circuits as a result.
all the roles of testosterone?
Spermatogenesis
Testicular descent
Wolffian duct growth
Gonadotrophin hormone regulation
Differentiation of brain via oestrogen
all the roles of 5DHT?
External virilization
Maturation at puberty
describe the castrate.
scant pubic hair, small penis.
lack of androgen effect on long bone growth and continued growth.
small penis, as little to no testoesterone and therefore 5DHT.
pubic hair as generated by androgen with adrenal origin
study on eunichs?
korean, look at life expectancy. testosterone decreases life expectancy.
Describe Klinefelters.
XXY.
small testis, small penis, scant body hair
have low testosterone production, XX probably disrupts steroidagenesis.
no spermatozoa produced, XX germ cells cannot survive in testicular environment.
Mullerian duct absent, Wolffian present.
Describe XY disgenesis
XY, dysfunctional Y chromosome due to mutation on X which produces a suppressor protein.
male karyotype, but underdeveloped females appearance.
no testicular development, has ovaries but degenerate as streaks.
therefore no sex steroids.
no pubic hair or breasts, tall stature as absence of oestrogen.
has normal uterus and vagina.
Describe testicular feminization.
identify as woman.
doesn’t show until lack of puberty onset.
lack of androgen receptor.
can’t percieve testosterone.
big ol bitties as no testosterone signal capable of opposing oestrogen, depends on ratio between the two.
no uterus as MIH produced by testis.
testis do not descend as dependent on a testosterone signal which cannot be read.
vagina is short.
how is the aromatase system affected in testicular feminization?
Note: Such individuals have intact aromatase system: so testosterone can be converted to oestrogen in the brain. So, absence of overt masculine behaviour suggests that in humans, testosterone aromatisation may not be important for gender identity. This is in marked contrast to rodents.
Describe Turner’s syndrome
one X chromosome lost - XO, due to chromosomes pairing up late on spindle.
No oocytes and therefore no sex hormones.
Female.
no germ cells therefore no sex steroids. XX needed for germ cells.
Ovaries or streak gonads.
Mullerian ducts present as no MIH.
Wolfian ducts as no testerosterone to stimulate development.
no penis or breasts.
effects on behaviour, socially in particular.
Describe the Guevedoces.
Penis at 12 years of age.
high inbreeding increases chances, 2% in some communities. Turkey, dominican republic
at birth test not sufficient enough to prod much 5dht.
at puberty testosterone rise to sufficient levels to virilize the body, testes descend and penis develops.
5a reductase deficient as they carry a mutation, therefore cant synthesise 5DHT.
not knockout as that would make female phenotype.
prenatal exposure to androgens?
bad not sure how
the effects of testosterone at high doses?
lowered sex drive. acne. liver problems. prostate cancer. infertility as negative feedback shuts down LH/FSH.
