Lecture 3 (Louden)

Question 1

how do the developing testis differentiate the reproductive tracts?

Answer 1

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.

Question 2

describe Alfred Jost’s experiments

Answer 2

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.

Question 3

What are the Wolffian ducts?

Answer 3

give rise to the vas deferenes in males

Question 4

what are the fillopian tubes?

Answer 4

Gives rise to the fillopian tubes in females

Question 5

What does testosterone do in the developing reproductive tracts?

Answer 5

stimulates Wolffian duct

formation (future vas deferens)

Question 6

What does MIH stand for and do?

Answer 6

Mullerian inhibiting hormone

causes the Mullerian duct to degenerate, leading to absence of uterus.

Question 7

What is the Jost hypothesis?

Answer 7

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.

Question 8

describe the ancestry of x and y chromosomes.

Answer 8

common ancestors

Question 9

how have the x and y chromosomes changed over time?

Answer 9

y progressively eroded in size, x has taken genes via translocation.

Question 10

How is maleness conferred?

Answer 10

by he SRY on the tip of the Y chromosome.

genetic mapping found it in (infertile males maybe?????)

Question 11

how are mouse embryos?

Answer 11

sexually neutral

Question 12

how is testosterone signalled?

Answer 12

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)

Question 13

Describe the role of Sertoli cells

Answer 13

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.

Question 14

damage to sertoli cells can affect you how?

Answer 14

infertile, still normal appearance as leydig cells prod testosterone fine

Question 15

how do XX germ cells fare in ovarian and testicular environments?

Answer 15

survive in ovarian, produce follicles.

die in testis

Question 16

how do XO and XY germ cells fare in ovarian environment?

Answer 16

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????

Question 17

how do we know about germ cells needing to match gonads to be fertile?

Answer 17

make chimera mouse embryo - undifferentiated.

match wrong gerd cells to gonads, infertile as a result.

Question 18

XXY germ cells in testis?

Answer 18

also die.

Klinefelter’s syndrome.

Question 19

anatomical location of germ, sertolie and leydig cells?

Answer 19

sertoli cells inbetween germ, leydig not in tubules themselves, in the space inbetween. LOOK UP

Question 20

what are leydig cells?

Answer 20

steroid producing cells, testosterone.

Question 21

what happens in the absence of the SRY switch?

Answer 21

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.

Question 22

how does the male endocrine system change?

Answer 22

active in third trimester of pregnancy, then inactive until puberty. i think

Question 23

how is male genitalia regulated?

Answer 23

5α reductase, places a hydrogen bond and changes testosterone to 5-dihydrotesterosterone

Question 24

what is the primary role of testosterone?

Answer 24

maintains germ cell production.

Question 25

what is the primary role of 5DHT?

Answer 25

drives sexual differentiation, ie secondary sexual characteristics & other differentiation.

Question 26

how does 5DHT act?

Answer 26

on a common receptop to testosterone, but much more potent and acts on different circuits as a result.

Question 27

all the roles of testosterone?

Answer 27

Spermatogenesis

Testicular descent

Wolffian duct growth

Gonadotrophin hormone regulation

Differentiation of brain via oestrogen

Question 28

all the roles of 5DHT?

Answer 28

External virilization

Maturation at puberty

Question 29

describe the castrate.

Answer 29

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

Question 30

study on eunichs?

Answer 30

korean, look at life expectancy. testosterone decreases life expectancy.

Question 31

Describe Klinefelters.

Answer 31

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.

Question 32

Describe XY disgenesis

Answer 32

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.

Question 33

Describe testicular feminization.

Answer 33

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.

Question 34

how is the aromatase system affected in testicular feminization?

Answer 34

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.

Question 35

Describe Turner’s syndrome

Answer 35

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.

Question 36

Describe the Guevedoces.

Answer 36

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.

Question 37

prenatal exposure to androgens?

Answer 37

bad not sure how

Question 38

the effects of testosterone at high doses?

Answer 38

lowered sex drive.
acne.
liver problems.
prostate cancer.
infertility as negative feedback shuts down LH/FSH.