Endocrine Signalling 5

Question 1

What is androgen insensitivity syndrome

Answer 1

A disorder of sex development involving hormonal resistance due to androgen receptor dysfunction.

Question 2

What is kleinfelters syndrome and its presentation

Answer 2

XXY - produce less testosterone

Tall, infertile males, small testes and speech disabilities, impaired erectile function, mood disturbances

Question 3

What causes congenital adrenal hyperplasia

Answer 3

Autosomal recessive disorders -
enzyme deficiencies for adrenal steroid hormones (21-hydroxylase deficiency in 95%) this results in elevated androgens

Question 4

Presentation of congenital adrenal hyperplasia

Answer 4

Salt wasting (complete inactivity)
Irregular genitals
Irregular periods

Question 5

What do activating mutations in the human FSHR gene cause

Answer 5

Male - normal spermatogenesis despite undetectable gonadotrophins

Question 6

What do inactivating mutations in the human FSHR gene cause

Answer 6

Various presentations -

impairment of spermatogenesis but not azoospermic.

Mild - normal development, infertile responsive to FSH rx

Severe - hypogonadotrophic, infertile and unresponsive to FSH rx

Question 7

What do a single polymorphism do to the FSHR gene

Answer 7

Reduced sensitivty to FSH

Question 8

What do activating LHCGR (LH receptors) mutations look like

Answer 8

Males - premature activation of leydig cell and therefore testosterone, leading to precocious puberty

Females - no obvious phenotype

Question 9

What do patrial inactivating LHCGR (LH receptors) mutations look like

Answer 9

Micropenis - Because lack of LH drive to leydig cells so lack of testosterone

Question 10

What do complete inactivating LHCGR (LH receptors) mutations look like

Answer 10

Complete lack of masculinisation

Question 11

What do LHCGR mutations look like in females

Answer 11

Normal puberty (FSH more important than LH)
Amenhorrhea
Decreased bone mass
No corpus luteum as rely on LH therefore infertility

Question 12

What do LHCGR polymorphisms look like in females

Answer 12

No obvious pheontype

Question 13

How did LuR KO mice present

Answer 13

Males - lack of leydig cells as relys on LH so arrested spermatogenesis

Females - folicular maturation up until pre-ovulatory stage and they never ovulate as LH required for final maturation before ovulation.

Question 14

How do male mice present with overexpressed FSH

Answer 14

Normal size testes and spermatogenesis, infertility and elevated testosterone

Question 15

How do male mice present with under expressed FSH

Answer 15

Small testes
Normal fertility
Decreased sertoli cells
Leydig is normal
No change in serum testosterone
Reduced sperm number and motility

Question 16

How do male mice present with overexpressed LH

Answer 16

Small testes
Infertility
Reduced testosterone

Question 17

How do female mice present with overexpressed FSH

Answer 17

Infertility
Cystic ovaries
Elevated estradiol and progesterone
Bladder obstruction

Question 18

How do female mice present with underexpressed FSH

Answer 18

Infertility
Small ovaries
Suppressed aromatase

Question 19

How do female mice present with underexpressed LH

Answer 19

Small ovaries
reduced progesterone and oestrogen
No corpus luteum

Question 20

What is DSD

Answer 20

Disorders of sexual differentation

Question 21

How is DSD treated

Answer 21

Endocrine manipulation

Question 22

Who does androgen insensitivity syndrome affect

WIDER READING - Hughes 2006

Answer 22

Mild spermatogenic defect or reduced terminal hair to full female features with XY chromosomes

Question 23

What are the three stages of androgen insensitivity syndrome

wider reading - zuccarelo 2008

Answer 23

Determined by the degree of genital masculinity -

CAIS - typically female genitalia
PAIS - typically mixed
MAIS - typically male

Question 24

Is androgen insensitivity syndrome genetic

WIDER READING - Hughes 2006

Answer 24

Usually x-linked recessive and as men only have 1 X then they are going to show.

Question 25

What was one patients cause of their androgen insensitivity syndrome

WIDER READING - Adachi 2000

Answer 25

Believed to be a deficiency in a coactivator protein which interacted with activation function 1 of the androgen receptor.

Question 26

How can the area of mutation help determine what the underlying cause of the androgen insensitivity is

WIDER READING - Yong 2003

Answer 26

mutations in the steroid binding domain have been known to affect androgen binding affinity or retention, mutations in the hinge region have been known to affect nuclear translocation, mutations in the DNA-binding domain have been known to affect dimerization and binding to target DNA, and mutations in the transactivation domain have been known to affect target gene transcription regulation.

Question 27

What is deficient in congenital adrenal hyperplasia and what effect does this have on steroidogenesis

wider reading - Martinez-Arguelles 2018

Answer 27

17-alpha-hydroxylase deficiency, its role is to convert pregnenolone and progesterone to their active forms.

Question 28

How do males and females present with congenital adrenal hyperplasia

WIDER READING - Uwaifo 2018

Answer 28

Results in reduction in fetal testosterone

Delayed puberty in females

Both - hypertension, low potassium.

Question 29

What is linked with the mesonephric duct

Answer 29

Males - antimilarian hormone inhibits paramesonephric duct and testosterone support mesonephric duct

Question 30

What is linked with the paramesonephric duct

Answer 30

Females - No AMH so paramesonephric duct develops and no Sertoli cells so no testosterone so no mesonephric duct