Endocrine Signalling 5 Flashcards
What is androgen insensitivity syndrome
A disorder of sex development involving hormonal resistance due to androgen receptor dysfunction.
What is kleinfelters syndrome and its presentation
XXY - produce less testosterone
Tall, infertile males, small testes and speech disabilities, impaired erectile function, mood disturbances
What causes congenital adrenal hyperplasia
Autosomal recessive disorders -
enzyme deficiencies for adrenal steroid hormones (21-hydroxylase deficiency in 95%) this results in elevated androgens
Presentation of congenital adrenal hyperplasia
Salt wasting (complete inactivity)
Irregular genitals
Irregular periods
What do activating mutations in the human FSHR gene cause
Male - normal spermatogenesis despite undetectable gonadotrophins
What do inactivating mutations in the human FSHR gene cause
Various presentations -
impairment of spermatogenesis but not azoospermic.
Mild - normal development, infertile responsive to FSH rx
Severe - hypogonadotrophic, infertile and unresponsive to FSH rx
What do a single polymorphism do to the FSHR gene
Reduced sensitivty to FSH
What do activating LHCGR (LH receptors) mutations look like
Males - premature activation of leydig cell and therefore testosterone, leading to precocious puberty
Females - no obvious phenotype
What do patrial inactivating LHCGR (LH receptors) mutations look like
Micropenis - Because lack of LH drive to leydig cells so lack of testosterone
What do complete inactivating LHCGR (LH receptors) mutations look like
Complete lack of masculinisation
What do LHCGR mutations look like in females
Normal puberty (FSH more important than LH)
Amenhorrhea
Decreased bone mass
No corpus luteum as rely on LH therefore infertility
What do LHCGR polymorphisms look like in females
No obvious pheontype
How did LuR KO mice present
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.
How do male mice present with overexpressed FSH
Normal size testes and spermatogenesis, infertility and elevated testosterone
How do male mice present with under expressed FSH
Small testes
Normal fertility
Decreased sertoli cells
Leydig is normal
No change in serum testosterone
Reduced sperm number and motility
How do male mice present with overexpressed LH
Small testes
Infertility
Reduced testosterone
How do female mice present with overexpressed FSH
Infertility
Cystic ovaries
Elevated estradiol and progesterone
Bladder obstruction
How do female mice present with underexpressed FSH
Infertility
Small ovaries
Suppressed aromatase
How do female mice present with underexpressed LH
Small ovaries
reduced progesterone and oestrogen
No corpus luteum
What is DSD
Disorders of sexual differentation
How is DSD treated
Endocrine manipulation
Who does androgen insensitivity syndrome affect
WIDER READING - Hughes 2006
Mild spermatogenic defect or reduced terminal hair to full female features with XY chromosomes
What are the three stages of androgen insensitivity syndrome
wider reading - zuccarelo 2008
Determined by the degree of genital masculinity -
CAIS - typically female genitalia
PAIS - typically mixed
MAIS - typically male
Is androgen insensitivity syndrome genetic
WIDER READING - Hughes 2006
Usually x-linked recessive and as men only have 1 X then they are going to show.
What was one patients cause of their androgen insensitivity syndrome
WIDER READING - Adachi 2000
Believed to be a deficiency in a coactivator protein which interacted with activation function 1 of the androgen receptor.
How can the area of mutation help determine what the underlying cause of the androgen insensitivity is
WIDER READING - Yong 2003
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.
What is deficient in congenital adrenal hyperplasia and what effect does this have on steroidogenesis
wider reading - Martinez-Arguelles 2018
17-alpha-hydroxylase deficiency, its role is to convert pregnenolone and progesterone to their active forms.
How do males and females present with congenital adrenal hyperplasia
WIDER READING - Uwaifo 2018
Results in reduction in fetal testosterone
Delayed puberty in females
Both - hypertension, low potassium.
What is linked with the mesonephric duct
Males - antimilarian hormone inhibits paramesonephric duct and testosterone support mesonephric duct
What is linked with the paramesonephric duct
Females - No AMH so paramesonephric duct develops and no Sertoli cells so no testosterone so no mesonephric duct
