Lecture 8 Flashcards
What are the 5 patterns of abnormal sexual development we must learn?
- 5-alpha reductase deficiency
- (Complete) Androgen Insensitivity Syndrome
- Congenital Adrenal Hyperplasia
- Klinefelter Syndrome (XXY men)
- XYY men
5-alpha reductase deficiency
5-alpha reductase converts testosterone (T) to dihydrotesoterone (DHT)
DHT more potent than T DURING development - it is responsible for male external genitalia
Leads to female morphology until puberty, followed by conversion to male at puberty
Raised female, but often develop male behavioral traits
What pattenr of heritability does 5-alpha reductase deficiency show?
It is autosomal recessive
Men only
What does it look like
Female genitals until puberty
Male after
5-alpha reductase deficiency (Treatment)
TREATMENT
-DHT topical cream to enlarge genitals in childhood
-Gender based on physiological sex to reduce difficult transition at puberty
(Raise as men)
-Not infertile, all physiological capabilities of typically developing man
Complete Androgen Insensitivity Syndrome
XY with female development
- Women never get it (2Xs)
- Gene for the androgen receptor is on the X chromosome
- We are only interested in complete although partial does exist
Action of the androgen on a target cell (with functional receptors)
Binds to receptor Influences genes These create proteins which influence: Voice Behavior Sperm production Sex differentiation Muscle and bone development Growth
Effects of knocking out the androgen receptor
NO development of the Wolffian system (test) so no internal male organs
No DHT signaling so no external genitalia
Testes also produce anti Mullerian hormone which DOES still work (So no female INTERNAL sex organs
Study on CAIS
Shows what affect at birth?
Wisniewski et al (2000) :
Looked at 14 women with confirmed CAIS
Physical measurements at birth:
CAIS babies no different from unaffected infants in terms of birth weight
External genitalia was completely female with no abnormalities
Essentially the same at birth as XX women
CAIS at puberty
What do you see?
Pubertal feminization still occurs because:
- CAIS DO respond to estrogen
- The testis are a source of androgen, converted to estrogen
- Normal female secondary sex characteristics
Physical indicators of CAIS in adolescence:
- Amenorrhea
- No virilization despite high circulating testosterone
- Absence of post-pubertal axillary hair as there are no receptors for DHEA and Androsenedione
Treatment of CAIS
Best practice is removal of testes after puberty, and feminization by:
Surgical creation of full vagina (in which dilation will still be necessary after surgery to
Vaginal dilation - prevent scarring and vaginal stricture
- Can be painful and distressing, length is the priority, then width
- Dilation is recommended before surgical creation
Typically these omen are infertile as they lack internal sexual organs
Congenital Adrenal Hyperplasia is characterized by
Excess androgens
Types of CAH (2)
Affects males and females
Classic = from conception, Non-classic = late onset
Females and CAH symptoms
FEMALES:
Classic: ambiguous genitalia because high androgens in utero
Non-classic: early pubic hair (hirtruism) (in childhood),
and possibly polycystic ovarian syndrome as the estradiol made by converting androgens to causes follicular development but not evolution (and so forms cysts eventually)
Males and CAH symptoms
MALES:
Often no signs of CAH at birth, possibly hyperpigmentation and penile enlargement
Age of diagnosis of males varies based on severity of aldosterone deficiency
Aldosterone: critical for controlling concentrations of salts
If there is very low aldosterone = salt-wasting disease: hyponatremia and hypovolemia and so this will be picked up earlier medically
No salt-wasting disease present later: virilization and hirtruism before the appropriate age
CAH inheritance/prevelance
Autosomal recessive
1%
What happens in CAH
The pituitary gland regulates the production of hormones in the adrenal glands
Two main parts of the adrenal glands:
Adrenal Medulla
Adrenal Cortex
The adrenal cortex is the part of the adrenal glands affected in CAH
Normally it produces 3 types of hormones:
Cortisol
Physical and emotional stress
Maintains adequate energy supply and blood sugar levels
Aldosterone
Maintains normal levels of sodium and potassium
Maintains normal blood volume of the body
Androgens
DHEA and Androstenedione
BUT in CAH
Deficiency of the enzyme 21-hydroxylase (21-OHD) in the adrenal cortex necessary for the production of cortisol and aldosterone
Non-classical CAH: commence from early childhood to early adulthood
Gradually lose ability to make 21-OHD
As a consequence the only thing the adrenal gland can successfully make is adrenal androgens
