Gonadal Differentiation

Question 1

what is sexual differentiation largely driven by

Answer 1

by the presence (or lack) of androgens

Question 2

what is the genetic “default”

Answer 2

female

Question 3

what does Anti-mullerian hormone (AMH) stabilize

Answer 3

the wolffian ducts

Question 4

what initiates testes development

Answer 4

Sex-determining regions Y (SRY protein)

Question 5

what is steroidogenic factor 1 (SF-1) important for

Answer 5

•important for gonadal and adrenal development, reproduction and Anti-Mullerian Hormone

Question 6

what do mutations in SF-1 lead to

Answer 6

•Mutations in SF-1 lead to a range of problems including adrenal insufficiency in 46, XY females (low androgens), gonadal dysgenesis/dysfunction

Question 7

what does translocation of SRY lead to

Answer 7

46, XX males (SRY functional) but mutation of SRY lead to 46XY females (loss of SRY function)

Question 8

The presence of androgens induces a number of irreversible changes in males - what are they? (2)

Answer 8

Prenatally to induce genital differentiation; during puberty, the development of secondary sex characteristics – the larger facial bones, hand, feet and heights in males

Question 9

in females what does the lower amount of androgen allow for

Answer 9

•for female genital differentiation and the development of female secondary sex characteristics – there are many things that effect these androgen/estrogen ratios

Question 10

what is testicular and ovarian differentiation influenced by

Answer 10

a combination of hormonal and environmental factors

Question 11

what are mullerian ducts

Answer 11

•Mullerian ducts (or paramesonephric ducts) are paired ducts of the embryo that run down the lateral sides of the urogenital ridge

Question 12

what do mullerian ducts develop into in both males and females

Answer 12

In the female they will develop to form the fallopian tubes, uterus and the upper portion of the vagina; in the male they are lost. Without exposure or sensitivity to androgens the default form is female

Question 13

what are wolffian ducts

Answer 13

•The Wolffian duct (or mesonephric duct) is a paired organ also found in humans during embryogenesis

Question 14

what do wolffian ducts develop into in males

Answer 14

In males it develops into the epididymis, the vas deferens and the seminal vesicle
-it is critical that the wolffian ducts are exposed to testosterone during embryogenesis for development

Question 15

What is Anti-mulerian hormone produced by and what does it control

Answer 15

•Anti-Mullerian hormone (or Mullerian Inhibiting Factor – TGF-B family) produced by Steroli cells and Leydig cells control stabilization of Wolffian ducts

Question 16

what precedes ovarian differentiation

Answer 16

testicular differentiation

Question 17

menopause

Answer 17

ovary ceases to function at the average age of 51

Question 18

Amenorrhea

Answer 18

lack of menstrual cycle after age 16 or 3 missed periods possible sign of genetic, endocrine or anatomic abnormalities

Question 19

GnRH deficiency (Kallmann’s Syndrome)

Answer 19

Adhesion molecule gene mutation – no migration of GnRH producing cells or olfactory neurons to the hypothalamus…no sexual maturity of smell

Question 20

Functional hypothalamic amenorrhea

Answer 20

Reduced GnRH pulse frequency and amplitude – low FSH and LH, leptin implicated (low levels), minor activation of HPA axis and incidences of psychological stress, strenuous exercise or poor nutrition precede

Question 21

Hypeprolactinemia

Answer 21

Usually dopamine not inhibiting prolactin release, a common cause (25%)

Question 22

Intersex people

Answer 22

people in the population who identify as the sex opposite or indifferent to their karyotype
•are individuals born with any of several variations in sex characteristics including chromosomes, gonads, sex hormones or genitals that do not fit the typical definitions for male or female bodies

Question 23

what does sex refer to

Answer 23

refers to the biological and physiological characteristics that define men and women

Question 24

what does gender refer to

Answer 24

refers to the socially constructed roles, behaviours, activities and attributes that a given society considers appropriate for men and women

Question 25

Kleinefelter’s Syndrome

male 47, XXY

Answer 25

• Gonadal dysgenesis, low testosterone, sometimes no clear secondary sex characteristics and may be mental disability (but rare)
• 1/500 males and is most common form of male hypogonadism and is also the most commonly found human sex chromosomal abnormality
• low androgens

Question 26

Turner’s Syndrome

female 45,X

Answer 26

• Gonadal dysgenesis, no estrogen or progesterone, no secondary sex characteristics, numerous developmental problems including short, web neck, hearing and kidney loss of function
• Mostly fatal to fetus so only 1/5000
• Most often father did not pass on a sex chromosome

Question 27

are turners syndrome and kleinfelters both treatable

Answer 27

yes with hormones for secondary sex characteristics but will always be infertile

Question 28

male hypogonadism

Answer 28

•Developmental default is female so hypogonadism in males leads to female characteristics

Question 29

Female 46, XXX DSD - intersex (formerly called Pseudohermaphrodism)

• what does it occur from
• _____ hypertrophy
• exposure at earlier stages of development leads to what
• what would genetalia look like

Answer 29

• Prenatal exposure to androgens (1/16,000) – can happen from natural causes or unnatural such as being exposed to drugs in utero
• Exposure after 12th fetal week leads only to clitoral hypertrophy
• Exposure at progressively earlier stages of differentiation leads to retention of the urogenital sinus and labioscrotal fusion
• Both ovarian and testicular tissue in one or both gonads – often ambiguous genitalia

Question 30

Intersex 46, XY DSD (formerly called male pseudohermaphordism)

• what is present / lacking
• defect in secretion of what
• ________ dysgenesis

Answer 30

•1/50,000 – have testes but genital ducts or external genitalia not fully masculinized
•Defect in Testosterone (T) secretion (for example SF-1 mutation or LHR mutation)
-Testicular dysgenesis, impaired T or MIF secretion, gonadal target tissue not responsive, no T DHT conversion (so also may lack 5a-reductase)

Question 31

Androgen Insensitivity syndrome (AIS, resistance)

• what is present/lacking
• what occurs at puberty
• increase of ___ secretion
• which receptor mutated

Answer 31

• 46, XY so present as normal females but don’t have ovaries
• testes present but absent wolffian ducts, female-appearing external genitalia
• at puberty female secondary sex characteristics but no menstruation
• increase of LH secretion leading to increased T and E2 (peripheral and testes)
• androgen receptor mutation is common

Question 32

Luteinizing Hormone (LH) receptor (LHR) mutation – decreased androgen production, hypogonadism, called:

Answer 32

intersex 46, XY DSD

Question 33

17a- hydroxylase deficiency – can’t make androgens so have ambiguous gonads or feminization called:

Answer 33

intersex 46, XY DSD

Question 34

5a-reductase deficiency – can’t make DHT, called:

Answer 34

46, XY DSD

Question 35

21 a-hydroxylase deficiency – build-up of androstenedione and DHEA – increase T, masculinization, called:

Answer 35

intersex 46, XX DSD

Question 36

Aromatase deficiency – lack of estrogen, called:

Answer 36

46, XX DSD

Question 37

Increased androgen exposure in utero (e.g. androgenic drugs), called:

Answer 37

46, XX DSD