Gonadal Differentiation

Question 1

What technique was used in mapping out sex chromosomes?

Answer 1

FISH

Question 2

What is SRY protein?

Answer 2

Sex-determining region Y, DNA-binding protein that initiates testes development

Question 3

What is SF-1?

Answer 3

Steroidigenic factor-1, transcription factor that is important for gonadal and adrenal development, reproduction, and production of anti mullerian hormone

Question 4

What do mutations in SF-1 lead to?

Answer 4

A range of problems including adrenal insufficiency in 46,XY females (low androgens), and gonadal dysgenesis

Question 5

What does translocation of SRY lead to?

Answer 5

46,XX males (SRY functional)

Question 6

What does mutation of SRY lead to?

Answer 6

Mutation of SRY leads to 46,XY females (loss of SRY function)

Question 7

What does the presence of androgens induce in males?

Answer 7

Prenatally induces genital differentiation, during puberty induces the development of secondary sex characteristics

Question 8

What does the low amount of androgens allow for in females?

Answer 8

Female genital differentiation and the development of female secondary sex characteristics

Question 9

What does it mean that the undifferentiated gonad is bipotential?

Answer 9

Has the potential to form testes or ovaries

Question 10

What are mullerian ducts?

Answer 10

Paired ducts of the embryo that run down the lateral sides of the urogenital ridge. Formed due to levels of estrogen, not exposed to AMH or androgens

Question 11

What do mullerian ducts form in females vs males?

Answer 11

In females, they will form the fallopian tubes, uterus, and the upper portion of the vagina. In males, they are lost

Question 12

What is the default form of the gonad?

Answer 12

Female, without exposure or sensitivity to androgens, the gonad becomes a female gonad

Question 13

What is the wolffian duct?

Answer 13

Paired organ also found during embryogenesis. In males it develops into the epididymis, vas deferens, and the seminal vesicle. They must be exposed to testosterone during embryogenesis

Question 14

What is anti-mullerian hormone?

Answer 14

It is a member of the TGF-B family produced by sertoli cells and leydig cells to stabilize wolffian ducts

Question 15

Does testicular differentiation or ovarian differentiation come first?

Answer 15

Testicular differentiation precedes ovarian development

Question 16

What is amenorrhea?

Answer 16

Lack of menstrual cycle after age 16 or 3 missed periods. Possible sign of genetic, endocrine, or anatomic abnormalities –> GnRH deficiency, functional hypothalamic amenorrhea, hyperprolinactinemia.

Question 17

What is Kallmann’s syndrome?

Answer 17

Adhesion molecule genetic mutation - no migration of gnRH producing cells to hypothalamus –> no sexual maturity –> don’t get correct location of release

Question 18

What is functional hypothalamic amenorrhea?

Answer 18

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

Question 19

What is hyperprolactinemia?

Answer 19

Dopamine is not inhibiting prolactin release

Question 20

What is menopause?

Answer 20

Ovary ceases to function at age 51 –> hot flashes, urogenital atrophy, osteoporosis, cardiovascular disease, many psychological issues

Question 21

What is Klinefelter’s syndrome?

Answer 21

Male, XXY –> more than one X chromosome. Causes gonadal dysgenesis, low testosterone, sometimes no clear secondary sex characteristics. Occurs in 1/500 males. It is the most common form of male hypogonadism –> low androgens

Question 22

What is Turner’s Syndrome?

Answer 22

Missing X chromosome. Gonadal dysgenesis, almost no estrogen or progesterone, no secondary sex characteristics, short stature, webbed neck, heading loss. Most often the father did not pass on sex chromosomes. Treatable with hormones.

Question 23

What is intersex 46,XY?

Answer 23

Have testes, but genital ducts or external genitalia are not fully masculinized. May be caused by defect in testosterone secretion or androgen insensitivity syndrome.

Question 24

What are defects in testosterone secretion?

Answer 24

May have SF-1 mutation or LHR mutation –> not a receptor problem. May lead to testicular dysgenesis, impaired T or AMH secretion, gonadal tissue not responsive, no T –> DHT conversion (may lack 5alpha reductase) –> DHT important for secondary sex characteristics

Question 25

What is androgen insensitivity syndrome?

Answer 25

Complete –> 46, XY
Have testes present, but absent wolffian ducts, female appearing external genitalia. Female secondary sex characteristics, no menarche. Increased LH secretion –> increased T and E2 –> problem with receptor of testosterone

Incomplete –> variable presentation

Question 26

What are possible contributors to androgen biosynthetic dysfunction in 46, XY individuals?

Answer 26

LH receptor mutation (dec androgen production), 17a-hydroxylase deficiency (cant make androgens), 5a-reductase deficiency (cant make DHT)