Rei Chapter 1: Sexual Differentiation From Gonads To Phallus

Front 1

Formation of the TESTIS occurs in the presence of which chromosome?

Back 1

Y chromosome

Hint 1

46 XY

Front 2

Formation of the OVARY occurs in the absence of which chromosome? And presence of which chromosome?

Back 2

Absence of Y and presence of X

Hint 2

46, XY

Front 3

At what gestational age do GONADS begin developing?

Back 3

5-6 weeks

Front 4

Which gene is involved in testis determination?

Where is it located?

Back 4

SRY gene

Located on short arm (p) of Y chromosome

Front 5

What is required for normal ovarian development?

Back 5

A second X chromosome

Front 6

What structures do the Wolffian ducts develop into?

Back 6

Epididymis
Vas Deferens
Seminal vesicles
(Internal genitalia)

Hint 6

Develop IPSI-laterally, dependent on presence/absence of local hormone synthesis

Front 7

What hormone are the Wolffian ducts dependent on?

Back 7

Testosterone

Front 8

What structures do the Müllerian ducts develop into?

Back 8

Fallopian tubes
Uterus
Upper vagina
(Internal genitalia)

Front 9

What structures do the Müllerian ducts develop into?

Back 9

Fallopian tubes
Uterus
Upper vagina
(Internal genitalia)

Hint 9

Develop IPSI-laterally dependent on local hormone presence/absence.

Front 10

What hormone are the Müllerian ducts dependent on?

Back 10

Antimüllerian hormone - in the ABSENCE if AMH, the Müllerian ducts proliferate

Front 11

Where is AMH produced?

Back 11

Sertoli cells

Front 12

Which hormone is crucial in the formation of EXTERNAL genitalia?

Back 12

DHT

(dihydrotestosterone)

+DHT --> male

(-)DHT --> female

Front 13

When does DHT start to be produced?

Back 13

7-8 weeks

Front 14

hCH stimulates which cells to produce more testosterone in males?

Back 14

Leydig cells

Front 15

When is feminization of the external genitalia complete?

Back 15

14 weeks

Front 16

When is masculinization of the external genitalia complete?

Back 16

16 weeks

Front 17

What hormones/receptors mediate decent of the testes?

Back 17

Testosterone

Insuline-like Ligand 3

I-like Ligand 3 Receptor: Lgr3

Front 18

What are the 3 facets of Sexual Differentiation?

Back 18

1.) Gonadal Differentiation

2.) Genital Differentiation

3.) Behavioral Differentiation

Front 19

At what age is sexual/gender identity established?

Back 19

2.5 years old

Front 20

What are the 4 types of etiology for 46, XX Maculinized Female?

Back 20

1. Congenital Adrenal Hyperplasia

2. Maternal androgen excess

3. 46,XX gonadal dysgenesis

4. 46,XX true hermaphroditism

Front 21

What are the 3 types CAH?

Back 21

21-hydroxylase (CYP21) deficiency (90%)

11 B-hydroxylase (CYP11B1) (5%)

3 B-hydroxysteroid dehydrogenase (BHSDII) (least common)

Front 22

Which form of CAH is the salt-losing form?

Back 22

21-hydroxylase deficiency

- Due to low aldosterone secretion

- MCC endocrine neo death

- Autosomal recessive

- Chromosome 6p

Front 23

Which form of CAH is the hypertensive form?

Back 23

11 B-hydroxylase deficiency

- Due to XS corticosterone and 11-deoxycorticosterone

Front 24

Describe the Cortisol pathway...

Back 24

Front 25

Describe the mechanism of abnormal sexual differentiation with CAH

Back 25

Increased cortisol --> high ACTH

--> adrenal androgens --> virilization of external genitalia )fusion of labioscrotal folds, clitoral enlargement)

normal ovaries and Mullerian ducts

Front 26

Clinical manifestations of untreated CAH

Back 26

- Pubic hair by age 2-4 then axillary->body->facial hair

- Premature epiphyseal closure

- Male habitus

- Acne, deep voice, primary amenorrhea, infertility.

Front 27

What are the causes of Maternal Androgen Excess?

Back 27

1.) Maternal ingestion of synthetic androgens - placenta can't aromatize synthetics into estrogens

2.) Neoplasia causing T - placenta can aromatize T, thus protecting F fetus from masculinization

3.) Luteoma - makes DHT, placenta cannot aromatize DHT, so baby gets masculinized.

Hint 27

Treatment is surgical correction of external genitalia abnormalities.

Front 28

Possess an "ovotestis" - testicular tubules and ovarian follicles (separately or together)

Back 28

True Hermaphroditism

46,XX

Front 29

What is the most common karyotype for True Hermaphroditism?

Back 29

46,XX

Front 30

This syndrome is assoc. w/ sensorineural deafness, pt. presents as female but fails to achieve female puberty.

Elev. gonadotropins and streak gonads = to 46,XO but lacks the congenital malformations

Back 30

Gonadal Dysgenesis

(Perrault Syndrome)

46,XX

Front 31

What are the 7 types of etiology for 46, XX Undermasculinized Male?

Back 31

1. Complete/partial gonadal dysgenesis

2. Androgen insensitivity syndrome (complete&partial)

3. 5alpha-reductase deficiency

4. Leydig cell hypoplaisa (Sertoli cell only syndr)

5. Abnormalities of Leydig cell function

6. Isolated persistence of mullerian ducts

Front 32

What factors are involved in gonadal dysgenesis?

Back 32

SRY, SF-1, SOX-9, DMRT1/DMRT2, DAX-1, WNT4

Mutation of these factors can block the differentiation of the bipotent gonad into testis.

Hint 32

This can result in either complete or partial gonadal dysgenesis

Front 33

What is Swyer Syndrome?

Back 33

Complete gonadal dysgenesis

(SRY Deletion)

Front 34

What other disease can gonadal dysgenesis be confused with? Why?

Back 34

Leydig cell hypoplasia

In Swyer syndrome they have a +cervix and uterus, +mullerian system.

Hint 34

Always check that they have a cervix&ut, b/c they could present similarly but actually be Leydig cell hypoplasia, and be missing cervix&ut

Front 35

Describe what you see with Complete gonadal dysgenesis

Back 35

No T, so female external genitalia.

Persistence of mullerian ducts due to Sertoli cell AMH.

Front 36

Describe what you see with Partial gonadal dysgenesis

Back 36

Partial masculinization of external genitalia, partial development of wolffian ducts cut to diminished testicular androgens and AMH.