Phys DSA (montemayor) - SRS

Question 1

What is another name for klinefelter syndrome?

Answer 1

•XXY Seminiferous Tubule Dysgenesis

Question 2

What promotes the intrauterine development of the testes?

Answer 2

SRY gene produces TDF (testes determining factor)

Question 3

What cells produce antimullerian hormone?

Answer 3

Sertoli cells

Question 4

What hormone action is needed for the wolfian duct to develop?

Answer 4

Testosterone

Question 5

What are the wolfian duct structures?

Answer 5

seminal vesicles

ejaculatory duct

vas deferens

epididymus

Question 6

Which cells in the testes produce testosterone?

Answer 6

Leydig cells

Question 7

What hormone stimulates fetal leydig cell production of testosterone during development prior to fetal pit. LH?

Answer 7

HCG

Question 8

•What is required for the development of the penis, scrotum and prostate?

Answer 8

–DHT (Dihydrotestosterone)

Question 9

•What enzyme is required for the conversion of testosterone à DHT?

Answer 9

–5α-reductase-2

Question 10

–5α-reductase-1 is more expressed in skin, so in what condition might this come into play?

Answer 10

Acne treatment

Question 11

Which binds tighter to their shared receptor, DHT or testosterone?

Answer 11

DHT

Question 12

5α-reductase-2 deficiencies lead to what phenotypical changes?

Answer 12

ambiguous or feminized external genitalia

Question 13

What goes down at 6-8 weeks gestation in the male differentiation

Answer 13

Differentiation of testes

[SRY transcription factor]

Question 14

What happens in weeks 8-9 of male gestational development (UG tract)

Answer 14

• Retention of wolffian ducts
  
  • [Testosterone]
• Regression of müllerian ducts
  
  • [Antimϋllerian hormone]

Question 15

What happens in weeks 9-13 of male genital development?

Answer 15

Male-type external genitalia

[DHT]

Question 16

In klinefelters, why the gynecomastia?

Answer 16

–Elevated estradiol levels and increased estradiol-to-testosterone ratio

–Peripheral conversion of testosterone à estradiol

Question 17

•Which enzyme converts androgen to estrogen?

Answer 17

–CYP19-aromatase

Question 18

•What hormone is considered to be responsible for the normal initiation of puberty?

Answer 18

–Resurgence of pulsatile sleep-associated GnRH secretion from the hypothalamus during adolescence, along with increased gonadotrope sensitivity to GnRH.

Question 19

In this patient with Klinefelter Syndrome, increased levels of gonadotropins failed to induce normal testicular growth and spermatogenesis.

What happpens to the testes?

Seminiferous tubules?

Answer 19

• The testis became fibrotic and hyalinized and remain small and firm.
• The seminiferous tubules are largely destroyed and he is infertile.

Question 20

What hormones are affected and how in primary hypogonadism?

Answer 20

–Gonadotropin levels are elevated

–Androgen production is reduced

Question 21

What hormone is the key player in development of secondary sex characteristics, such as penis size, bear development, etc?

Answer 21

DHT

Question 22

What percent of testosterone circulates as….

–SHBG (sex hormone-binding globulin) bound:

–Serum albumin bound:

–Free:

Answer 22

–SHBG (sex hormone-binding globulin) bound: 45-60%

–Serum albumin bound: 38-55%

–Free: 2-5%

Question 23

•Which cells are the primary site for the production of testosterone in males?

Answer 23

LEydig cells

Question 24

•What protein is responsible for maintaining testosterone concentration in the testes?

Answer 24

–ABP (androgen-binding protein)

Question 25

•Why is it important for testosterone to be concentrated within the testes?

Answer 25

–Maintenance of adequate concentration [~ 100x > circulating levels] within the testes is essential for the promotion of adequate spermatogenesis.

Question 26

From cholesterol to testosterone, elaborate the intermediates in the production pathway.

Answer 26

1. Cholesterol
2. pregnenolone
3. progesterone
4. androstenedione
5. testosterone

Question 27

Maintenance of adequate concentration [~ 100x > circulating levels] within the testes is essential for the promotion of adequate spermatogenesis. Describe how this is accomplished.

Answer 27

Androgen binding protien (ABP) in the seminiferous tubules binds testosterone with high affinity.

Question 28

What is testosterone converted to in peripheral tissues and by what?

Answer 28

Estradiol (CYP19-aromatase)

DHT (5α-reductase-2)

Question 29

•What promotes LH and FSH secretion?

Answer 29

–Pulsatile hypothalamic GnRH release stimulates anterior pituitary LH and FSH secretion

Question 30

•Which cells are the target of LH in the testes?

Answer 30

–Leydig cells

Question 31

•Which cells are the target of FSH in the testes?

Answer 31

–Sertoli cells

Question 32

Sertoli cells have a number of functions, what general actions do these functions fall undeR?

Answer 32

Supportive function

Exocrine function

Endocrine function

Question 33

What are the supportive functions of the sertoli cells?

Answer 33

• Maintaining blood-testis barrier

• Phagocytosis
• Transfer of nutrients to sperm

• Receptors for hormones & paracrines

Question 34

What are the exocrine functions of the sertoli cells?

Answer 34

• Fluid produced for sperm mobilization
• Production of ABP (Androgen binding protein)
• Spermination: release of sperm from seminiferous tubule

Question 35

What are the endocrine functions of the sertoli cells?

Answer 35

• Expression of testosterone, ABP and FSH receptors
• Production of AMH (Antimϋllerian hormone)
• CYP19 Aromatase: testosterone à estradiol-17β (local)
• Production of inhibin B to regulate FSH levels

Question 36

In klinefelter, you will see low serum testosterone levels and elevated gonadotropin levels (LH and FSH). What is the explanation for elevated LH and FSH levels?

Answer 36

–Reduction in androgen production results in decreased negative feedback on the hypothalamic-pituitary-testicular axis

Question 37

What does inhibin provide negative feedback on in men?

Answer 37

FSH

Question 38

•Which 3 key hormones have an important function to promote adequate spermatogenesis in the normal male?

Answer 38

–Testosterone from Leydig cells

–FSH & LH (necessary for Leydig and Sertoli function)

Question 39

How does FSH contribute to spermatogenesis?

Answer 39

stimulates the Sertoli cells (nursing cells) to nurse and form sperm

Question 40

Does estradiol have a role in spermatogenesis?

Answer 40

Yes, unclear what though

Question 41

What role does GH have in development of sperm?

Answer 41

•. GH promotes early division of the sperm. Without it, as seen in pituitary dwarfs, spermatogenesis is severely deficient or absent resulting in infertility.

Question 42

•What treatment might be suggested for this patient with Klinefelter Syndrome?

Answer 42

–Androgen replacement therapy

Question 43

•What would be the likely effect of administering exogenous testosterone to a klinefelter patient?

Can exogenous testosterone promote fertility in these patients? explain your answer.

Answer 43

–Virilization of secondary male sexual traits

–No

–Seminiferous tubule tissue is likely destroyed and the cause of infertility

Also, in more detail…

–Exogenous testosterone (T, DHT, and estradiol-17β) promotes negative feedback on gonadotropin secretion

–↓ LH –> further ↓ T production by Leydig cells –> ↓ testicular [T] –> ↓ spermatogenesis

Question 44

What impact does defective steroidogenesis have on spermatogenesis?

Answer 44

•Normal spermatogenesis almost never occurs when steroidogenesis is defective

May still have defective spermatogenesis though

Question 45

In klinefelters why does a female phenotype fail to develop despite the presence of multiple X chromosomes?

Answer 45

–Antimϋllerian hormone –> Mϋllerian duct regression