Male Reproductive Endocrinology

Question 1

What is required for the development of testes and germ cells to develop into spematogonia?

Answer 1

SRY

Question 2

What is required for the external genitalia to develop?

Answer 2

dihydrotestosterone (DHT)

Question 3

How does XX male occur?

Answer 3

SRY gene translocates to X chromosome during male meiosis—testis determining factor (TDF) is put on males X chromosome–XY Female can occur if TDF is absent from Y chromosome

Question 4

Androgens produced by Leydig cells promote what?

Answer 4

Differentiation of the Wolffian (mesonephric) duct–Requires testosterone—NOT DHT

Prostate development—REQUIRES DHT

Question 5

What causes Mullerian ducts to degenerate?

Answer 5

Anti-Mullerian hormone released from Sertoli cells

Question 6

What do the mesonephros develop into in males?

Answer 6

epididymis

Question 7

What does the Wolffian duct develop into in males?

Answer 7

vas deferens
seminal vesicles
ejaculatory duct

Question 8

What happens to the Mullerian ducts in males and in females?

Answer 8

Degenerate in males

form the fallopian tubes/uterus/cervix in females

Question 9

What does constant release of GnRH cause?

What can this treat?

Answer 9

Prevents LH and FSH release

Downregulation of receptors

Prostate cancer–to lower testosterone production

Question 10

What is the mechanism for GnRH activation?

Answer 10

GCPR –gonadotroph receptor–activates PLC–release Ca–DAG and PKC activation

Question 11

What is the increase in Leydig cells dependent on?

Answer 11

maternal chorionic gonadotropin (hCG)–early development

embryonic LH–late development

Question 12

Prior to puberty how is hormones levels maintained at a low level?

Answer 12

Few GnRH pulses–low FSH and LH levels

Hypothalamus and pituitary–very sensitive to negative feedback inhibition by androgens

Question 13

What occurs at puberty?

Answer 13

Frequency and amplitude of GnRH pulses increase
Sensitivity of H-P axis to negative feedback of testosterone decreases
Gonadotroph sensitivity to GnRH increases
LH and FSH production increases
Testosterone increases and spermatogenesis begins
Androgen-driven changes characteristic of puberty occur

Question 14

What does LH bind to stimulate production of testosterone?

Answer 14

Leydig cells

Question 15

What does FSH bind and what proteins are produced from this binding?

Answer 15

Sertoli cells

ABP/aromatase/growth factor/inhibin

Question 16

What inhibits release of GnRH from the hypothalamus?

Answer 16

testosterone neg feedback

Question 17

What inhibits FSH release from the anterior pituitary?

Answer 17

Inhibin neg feedback

Question 18

Stimulation of Leydig cells with LH occurs how and what does this cause?

Answer 18

GPCR–cAMP–PKA

Increases transcription of

• Enzymes involved in testosterone synthesis
• Stimulates rate-limiting step (cholesterol to pregnenolone) in testosterone synthesis
• Sterol carrier protein and sterol activating protein synthesis

Question 19

Stimulation of Sertoli cells by FSH occurs how and what does this cause?

Answer 19

GPCR–cAMP–PKA

Increases transcription of

• androgen binding protein–keeps testosterone levels high
• P450 aromatase–produces estrogen
• growth factors–support sperm production
• inhibin- suppress Leydig cell proliferation/suppress FSH secretion

Also has secondary effects on Leydig cells and sperm (increases motility)

Question 20

What do Leydig cells produce that act on Sertoli cells?

Answer 20

Testosterone

B-endorphin–which inhibit Steroli cell proliferation

Question 21

What do Sertoli cells convert testosterone to that acts on Leydig cells?

Answer 21

Estradiol

Question 22

What is Kallmann Syndrome?

Answer 22

Mutation causing congenital anosmia (complete inability to smell) and failure to enter puberty—Main danger is osteoporosis

hypogonadotropic hypogonadism–GnRH neurons and olfactory neurons have same developmental origin

Question 23

What is the rate limiting step of testosterone production and where/how does it occur?

Answer 23

Cholesterol—>pregnenolone occurs in the mitochondria through P450 side chain cleavage enzyme–Desmolase–removes side chain of cholesterol

Question 24

What does 5a reductase deficiency cause?

Answer 24

Male Pseudohermaphroditism–DHT levels reduced—failure of development of urogenital sinus and external genitalia

Question 25

What is seen in Androgen insensitivity syndrome?

Answer 25

Normal testosterone and DHT levels
Androgen receptors are absent/defective—urogenital sinus and external genitalia develop according to female pattern—–wolffian ducts degenerate

Question 26

What is Kennedy’s Dz/Spinobulbar Muscular Atrophy and how is it caused?

Answer 26

Lower motor neuron dz caused by mutation in the androgen receptor –toxic gain of function mutation–leading to progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord

Question 27

Does FSH and LH levels increase or decrease with aging?

Answer 27

Increase

Question 28

What does Finasteride do?

Answer 28

Block production of DHT–increasing testosterone levels