"Medical Physiology Male Reproductive Endocrinology Brian Howell" 4/6

Question 1

What is TDF?

Answer 1

Testes determining factor

encoded ny SRY gene on Y chromosome

Question 2

In what kind of male are normal testes never produced?

Answer 2

XX male, where SRY gene jumped to C chromosome

Infertility

Question 3

Androgens produced by the Leydig cells promote:

Answer 3

1. differentiation of Wolffian ducts - requires testosterone
2. Prostate development - requires DHT

Anti-mullerian hormone from Sertoli cells causes mullerian ducts to degenerate

Question 4

In males, the mesonephros becomes:

Answer 4

the epididymis

Question 5

The Wolffian duct becomes:

Answer 5

the ductus deferens, seminal vesicles and ejaculatory duct

Question 6

In females, the mullerian ducts become:

Answer 6

uterine tube, uterus, cervix

Question 7

Constant levels as opposed to pulsatile, of GnRH, result in:

Answer 7

suppression of LH and FSH

Question 8

Increase in Leydig cells is dependent on:

Answer 8

Maternal HCG in early development, embryonic LH in late development

Question 9

What happens at male puberty?

Answer 9

Frequency and amplitude of GnRH pulses increase
Sensitivity of HP axis to testosterone decreases
Gonadotroph sensitivity to GnRH increases
LH and FSH production increase
Spermatogenesis begins
Androgen changes occur (secondary sex characteristics)

Question 10

Draw out the HP-testicular axis

Answer 10

Hypothalamus makes GnRH
GnRH acts on AP to produce LH and FSH
FSH acts on Sertoli cells to produce inhibin (and growth factors, proteins etc.)
Inhibin negatively feeds back to AP
LH acts on Leydig cells to produce testosterone
Testosterone has a positive paracrine effect on Sertoli cells
Testosterone negatively feeds back to AP and Hypo

Question 11

What is the effect of FSH on Sertoli cells?

Answer 11

1. ABP - keeps T in testes
2. P450 aromatase - makes estrogen
3. inhibins - feedback, suppress Leydig cell proliferation
4. Growth factors for sperm production - ie increase LH receptors on Leydig cells

Question 12

What is the fx of estradiol in male stuff?

Answer 12

Damps down activity of Leydig cells

Question 13

What is the function of beta-endorphin?

Answer 13

Beta-endorphin, made by Leydig cells - inhibit Sertoli cell proliferation

Question 14

What is Kallman syndrome?

Answer 14

Hypogonadotropic hypogonadism
No LH or FSH
Congenital anosmia
Pts fail to enter puberty
Mutations in KAL-1X, FGFR1, PROK2, PROKR2, failure of GnRH cells to migrate into the hypothalamus
Long-term consequence is osteoporosis

Question 15

Desmolase, aka P450 side chain cleavage enzyme, does what?

Answer 15

Converts cholesterol to pregnenolone, step up-regulated by LH***
Rxn in mitochondria

Question 16

How is estradiol made?

Answer 16

Adrostenedione via aromatase –> estrone –> estradiol
Or
Testosterone via aromatase –> estradiol
Happens in Sertoli cells

Question 17

What enzyme converts T to DHT?

Answer 17

5-alpha-reductase

Rxn mostly occurs in peripheral tissues

Question 18

What is male pseudohermaphroditism?

Answer 18

1. 5-alpha-reductase deficiency (1 cause, but anything that interferes with male androgen synthesis causes MPH)
2. Androgen insensitivity syndrome (T and DHT levels okay but no androgen receptors, genitalia develop as women)

Question 19

What are the symptoms of 5-alpha-reductase deficiency?

Answer 19

DHT levels reduced, T levels okay

Failure of DHT-developement, ie external genitalia or prostate

Question 20

Why do men have higher HCT levels than women?

Answer 20

Androgens increase the expression of EPO in the kidneys which leads to higher HCT.

Question 21

How is T bound?

Answer 21

T is bound to albumin and sex-hormone binding golbulin. Only 2% of T is free and that is the active stuff.

Question 22

What is Kennedy’s Disease (aka Spinobulbar Muscular Atrophy)?

Answer 22

Mutation in androgen receptors causes LMN disease
CAG repeat expansion causes polyglutamine expansion in androgen receptor
Toxic gain of fx
Progressive weakness due to degeneration of LMN in brain stem and spinal cord
Presents similarly to ALS but does not affect the diaphragm.
X-linked

Question 23

Why does anabolic steroid abuse cause reduced sperm count?

Answer 23

Extra T feeds back to AP and leads to low levels of FSH and LH. Leads to low T in testes (no LH or ABP) which cannot promote sperm development.

Question 24

What nervous input maintains detumescence?

Answer 24

Sympathetic from T11-L2

Sympathetic also responsible for ejaculation and emission

Question 25

What nervous input is responsible for tumescence?

Answer 25

PS from S2-S4

Also a little involved in ejaculation

Question 26

Somatic fibers to the penis travel via:

Answer 26

pudendal nerves to striated muscles of the penis

Also contributes to erection

Question 27

Why do DM patients have ED?

Answer 27

Vascular disease and autonomic dysfunction mean that input to vascular smooth muscle and endothelium is compromised.