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

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Flashcards in "Medical Physiology Male Reproductive Endocrinology Brian Howell" 4/6 Deck (27):
1

What is TDF?

Testes determining factor
encoded ny SRY gene on Y chromosome

2

In what kind of male are normal testes never produced?

XX male, where SRY gene jumped to C chromosome
Infertility

3

Androgens produced by the Leydig cells promote:

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

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

4

In males, the mesonephros becomes:

the epididymis

5

The Wolffian duct becomes:

the ductus deferens, seminal vesicles and ejaculatory duct

6

In females, the mullerian ducts become:

uterine tube, uterus, cervix

7

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

suppression of LH and FSH

8

Increase in Leydig cells is dependent on:

Maternal HCG in early development, embryonic LH in late development

9

What happens at male puberty?

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)

10

Draw out the HP-testicular axis

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

11

What is the effect of FSH on Sertoli cells?

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

12

What is the fx of estradiol in male stuff?

Damps down activity of Leydig cells

13

What is the function of beta-endorphin?

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

14

What is Kallman syndrome?

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

15

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

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

16

How is estradiol made?

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

17

What enzyme converts T to DHT?

5-alpha-reductase
Rxn mostly occurs in peripheral tissues

18

What is male pseudohermaphroditism?

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)

19

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

DHT levels reduced, T levels okay
Failure of DHT-developement, ie external genitalia or prostate

20

Why do men have higher HCT levels than women?

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

21

How is T bound?

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

22

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

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

23

Why does anabolic steroid abuse cause reduced sperm count?

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.

24

What nervous input maintains detumescence?

Sympathetic from T11-L2
Sympathetic also responsible for ejaculation and emission

25

What nervous input is responsible for tumescence?

PS from S2-S4
Also a little involved in ejaculation

26

Somatic fibers to the penis travel via:

pudendal nerves to striated muscles of the penis
Also contributes to erection

27

Why do DM patients have ED?

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