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ER Week 4 > Male Reproductive Physiology and Pharmacology > Flashcards

Male Reproductive Physiology and Pharmacology Flashcards

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1
Q

WHere does spermatogenesis happen?

A

in the seminiferous tubules of the testicles

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2
Q

Where in the tubule are the spermatogonia located?

A

closest to the basement membrane - they move further in as they develop with spermatozoa at the very inner portion

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3
Q

SPermatogenesis is staggered throughout the seminiferous tubules sot hat all developmental phases are present at any one time. What is a spermatogenic wave?

A

defined as the time (distace) it takes for the reappearance of the same stage within a given segment of the seminiferous tubule

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4
Q

Why is this important?

A

it ensures that spermatozoa are produced continuously so that mature speram are always available for when the male finds a ready female

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5
Q

Because of spermatogenic waves, drug or environmental conditions that affect spermatogenesis may be measureable for how long?

A

up to 2 months post insult

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6
Q

What is the average daily sperm production?

A

about 100 million

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7
Q

Spermatogenesis is positively correlated with what hormone?

A

testosterone levels

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8
Q

How long does it take for the mitosis stage?

A

16 days

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9
Q

How long doe sit take for the first meiosis?

A

24 days

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10
Q

How long does it take for the second meiosis

A

only a few hours

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11
Q

How long does spermiogenesis take?

A

24 days

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12
Q

What does GnRH trigger in the males

A

anterior pit release of FSH and LH

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13
Q

What does FSH and LH do in the male?

A

make testis produce testosterone

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14
Q

Testosterone has negative feedback at what levels?

A

both hypothalamus and anterior pituitary

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15
Q

What cell does the LH bind to in the male?

A

leydig cell

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16
Q

What does this promote?

A

production of testosterone

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17
Q

What does the FSH bind to in the male?

A

sertoli cells

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18
Q

What does this trigger?

A
  1. makes androgen binding protein to increase concentratin of testosterone
  2. production of inhibin
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19
Q

WHat do the sertoli cells do for the developing sperm?

A
  1. protects them from plasma
  2. nrouishes them
  3. secretes luminal fluid and provides androgen binding protein
  4. secretes paracrine agents that stimulate sperm proliferation and differentiation
  5. make inhibin
  6. paracrine signals to leydigs
  7. phagocytize defective sperm
  8. secrete mullerian inhibitin substance
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20
Q

Low sertoli cells numbers are associated with….

A

low spermatogenesis

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21
Q

Low leydig cell numbers are correlated with what hormone levels?

A

decreased testosterone levels

increased gonadotropin levels (lack of negative feedback)

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22
Q

WHat are some symptoms of decreased testosterone (andropause)?

A

decrease in testicular function
erectile dysfunction
weight gain
gynecomastia

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23
Q

How do we diagnose androgen deficiency?

A

total testosterone level

may follow up with FSH/LH

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24
Q

What are the treatment optoins for androgen deficiency?

A

hormone replacement
sleep, eat, exercise
viagaral for ED

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25
Q

WHat are the thre emain natural androgens?

A

androstenedione
testosterone
dihydrotestosterone

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26
Q

What tissues will be affected by targeting testosterone?

A

muscle
seminal vesicle
epididymis
boen

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27
Q

What tissues will be affected by the 5alpha reductase inhibitors?

A

prostate
external genitalia
skin - hair pattern

28
Q

Where is most of the testosterone in the male produced?

A

95% in leydig cells

5% in adrenals

29
Q

What is the most potent of the natural testosterone?

A

dihydrotestosterone

30
Q

Gemales have 20x less androgen than males, but where are they made?

A

adrenals and ovaries

31
Q

What will bind the androgens and estrogens and 19-nor progestins?

A

sex hormone binding lbogulin

32
Q

Where else is sex hormoen binding globulin made besides sertoli cells?

A

liver

33
Q

The androgen receptor binds all androgens and belongs to what family?

A

steroid receptor superfamily - acts as a transcription factor

34
Q

What will convert testosterone to DHT?

A

5alpha reductase

35
Q

What are the anabolic effects of androgens?

A

muscle building - positive nitrogen balance, increase in protein synthesis

bone growth and closure of epiphysis

sodium and water retention (similar to estrogen)

36
Q

What are the testosterone preparations?

A 
oral
pellets
transdermal patch
gel 
transbuccal
37
Q

What is the main Testosterone analog?

A

methyl testosterone

38
Q

Where is the methyl substitution t make it orally actie?

A

7-17

39
Q

What are the side effects of methyl testosterone?

A

hepatotoxicity

acute cholecytstitic

40
Q

What is the DHT derivatige?

A

oxandrolone

41
Q

Which one is more used for testosterone hormoen replacement and which is the anabolic steroid

A

methyl testosterons it eh HRT

osandrolone is the anabolic steroid

42
Q

What are the adverse effect sof androgen therapy?

A
  1. growth interruption in growing youth (premature bone closure)
  2. priapism
  3. sodium and water retention
  4. jaundice
  5. hepatic carcioma
  6. hypogonadism (long term cessation of HPO axis)
  7. aggressive behavior
  8. urinary obstruction - due to prostate growth
    gynecomastia, testicular shrinkage, baldness
43
Q

Why so many side effects?

A

Studies have shown that androgen-anabolic steroids bind to glucocorticoid, progesterone, and estrogen receptors and exert multiple effects

44
Q

What are the purposes for medical castration?

A

to interfere with precocious puberty

  1. to treat androgen dependent cancers
  2. reduce libido
45
Q

What are the three options for medical castration?

A
  1. androgen receptor antagonists
  2. nonpulsatile GnRH agonists
  3. nonpulsatile GnRH antagonists
46
Q

What is intracrinology?

A

local formation of sex steroids

important in postmenopausal women where all estrogesna nd androgens are made locally in peripheral target tissues

47
Q

Why is intracrinology important in treating disease?

A

if the goal is to shut down the hypothalamic pituitary gonadal axis, the GnRH agonists and antagonists are fine

but if the goal is to reduce androgen receptor signaling in a peripheral tissue like the prostate gland, you need to use an androgen receptor antagonist and/or 5 alpha reductase inhibitor

48
Q

What is cyproterone acetate?

A

androgen antagonist

49
Q

What is cyproterone acetate used for?

A
  1. reduce excessive sexual drive in men

2. trea thirsutism in women with combo of estrogen

50
Q

What are the nonsteroidal pure receptor androgen antagonist?

A

Flutamide, Bicalutamide, Nilutamide

51
Q

What are the flutamides used for?

A

advanced prostate cancer

52
Q

What are the side effect sof the flutamides?

A

gynecomastia, hepatotoxicity

53
Q

What is spinoloactone

A

it’s a weak androgen antagonist

54
Q

What is spironolactone used for?

A

hirsutism and acne in women
diuretic is the main use
in some OCP

55
Q

What is the hu,an recombinant GnRH agonist?

A

gonadorelin

56
Q

What do we use gonadorelin for?

A
  1. used for functional assessment of the gonadal response

2. male infertility - give pulsatile

57
Q

What is the main synthetic GnRH agonist?

A

leuprolide

58
Q

What is leuprolide used for?

A

castration for cancer treatment - continuous sabdministration causes hypersection of LH and FSH first, but then suppression

uterine fibrois

ovarian stimulation with pulsatile administration

also gonadotropin dependent precocious puberty

59
Q

What are the two GnRH antagonists?

A

Degarelix

Ganirelix and Cetrorelix

60
Q

What is the main 5 alpha reductase inhibitor?

A

finasteride

also Dutasteride

61
Q

What is finasteride used for?

A

BPH

male pattern baldness

62
Q

What additional things can dutasteride be used for?

A

hirsutism in women in combo with anti-androgens

63
Q

How does sildenafil work?

A

inhibits phosphodiesterase 5, so you don’t get the breakdown of cAMP and the vasculature in the penis doesn’t regain tone - keeps erection going

64
Q

What shouldn’t you use the PDE-5 inhibitors with?

A

nitrates or beta blockers

65
Q

What are the syde effects if PDE-5 inhibitors?

A

headache, flushig , dyspepsia and nasal congestion

ER Week 4 (15 decks)

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