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Hormonal & Reproductive Week 3 - WLB > Male Reproductive Physiology - Trachte > Flashcards

Male Reproductive Physiology - Trachte Flashcards

1
Q

How many days does it take to develop a mature sperm?

A

about 64 days

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2
Q

Spermatogenesis is positively correlated with what hormone levels?

A

Testosterone levels

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3
Q

What are the components of the Hypothalamic-Pituitary-Gondal Axis?

A

Hypothalamus => GnRH

Anterior Pituitary => FSH (stimulate sertoli cells) / LH (stimulate Leydig cells)

Testis => Inhibin (inhibits FSH release) / Testosterone (negative feedback)

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4
Q

What receptors does FSH stimulate?

A

Gs-alpha => Adenylyl cyclase

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5
Q

What receptors does LH stimulate?

A

Gs-alpha => Adenylyl cyclase

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6
Q

What protein carries Testosterone in fluids?

A

Androgen-binding protein (ABP)

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7
Q

What is the relationship between Sertoli cell number and daily sperm production?

A

Each Sertoli cell supports a fixed number of germ cells: There is a simple linear relationship between Sertoli cell number and daily sperm production.

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8
Q

What is the volume of distribution of Testosterone?

A

Lipid-soluble => 1L/kg => distributes into the whole body because it is fat soluble

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9
Q

What would happen if you had a FSH-secreting tumor?

A

Increased FSH
Increased Sertoli cell stimulation
Increased Inhibin
No change in GnRH, LH, or Testosterone

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10
Q

What would happen if pt is taking androgen supplements?

A

GnRH decreased
FSH/LH decreased
Testosterone increased

***Testis would shrink.

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11
Q

What are the 8 functions of Sertoli Cells?

A
  1. Provide Sertoli cell barrier to chemicals in the plasma
  2. Nourish developing sperm
  3. Secrete luminal fluid, including androgen-binding protein
  4. Respond to stimulation by testosterone and FSH to secrete paracrine agents that stimulat sperm proliferation and differentiation
  5. Secrete the protein hormone inhibin, which inhibits FSH secretion
  6. Secrete paracrine agents that influence the function of Leydig cells
  7. Phagocytize defective sperm
  8. Secrete, during the embryonic life, Mullerian inhibiting substance (MIS), which causes the primordial female duct system to regress
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12
Q

Low Leydig Cell Numbers are correlated with levels of hormones?

A

decreased Testosterone levels

increased Gonadotropin levels

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13
Q

What causes Andropause +/- androgen deficiency with aging?

A

Decrease in testicular function

  • loss of spermatocytes, Leydig cells, Sertoli cells
  • decrease of testosterone production
  • compensatory increases in secretion of GnRH and gonadotropins (FSH and LH)
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14
Q

What are the symptoms of Andropause +/- androgen deficiency with aging?

A

+/-erectile dysfunction

Weight gain due to metabolism shifts, reduced activity, gynecomastia

Thought to be due to shift in estrogen:testosterone ratio

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15
Q

How do you diagnose Andropause +/- androgen deficiency with aging?

A

measurement of morning Total Testosterone (need more than one value)

May follow up with FSH/LH levels

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16
Q

What is the treatment for Andropause +/- androgen deficiency with aging?

A

hormone replacement

sleep, eat well, exercise

Viagra-like drugs for erectile dysfunction

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17
Q

What are the actions of Testosterone?

A

Nuclear transcriptional regulator (binds to Androgen Receptor (AR) and forms homodimer):

  • **Anabolic =>
  • stimulate protein synthesis
  • build muscle
  • bone maturation (close epiphyses due to conversion to estrogen)
  • androgenic effects (facial hair growth, muscle development, sperm production)
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18
Q

What are the GnRH analogs?

A

Synthetic human: Gonadorelin

Analogs: Leuoprolide, Goserelin, histrelin, nafarelin, triptrorelin

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19
Q

What drug acts by inhibiting the conversion of Testosterone to DHT?

A

Finasteride (5-alpha reductase inhibitors)

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20
Q

Androgen antagonists

A

Flutamide, Bicalutamide, Spironolactone

21
Q

What drug acts by inhibiting the effects of DHT on the penis?

A

Sildenafil (phosphodiesterase-5 inhibitor)

22
Q

What are the four target tissues for testosterone?

A

Muscle

Seminal vesicle

Epididymis

Bone

23
Q

Approximately how much testosterone is produced daily by men?

A

approximately 8 mg of testosterone are produced daily

  • 95% is produced by the Leydig cells
  • 5% by the adrenals
24
Q

What is the difference in circulating testosterone levels in men and women?

A

Males: 0.6 mcg/dL => Testicular, adrenal (and made locally in other tissues eg prostate gland)

Females: 0.03 mcg/dL => Adrenals and ovarian derived and other tissues

25
Q

What are the three target tissues for Dihyrotestosterone?

A

Prostate

External Genitalia

Skin

26
Q

Androgens promote the health and function of what?

A 
Seminal vesicle
Prostate
Genital tract
External genitalia
Hair growth patterns
Voice Change
27
Q

Androgens have what anabolic effects?

A

Muscle building => Positive nitrogen balance; increase in protein synthesis (easier to develop muscle)

Bone growth and closure of epiphysis (conversion of testosterone => estradiol)

Sodium and water retention (interaction with mineralcorticoid receptors)

28
Q

In what two situations is androgen hormone replacement warranted?

A

Hypogonadism (low androgen production)

Hypopituitary dysfunction

29
Q

How are synthetic androgens metabolized?

A

1st pass metabolism for natural androgens; reduce first pass for synthetics

  • Weak or inactive metabolites
  • Metabolites conjugated
30
Q

Methyl testosterone

A

Testosterone analog

Orally active
Esterification suppresses absorption
Depresses metabolism
Hepatotoxic => Acute Cholestasis (~1% of users), with chronic use increase tumor incidence

USE: testosterone hormone replacement

31
Q

Oxandrolone

A

DHT derivative

Orally active

DHT derivative => Cannot be converted by aromatase

low risk of hepatotoxicity

anabolic steroid => promotes muscle growth

32
Q

What are the adverse effects of androgen therapy?

A

Growth interruption (premature bone closure) in growing youth

(Aromatization of androgens to estrogen occurs at bone plates. Estrogen is critical for epiphyseal fusion in both young men and women.)

Priapism (when the erect penis does not return to its flaccid state)

Sodium & water retention

Jaundice

Hepatic carcinoma

Hypogonadism upon cessation due to long-term reduction in hypothalamic-pituitary-gonadal axis

Aggressive behavior

Urinary obstruction

33
Q

What are the gender-specific adverse side-effects of anabolic steroids?

A

Men: Gynecomastia/ testicular shrinkage/impotence/reduce sperm count, Baldness

Women: Menstrual irregularities (shorter lighter, amenorrhea), Clitorus enlargement, Increase in facial & body hair

Both: severe acne, strokes/blood clots, high BP, nausea, bloating, aggressive behavior, mood swings

34
Q

Why are there so many adverse side effects of androgen-anabolic steroids?

A

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

The aromatization of androgen-anabolic steroids to estradiol and related compounds can render many adverse estrogenic effects.

35
Q

What is the purpose of medical castration?

A

To interfere with precocious puberty

***To treat androgen dependent cancers.

Reduce libido

36
Q

What drugs are used for medical castration?

A

***Androgen receptor antagonists

Nonpulsatile GnRH agonists

Nonpulsatile GnRH antagonists

37
Q

Why don’t GnRH agonists or antagonists wipe out all adnrogens?

A

they don’t wipe out locally produced androgens in other tissues

some hormones are made locally in adrenal glands (e.g., androstenedione and dehydroepiandrosterone) and in other tissues locally (e.g. prostate, external genitalia for DHT)

***If the goal is to reduce androgen receptor signaling in the prostate gland => need to use androgen receptor antagonists and/or 5-alpha reductase inhibitors and/or GnRH antagonists.

38
Q

Which two drugs are nonsteroidal “pure” receptor antagonists, used in advanced prostate cancer, and have adverse side effects such as gynecomastia and hepatoxicity?

A

Flutamide and Bicalutamide

Typical scenario: Bicalutamide + GnRH agonist or orchidectomy

39
Q

What is the MOA of GnRH (LHRH) Agonists?

A

Bind to GnRH receptors and stimulate the release of gonadotropins FSH and LH for therapeutic purposes. Single or pulsatile use is stimulatory. Continuous delivery shuts down the HPG axis (after short-term increase).

40
Q

What drug is used for functional assessment of gonadal response or for male infertility (3-6 months of pulsatile infusion improves sperm numbers)?

A

Gonadorelin

41
Q

What drug is a synthetic analog of GnRH used for medical castration in cancer?

A

Leuprolide

42
Q

What drug is a GnRH antagonist that is FDA approved for men with advanced prostate cancer and is used in chemical castration or for treatment of BPH?

A

Degarelix

43
Q

Which two drugs are FDA approved for assisted reproduction in ovarian hyperstimulation, and blocks premature LH surge in females?

A

Ganirelix and Cetrorelix

44
Q

What is the major difference between GnRH agonists and GnRH antagonists?

A

GnRH antagonists do not have an initial LH/FSH hypersecretory phase (associated with an immediate androgen flare prior to ultimately shut down HPG axis and decrease in androgens).

45
Q

What drug inhibits conversion of Testosterone to DHT (dihydrotestosterone), and is androgen specific for growth and maintenance of prostate gland in BPH/prostate cancer and male pattern baldness?

A

Finasteride

46
Q

What are the 6 steps in the physiology of erection?

A
  1. Parasympathetic stimulation causes production/release of Nitric Oxide (NO)
  2. NO activates soluble Guanylyl Cyclase (GC) in vascular smooth muscles
  3. induces increase in intracellular cGMP
  4. cGMP promotes arteriole dilation which causes penile engorgement (tumescence).
  5. Phosphodiesterase-5 in vascular smooth muscle degrades cGMP
  6. Venodilation ensues which results in a flacid penis.
47
Q

What two drugs are PDE-5 inhibitors that enhance the effects of NO by inhibiting the enzyme that normally breaks down cGMP and consequently prolong erection?

A

Sildenafil (Viagra) and Tadalafil (Cialis - 4x longer duration)

48
Q

What is the negative feedback caused by Testosterone?

A

Inhibits LH directly in the anterior pituitary

Inhibits GnRH directly in the hypothalamus

Inhibits FSH indirectly by inhibiting GnRH

Hormonal & Reproductive Week 3 - WLB (14 decks)

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