Physiology of Male Reproductive System

Question 1

What are the functional compartments of the male reproductive tract?

Answer 1

Seminiferous Tubules

• Exocrine function
• Germ cells
  
  • Produce sperm

Interstitial Tissue

• Endocrine
• Leydig cells
  
  • Androgen secretion

Question 2

Androgens are ________ steroids.

Answer 2

C19

Question 3

Majority of 5-a dihydrotestosterone is formed in _____________.

Answer 3

Peripheral tissues

Question 4

What are the major steroids that are produced by the testis?

Answer 4

• Testosterone
  
  • ​Activity of 100
• Androsterone
• Androstenedione
• 5-a-dihydrotestoterone
  
  • ​Activity of 250

NOTE: Some 5-a-dihydrotestosterone is made in the testes but the majority is made in peripheral tissue

Question 5

How does cholesterol get into the leydig cells?

Answer 5

• De nove synthesis from acetate
• Cholesterol is brought in by LDL

NOTE: This takes place in the mitochondria of the cell

Question 6

What is the first step in the synthesis of testosterone from cholesterol?

Answer 6

• Conversion of cholesterol to pregnenolone with CYP11A1 (cholesterol side chain cleavage) enzyme

NOTE: This is the control point for this system

Question 7

Which protein is responsible for bringing cholesterol into the mitochondria of leydig cells?

Answer 7

• StAR protein
  
  • ​Stimulated by LH

Question 8

What are the two loops through which testosterone can be formed from cholesterol? Which loop is most common? What is the pathway for each loop?

Answer 8

• Delta 5 Loop
  
  • ​Most common
  • Cholesterol-> Pregnenolone-? 17 OH-pregnenolone-> DHEA (dehydroepiandrosterone)-> Androstenediol-> Testosterone
• Androstenedione
  
  • ​Cholesterol-> Pregneolone-> Progesterone-> 17-OH-progesterone-> Androstenedione-> Testosterone

Question 9

__________ is the major source of estradiol in men.

Answer 9

Androstenedione

NOTE: Androstenedione may be converted to estrone and subsequently estradiol in peripheral tissue.

Question 10

What are the major sex steroid binding proteins?

Answer 10

• Testosterone- Estrogen Binding Protein (TEBG)
  
  • High affinity binding site
  • Distribution in blood: 30-40%
• Albumin
  
  • Low affinity binding site
  • Distribution in blood: 50-60%

NOTE: Only about 0.5-3% of testosterone is traveling freely in blood

Question 11

Which hormone has the highest binding affinity for Testesterone-Estrogen Binding Protein (TEBG)?

Answer 11

• Dihydrotesterone (DHT)- 100
• Testosterone- 33
• Estradiol- 25

NOTE: A decrease in TEBG will free up more of the ligand with the highest affinity and less of the ligand with the lowest affinity.

Question 12

What are two fates of androstenedione?

Answer 12

Can be converted to:

• Testosterone, which can then be converted to:
  
  • Estradiol
  • Dihyrotestosterone
• Estrone

Question 13

Roles of estradiol

Answer 13

• Bone resorption
• Epiphyseal fusion
• Sexual differentiation of brain
• Some behaviors
• Plasma lipids
• Atherosclerosis progression

Question 14

Roles of dihyrdotestosterone

Answer 14

• Prostatic growth
• Skin
• Hair follicles in androgen sensitive areas

Question 15

What is mechanism of testosterone action?

Answer 15

• TBEG attaches to testosterone
• Testosterone comes off, fuses across the plasma membrane into the cell and is acted on by 5-alpha DHT reductase to form DHT
• Testetosterone displaces the HSP chaperone from the androgen receptor
• The androgen receptor is dimerized and phosporylated
• The androgen receptor and testosterone structure enter the nucleus binds to androgen response elements,collects coactivator proteins and eventually activates target genes to cause the biological response.

Question 16

What activites are associated with testosterone and dihydrotestosterone?

Answer 16

• Testosterone- receptor
  
  • ​Feed back regulation of gonadotropin secretion
  • Differentiation of the wolffian duct in utero
• DHT receptor
  
  • ​External genitalia differentiation in utero
  • Virilization during puberty

NOTE: Both testosterone and dihydroxytestoserone interact with the androgen receptor

Question 17

There a rings of _______ cells around the semineferous tubules.

Answer 17

Sertoli

NOTE: Most of the actions of the testes are in the avascular compartment becuase many blood proteins inhibit spermatogenesis

Question 18

What are the two functional compartments of semineferous tubules?

Answer 18

• Adluminal
  
  • Sertoli cells
  • Tight junctions
  • Seminal fluid
• Basal
  
  • On the outside, where we have spermatogonia and mitosis

NOTE: Migration from the basal to adluminal compartment is where the germ cells hit the avascular zone and meiosis starts. This process is control through Sertoli cells

Question 19

Function of Sertoli cells

Answer 19

• Nourish healthy cells and phagocytize damaged germ cells
• Synthesize luminal proteins
• Maintain tubular fluid
• Convert androgens to estrogens
• Site for hormonal modulation of tubular function

NOTE: If Sertoli cells are stimulated with FSH the sertoli cell will communicate with gap junctions, allowing for the germ cells to cross the gap junctions.

Question 20

Which hormones are produced by sertoli cells?

Answer 20

Estradiol (-)

Inhibin (+)

Activin (-)

*These hormones regulate leydig activity

Question 21

Inhibin and folistatin exert feedback supression while activin shows feedback stimulation of __________ secretion.

Answer 21

FSH

Question 22

During hyperprolactinonemia elevated prolactin ___________ (supresses/stimulates) reproduction at the hypothalamic and pituatary levels.

Answer 22

Supresses

Question 23

How can the male reproductive (hypothalamic-pituatary) axis system be assessed?

Answer 23

1. Using clomid

• Clomid is a weak estrogen agonist in most places
• At the anterior pituatary it is a strong estrogen antagonist that can block a lot of the feedback
  
  • Clomid blocks access to the receptor without activating it

2. By blocking feedback, this allows GnRH to go up and we measure a rise in LH and FSH
   * Measures to see if the axis is working properly
3. Injection of HCG

• Let’s you know how well the testes are working
• Measure the rise in testosterone being produced

Question 24

During erection, smooth muscles are _______ (relaxed/contracted).

Answer 24

Relaxed

*Sinusoidal spaces are filled, outflow venules are compressed against the tunica albuginea

Question 25

What are the mechanism of penile erection?

Answer 25

1. Relaxation of trabecular smooth muscle * Parasympathetic input * Decrease in intracellular Ca2+ * Increase in PGE1 * Increase in NO * Decrease in smooth muscle sensitivity to Ca2+ 2. Increased blood flow into cavernosal sinusoids 3. Engorged corpora cavernosa presses venules against tunica albuginea restricting venous outflow

Question 26

Which pathologies lead to gynecomastia?

Answer 26

* Hypogonadism- Klinefelters * Chronic liver disease * Tend to get an increase of TEBG secretion, which takes testosterone out of circulation * Thyrotoxicosis * Neoplasia * Drugs **NOTE:** Anytime there is an elevation of estrogen that's insufficiently blocked by androgens we can see expression of estrogenic activity.

Question 27

What is the major cause of gynecomastia?

Answer 27

* Increased estrogen/androgen ratio (either increased estrogen and/or decreased androgen can accomplish) **NOTE:** Gynecomastia can be physiological, pathological, or idiopathic.

Question 28

What are the 4 types of pathological gynecomastia?

Answer 28

* Deficient testosterone formation * Increased estrogen secretion * Increased extraglandular estrogen formation-Increased substrate * Increased extraglandular estrogen formation- increased aromatase enzyme