Male Repro Physio

Question 1

What gene on the Y chromosome is crucial for male development? What protein does this gene code for? Name 3 other genes/proteins that are important for male development.

Answer 1

SRY gene is found on the Y chromosome. It codes for testis-determining factor (TDF). SOX-9, SF-1 and Androgen Receptor are also crucial for male development.

Question 2

For the development of male gonads, what is the function of testosterone? What of Anti-Mullerian Hormone (AMH)?

Answer 2

Testosterone has a local effect of stimulating the development of the Wolffian Duct into the male internal genital tract. AMH regresses the Mullerian Duct, that would have become the default female internal genitalia.

Question 3

What 3 structures does the Wolffian duct develop into? What of the Mullerian Duct?

Answer 3

Wolffian duct develops into the Seminal vesicles, Vas deferens and Epididymis. The Mullerian Duct forms the Fallopian tubes, Uterus and Upper Vagina (in absence of AMH and testosterone)

Question 4

In the absence of __________ the genital tubercle, urogenital sinus and urethral folds develop into female external genitalia (clitoris, labia minora/majora and lower vagina).

Answer 4

Absence of dihydrotestosterone (DHT) results in female external genitalia.

Question 5

For males, the timed production of _______, ______ and ______ is critical for normal development of the male internal genital tract and external genitalia.

Answer 5

Testosterone, AMH and DHT

Question 6

What are the 3 accessory glands of the male reproductive system and their functions?

Answer 6

Seminal vesicle - secrete fluid rich in fructose that is a nutrient for sperm.
Prostate gland - secretes alkaline fluid to neutralize acidic environment of vagina.
Cowper’s glands - produce viscous secretion that neutralizes acid and lubricates urethra for sperm passage

Question 7

Name the 2 functions of the testis. What are the 4 stages of spermatogenesis from basolateral side to the lumen of the seminiferous tubules?

Answer 7

Testis are the site of sperm and androgen production. From BM to lumen, maturation goes from Spermatogonium > Spermatocyte > Spermatid > Spermatozoon
“GCTZ = Gonium, cyte, tid, zoon “

Question 8

Describe the significance of tight junctions in the Blood testis barrier. (Provide 2 reasons for their importance).

Answer 8

Tight junctions of BTB prevent harmful substances from entering the adlumenal region and prevent flagellated sperm from entering circulation, which could trigger an immune response.

Question 9

The function of _______ cells is to nourish developing sperm and create the blood-testis barrier. ______ cells secrete androgens and ________ are at Prophase I.

Answer 9

Sertoli cells;
Leydig cells of the interstitium;
Spermatogonia

Question 10

What 3 enzymes do the adrenal cortex and Leydig cells of the testis have in common? What new enzyme is expressed in Leydig cells but not in the adrenal gland?

Answer 10

CYP11A, 3-Beta-HSD, and CYP17 are 3 enzymes found in both tissues. 17-Beta-HSD is found exclusively in Leydig.

Question 11

Testosterone can be converted into the more potent DHT via the _________ enzyme. More than 95% of total testosterone/DHT in adult males can be found in ______.

Answer 11

5-alpha-reductase enzyme found in androgen-responsive target tissues. T/DHT found in the testes, a minority comes from the adrenal gland.

Question 12

Where does most DHT production occur? Provide an example.

Answer 12

DHT is predominantly produced outside the testes in androgen-responsive target tissues such as the prostate.

Question 13

For both males and females ________ is an obligate precursor to estradiol; meanwhile, _____ is the same for estrone. The enzyme responsible for converting both of these reactions is __________

Answer 13

Testosterone = E2 precursor; Androstenedione = Estrone precursor;
Aromatase (CYP19)

Question 14

The body cannot synthesize androgens without what key cholesterol derivative?

Answer 14

Estrogen (E2)

Question 15

LH stimulates _____ cells which secretes _______ that negatively feedbacks ________ production of the hypothalamus and ______ secretion from the pituitary gland.

Answer 15

Leydig cells secrete testosterone which negatively feedbacks GnRH and LH secretions

Question 16

FSH gonadotropin stimulates _______ cells which secretes _______ that negatively feedbacks _______ and ______ on HPA.

Answer 16

Sertoli cells secrete inhibin which suppresses FSH (from pituitary gland) and GnRH from hypothalamus.

Question 17

_________ is secreted from multiple tissues (including the pituitary gland) to act in a _______ manner in gonadotropes.

Answer 17

Activin acts in a paracrine manner to stimulate FSH and maybe GnRH secretions. This is the opposite function to that of inhibin.

Question 18

GnRH is secreted into the pituitary gland in a ________ manner, with one event every _____ hours in the post-pubertal male.

Answer 18

PULSATILE manner;

1 pulse per 3 hours

Question 19

Why is there an increase in gonadotropin secretion rate in both males and females during senescence? Which gonadotropin is in greater quantity?

Answer 19

Due to the lower levels of androgens (estradiol and testosterone) than in adulthood, there is less negative feedback at the HPA which explains why gonadotropins FSH and LH rise. FSH is in greater quantity than LH.

Question 20

In the adult reproductive period what gonadotropin hormone is in greater quantity? Describe one difference in secretion between males and females at this stage of life.

Answer 20

LH > FSH in both males and females. Menstrual cycles explain the fluctuating secretions of gonadotropins every 28 days; whereas males are elevated but plateaued.

Question 21

In males, plasma testosterone is _____ in adulthood but _________ during senescence. How does the latter stage relate to gonadotropin levels?

Answer 21

Testosterone is high in male adults, but decreases during senescence. Gonadotropin levels rise as testosterone tapers off.

Question 22

What is Testosterone’s effect on Sertoli cells?

Answer 22

Testosterone stimulates Sertoli cells to make more androgen binding protein and TGF’s to help speed the process of spermatogenesis.

Question 23

Describe 2 androgen signaling pathways that circulating testosterone can take once it enters the cell of an effector tissue.

Answer 23

1. Testosterone (T) can be converted to Estradiol (E2) and bind to estrogen receptor.
2. T can be converted to DHT via 5-alpha-reductive which binds to androgen receptor to homodimerize and elicit secondary male development characteristics.

Question 24

The prostate gland is entirely dependent on what androgen for growth?

Answer 24

DHT

Question 25

Pertaining to prostate cancer, what is the best way to inhibit production of androgens, aside from surgery?

Answer 25

Androgen secretion can be inhibited via Androgen ablation therapy which involves the use of GnRH agonist to disrupt the pulsatile signaling of the HPA. This effectively shuts down gonadotropins altogether resulting in less DHT for prostate cancer to thrive on.

Question 26

What can 5-alpha-reductase inhibitors (such as finesteride) be used to treat?

Answer 26

Finesteride can be used to treat prostate cancer by blocking the conversion of testosterone to DHT. Low DHT may stunt the progression of prostate cancer/ BPH.

Question 27

Describe the mechanism by which Cushing’s Syndrome is related to Male Hypogonadism.

Answer 27

This is known as Secondary Gonadotropin Deficiency. It involves high levels of Cortisol associated with Cushing’s syndrome that can block the Hypothalamic-Pituitary Axis (HPA) secondarily. This blocks ACTH and LH secretion from the pituitary gland. This in turn results in less stimulation to gonadal development.

Question 28

What 2 genetic disorders result in primary gonadal abnormalities?

Answer 28

1. Klinefelter’s syndrome (47 XXY) = meiotic non-disjunction (paternal or maternal); elevated gonadotropin + estrogen levels; low testosterone; atrophic Leydig cells (1 in 500 males)
2. 46 XX Male syndrome = lack of SRY gene from a chrmosomal translocation (1 in 20,000 males)

Question 29

List at least 3 ways to which testicular failure can result in a primary gonadal abnormality.

Answer 29

Viral orchitis (MUMPS or Zika virus), autoimmune disease, drugs (cyproterone, ketoconazole, ethanol, marijuana in large amounts)

Question 30

Describe the significance of Cryptorchidism.

Answer 30

An undescended testicle can result from a disruption in testosterone. If left untreated, it can lead to infertility with increased risk factors of testicular cancer and inguinal hernias. This normally corrects itself in the 1st year of life (small surge of testosterone may play a role).

Question 31

What are some AR defects in 46 XY males?

Answer 31

Testis develop normally but the ability for testosterone to act on the Wolffian duct is inhibited. Since not all mutations are equal, the feminization phenotype can vary depending on how much inhibition occurs. This is clinically termed “Androgen resistance” as neither DHT nor T can signal effective tissue changes.

Question 32

What are some 5a-Reductase defects in 46 XY males?

Answer 32

Autosomal inheritance of 2 defective alleles can impair the ability of Testosterone to becoming DHT. The degree of inhibition depends on the severity of the mutation.

Question 33

Describe the difference between complete and partial androgen resistance.

Answer 33

Complete AR = Male pseudo hermaphroditism. It results form an AR knockout in which there are higher than normal levels of E2 that results to more female secondary characteristics. This differs from Partial AR = Reifenstein’s syndrome that can present in an affected individual as having ambiguous genitalia. In this, the spectrum of the phenotype depends on the severity of the mutation.

Question 34

What are the clinical features of 5a-Reductase Deficiency?

Answer 34

This autosomal recessive disorder can present as ambiguous genitalia, partial masculinization at puberty, sparse body hair and elevated T:DHT ratio. DHT levels are low due to absence of these enzymes resulting in a spectrum depending on severity of the mutation.

Question 35

Why does a complete KO associated with Androgen Resistance result in a more a greater degree of feminization than other genetic abnormalities?

Answer 35

Since androgens are converted to estrogen and testosterone can still be turned to E2 this can result in higher than normal levels of E2 = female secondary characteristics.