Male Reproductive Physiology

Question 0

What is the important part of the Y chromosome that leads to development of man bits?

Answer 0

Sex-Determining Region, SRY
Also known as the Testes Determining Factor, TDF
In this region, a transcription factor that alters transcription of genes for testicular differentiation from the bipotential gonads in the fetus. This differentiation then leads to increased testosterone production.

Question 1

Three types of sexual identification and explanation.

Answer 1

Genetic - Chromosomes
Gonadal - Presence of ovaries or testes
Phenotypic - Internal and External paraphernalia. ;)

Question 2

What is the bimodal pathway towards sexual differentiation?

Answer 2

Indifferent gonad
Either presence or absence of SRY/TDF
PRESENCE: Development of Testes, with Sertoli and Leydig cells that produce antimullerian hormone and testosterone, respectively, and both of which aid in the development of phenotypic male reproductive components.
ABSENCE of SRY/TDF: “Default” development of bipotential fetal gonads into ovaries, which then DO NOT produce antimullerian and testosterone, and therefore develop female internal and external reproductive lady bits.

Question 3

What do Sertoli cells do? And what does that product do?

Answer 3

Secrete Anti-Mullerian hormone (AMH) -> SAM
AMH is a growth factor that PREVENTS formation of Mullerian ducts (part of female tract, the default developmental track). Regression of those ducts by apoptosis.
Also make Inhibin (part of negative feedback loop).
Also make ABP (androgen binding protein).
Also make Aromatase (produces estrogens).

Question 4

What do Leydig cells do? What does product do?

Answer 4

Secrete Testosterone, DHT (Dihydrotestosterone, STRONGER), and IGF-3

Testosterone: Development of internal genitalia
DHT: External development
DHT, IGF-3: Testicular descent into scrotum
All three: Embryonic prostate development

Question 5

Problems in meiosis can lead to chromosomal abnormalities. What are they?

Answer 5

XO - Gonadal dysgenesis, Turner Syndrom. Small female, no sexual maturation, etc.
XXX - No obvious phenotye
YO - lethal
XXY - Klinefelters syndrome (1/1000 males) - small testes, reduced fertility, can have multiple X chromosomes. The SRY of the Y chromosome has a hard time “outshining” the X chromosome activities. Male Gender Identity

Question 6

HORMONAL causes of aberrant sexual differentiation

Answer 6

1. Virilizing Adrenal Hyperplasia in female fetus. Called female pseudohermaphroditism (usually “looks” more like a male). Too much androgen from mom, can get an ovarian tumor, treatment depends on gestational age.
2. Male pseudohermaphroditism (usually looks more like female) - Androgen resistance (testicular development incomplete). 5alpha-hydroxylase deficiency which blocks testosterone synthesis. Adrenal hyperplasia blocks pregnenolone formation.

Question 7

When does puberty start? In males?

Answer 7

When hormones start flowing in greater quantity. OH, TEEN ANGST!

In males, GnRH (gonadotropin releasing hormone), which is always present in low levels, kicks up and starts to be released in waves (“pulsatile”) from the arcuate hypothalamic nucleus. This gives us wave release of LSH and FSH, as well. Waves are regulated by feedback mechanism with testosterone inhibiting release of LSH and FSH.

Question 8

Control of reproductive hormone release in males.

Answer 8

GnRH from arcuate hypothalamic nucleus causes release of LH and FSH from pituitary. These ultimately lead to production of testosterone, which inhibits GnRH release at the top, in a negative feedback loop.

Question 9

LH and FSH. What are they? What do they do?

Answer 9

LH = Leutinizing hormone. Stimulates Leydig cells to make testosterone.

FSH = Follicle-stimulating hormone that stimulates the Sertoli cells to make anti-Mullerian hormone and inhibin to stop development down the female track (and therefore ultimately help in the development of Sperm).

Question 10

Hypothalamic-Pituitary-Gonadal Axis. Tell me about it.

Answer 10

The negative feedback loop between the hypothalamus (GnRH release), anterior pituitary (LH and FSH), and the testicles (Testosterone, estradiol, sperm production, etc.).

Question 11

Tell me about the Inhibins made in the Sertoli cells?

Answer 11

Part of the HPG axis, they are made by Sertoli cells in response to FSH and are Transcription Growth Factors. The presence of inhibin in blood INHIBITS production of a part of FSH in pituitary, thus slowing down production.

Activans are similar to inhibins, but attack inhibins at pituitary, and so are another check and balance on the system. I don’t know where they are made.

Question 12

Through what mechanisms does Testosterone WORK?

Answer 12

Three mechanisms:

1. Activates androgen receptor (though DHT is more powerful at this).
2. Converts to DHT by 5alpha-reductase.
3. Converts to estradiol (an estrogen) by aromatase.

Question 13

Via the various mechanisms through which it takes action, what does Testosterone do?

Answer 13

1. Direct effect on androgen receptors has effect on development of internal genitalia (wolffian development), skeletal muscle (BIGGER, STRONGER!), and bone development
2. Conversion to DHT leads to development of external genitalia throughout life stages, and has effect on hair follicles.
3. Conversion to Estradiol acts on estrogen receptors which close the growth plates in bone and increases libido.

Question 14

What are precursors of testosterone and what is the crucial enzyme in testosterone production?

Answer 14

Pregnenolone and Androstenedione. (Ultimately all from forms of cholesterol.)

17beta-hydroxysteroid dehydrogenase.

Question 15

What is important about Testosterone in circulation? If T levels are constant, what controls the amount of FREE T in circulation?

Answer 15

Only free is active. Most (98%) is bound to proteins, either SHBG (Sex hormone binding globulin), albumin, or androgen-binding protein (ABP) in testes.

SHBG synthesis is stimulated by estrogen and inhibited by androgens, therefore regulating the amount of free testosterone available.

Question 16

Ironically, Testosterone actually turns into estradiol, an estrogen, for some necessary action. How does it change, and what does the estradiol do?

Answer 16

Aromatase to convert. Some in testes, mostly in adipose tissue. Estradiol then bound to globulins in blood, just like T.
In males, Estradiol is part of negative feedback loop on GnRH production (inhibits hypothalamus secretion) and works to close epiphyseal lines and strengthen bones. Without it, guys have weaker bones than they need.

Question 17

What converts T to DHT? And where?

Answer 17

5alpha-reductase. Some (10%) done in testes, but mostly at target organ sites, and depends on the amount of 5alpha-reductase being expressed there. Mostly at skin and prostate.

Question 18

Give a list of things Testosterone does.

Answer 18

Differentiation of testes in utero.
Growth of penis and seminal vesicles (to the delight of all).
Pubertal growth spurt.
Bone development (VIA ESTRADIOL)
Increased muscle mass.
Deepening of the voice (Benedict Cumberbatch, YOU SLAY ME).
Spermatogenesis.
Negative Feedback loop of gonadotropins from hypothalamus (VIA ESTRADIOL)
Negative feedback loop on LH from anterior pituitary.
Libido (again, to the benefit of all. Sometimes. Not at 2am when I’m already asleep.)

Question 19

Molecular mechanism of androgens.

Answer 19

They bind to Androgen receptors in cytosol of target cells, migrate to nucleus, and then binds to specific sequences of DNA aclled Hormone Response Elements that attract transcription equipment to upregulate transcription. These gene sequences are ONLY TRANSLATED if they are properly “started” with the androgen-binding receptors. They are dependent on that machinery to attract transcription factors.

Think about what would happen if the receptors are messed up!

Question 20

Anabolic effects of testosterone.

Answer 20

Increased protein synth.
Blockage of cortisol, so that proteins don’t break down. Hence, the gaining of muscle mass.
Retention of various ions and charged particles.
Increased kidney size.
The growth effects (protein stuff) cannot be separated from the “androgenic virilizing” effects, which are basically the “making you look and be like a man” effects (testosterone production effects).

Question 21

Pharmacological use of REAL HUMAN androgens. Not super-concentrated fake ones.

Answer 21

T deficiency.
Endometriosis (treat with a weak androgen).
Muscle-wasting with AIDS.
Angioedema (treat with weak androgens to stimulate hepatic enzyme that is important to maintain skin integrity).

Question 22

What makes synthetic androgens different?

Answer 22

Usually, they are testosterone ESTERS, which have a longer absorption time and half life, so they stick around longer and have greater activity. Also, many can be taken by mouth.

FAILED attempts to separate the anabolic and virilizing effects. They always go together!

Question 23

How do we control development and overgrowth of the prostate?

Answer 23

Prostate develops from DHT, which is testosterone-dependent. Therefore, we try to lower T levels if prostate too big. We can reduce the amount of 5alpha-reductase (drug called Finasteride, which also affects male-pattern baldness), or agonize the GnRH secretion to reduce overall T (drug called Leuprolide).

Question 24

Male aging and hormonal release.

Answer 24

Gradual Decrease in testosterone.
Decrease in sperm production (but not ever really petering all the way out).
Increase in SHBG - less free Testosterone
Decrease in all the effects that Testosterone has (energy, libido, muscle mass, bone density, cognitive function, mood, etc. Poor dudes.)

Question 26

Nervous regulation of Male Genitalia. What directs what and what does that second what do?

Answer 26

Point and Shoot!
Parasympathetic effects on muscarinic receptors in penis causes erection (PNS on the PENIS causes POINT).
Sympathetic enervation to alpha1 receptors causes ejaculation (SNS cause SHOOT).
Other neurotransmitters also at play.

Question 27

Stimulators of GnRH

Answer 27

Norepi, Neuropeptide Y, leptin

Question 28

Inhibitors of GnRH secretion

Answer 28

Beta endorphin, melatonin, IL-1, GABA, TESTOSTERONE (after conversion to estradiol, leads to feedback loop on GnRH)

Question 29

2 Reasons males would be unresponsive to estradiol

Answer 29

Aromatase Defect (cant convert T to estrogen) or Lack of estrogen receptor

Results in osteoporosis AND epiphyseal non-closure [long bones keep growing)

Aromatase defect can be treated with estradiol, lack of receptor cannot

Question 30

What is a Hormone Response Element?

Answer 30

Sections of DNA that hormone (in this case androgen) transcription factors respond and bind to to upregulate receptors & production

Question 31

Regarding Anabolic Steroids: what effect does testosterone and its esters have?

Answer 31

gynecomastia (xs testosterone-> converted to xs estrogen -> breast tissue development in males)

Question 32

Regarding Anabolic Steroids: What effects do the 17 alkylated androgens have?

Answer 32

Liver damage (hepatitis, hepatic cysts, hepatocellular cancer) and, associated with this, lowered HDL

Question 33

Regarding Anabolic Steroids: What effects do ALL androgens have?

Answer 33

suppression of gonadal function, decreasing testicle size, deepening voice, body hair growth, aka. your typical sports-related steroid effects including ROID RAGE (increased aggressiveness)