Male Reproductive Physiology Flashcards
What is the temperature that the testes should be kept at to maintain appropriate spree development
35C
- this is 2-3 degrees lower than normal body temp
Cremaster reflex, panpiniform plexus countercurrent exchange, sweat glands and scrotal skin all take part in maintaining this temp
What are the three accessory glands that contribute to semen secretions
Seminal vesicles
Prostate gland
Bulbourethral gland
What is the thick connective tissue capsule surrounding the testies?
Tunica albuginea
What cells produces sperm in the testies?
Seminiferous tubules
- contain spermatogenesis cells (actually make sperm)
- also contain Sertoli cells (regulates spermatogenesis
- sperm matures startling from the basal Lamina -> luminal surface of the seminiferous tubule
They are controlled by the leydig cells that are found adjacent to the tubules in the interstital space
- leydig produces testosterone and promotes spermatogenesis regulation
Why is the Sertoli cell tight junctions between Sertoli cells importaint?
called the blood-testies barrier
Blocks paracellular diffusion which promotes proper nutrient delivery and not too fast but not slow sperm maturation
Major functions of Sertoli cells
Maintains the testies-blood barrier
Phagocytosis of debris
Production of androgen binding protiens (ABPs)
Production of anti mullarian hormone
Aromatization of local testosterone to estradiol
- via P-450 aromatase enzymes
Forces sperm to move towards epididymis (no reflux)
- *Releases inhibin in response to FSH stimulation which exert negative feedback on the HPT axis to inhibits FSH secretion
- are a member of the TGF-B family
- works on intracellular JAK/Stat pathway**
4 phases of spermatogenesis
1) golgi phase
- involves packing of hydrolytic enzymes and form acrosomal granule-containing acrosomal vesicles
- also begins formation of flagellar axoneme and connecting piece
2) cap phase
- acrosomal vesicle enlarges and forms the acrosome
3) acrosomal phase
- flattened spermatids and the entire cell elongates and the mitochondria conglomerate
- also forms “Manchette” which is a cylindrical collection of microtubules which elongates the spermatid
- turns into the spermatozoon
- also forms the annulus
4) maturation phase
- spermatids release excess cytoplasm which frees the spermatozoa from the syncytium
- are nonmotile until they undergo capacitation in the female reproductive tract
- Sertoli cells phagocytosis the remains
Gametogenesis in males
Germ cells are spermatogonia that have not progressed past mitosis until puberty
Once they hit puberty = mitosis begins and then meiosis also occurs
Spermatogonium (46 2N) -> primary spermatocyte (46 4N) -> secondary spermatocytes (23 2N) -> spermatid (23 N)
Where is the primary location for storage of sperm
Epididymis
How much % or the semen is sperm?
10%
70% = seminal vesicle fluid
20% = epididymis, prostate glands and bulbourethral fluids
Ampulla of the vas deferens fluid
Mixes with sperm during sexual arousal
- contains citrate and fructose and helps sperm survive outside of the epididymis
Seminal vesicle fluids
Fluid rich in fructose, citrate, fibrinogen
Also produces prostaglandins which aid in fertilization in two ways
1) react with cervical mucus and make it more penetratable by sperm
2) induce peristaltic contractions in the female reproductive system to allow the sperm to move better
Prostate fluid
Contains situate calcium and enzymes and is milky With slight alkaline pH
Increases sperm motility and aids in fertilization
Neutralizes acidic environment of vagina
What is the enzyme that stimulates aromatization of the A-ring of the testosterone to estradiol
Aromatase
Steps to testosterone production in leydig cells
LH binds to Gs-protein receptors
- which at the end of that cascade activates cholesterol esterases to cleave free cholesterol
Free cholesterol is sent to the mitochondria and converted into pregnenolone
Pregnenolone is sent to the smooth ER and converted to DHEA and androstenedione to ultimatelyTESTOSTERONE through a serious of steps with 17B-hydroxysteropid dehydrogenase being the main enzyme
Two differences in testes compared to adrenal cortex in the production of testosterone
1) testes dont have 21B and 11B hydroxylases
- cant make glucocorticoids or Mineralcorticoids
2) testes have 17B-hydroxysteroid dehydrogenase enzymes which converts androstenedione-> testosterone
- this is why the testies always produce testosterone and never DHEA and androstenedione
How does LH stimulate steroidogenesis
1) phosphorylation of cholesterol esterase (activates it)
- generates cholesterol molecule from cholesterol ester
2) activation of CYP11A1 (cholesterol desmolase via Gs protein stimulation
- promotes cholesterol -> pregnenolone
Testosterone levels in the blood
An adult male produces 6-7 mg a day
- diffuses into blood immediately after being synthesized in leydig cells
- this amount slowly declines starting at age 50 and reaches about 4 mg per day in 70s
2-3% of hormone is actually free
30-40% is bound to albumin
60% is bound to SHBG that binds both estradiol and testosterone (higher affinity for testosterone though)
- this binding both inactivates testosterone and estradiol as well AA’s increases its half life
- liver damage decreases SHBG which can casue free levels of testosterone and estrodiol to increase
Fate of testosterone in blood
Varies, but primarily functions as a pro hormone and is converted to biologically active DHT by 5-a reductase or into estradiol by aromatase enzymes
DHT is produced because it has higher binding affinity for the androgen receptor and is 2-3x more potent than testosterone
- **is the most potent natural androgen
Affects of testosterone vs DHT
Testosterone
- internal male genitalia differentiation
- increases muscle mass
- aids in growth spurts
- undergoes all “puberty aspects”
DHT
- external male genitalia differentiation
- male hair pattern and baldness
- prostate growth
- sebaceous glands
How do finasteride and dutasteride work to treat benign prostatic hyperplasia
They inhibit 5a-reductase which is required to peripherally convert testerosterone to DHT
- one of DHT’s effects are to increase hyperplasia fo the prostate
How does estrogen work in males?
Unknown completely, but there is a known effect on bone maturation and biology since aromatase deficency in males results in excessively tall stature and delayed closure of the epiphyseal plates
Kallmann syndrome and HPT axis
These patients have a tertiary hypogondotropic hypogonadism dysfunction
This is casued by a mutation in the KAL gene which results in GnRH neuronal precursors to inproperly move to the cribiform plate instead of the hypothalamus
- this also results in loss of smell (anosmia)
What is follistatin
A protein hormone made by the serotoli cells with several isoforms that binds and deactivates activin and also induces paracrine signaling onto leydig cells to develop sperm better
- activin has unknown effects
How is GnRH released
In a pulsitile fashion
- also causes FSH and LH to be secreted in a pulsitile fashion as well
** this is important since a continuous secretion of GnRH results in sensitization and down regulation of the GnRH receptor, but a pulsitile does NOT DO THIS**
How does GnRH, FSH and LH levels change with respect to age
Fetus and infancy
- high levels of FSH
- moderate levels of LH
- generally no GnRH
Puberty
- GnRH now takes over and starts secreting in a pulsitile fashion
- LH and FSH release in pulsitile fashion with LH being higher than FSH
Menopause/senescence
- FSH and LH levels get really high chronically and inhibit GnRH release as well as induce desensitization to FSH/LH receptors
Corticosteroids affects on inhbitng GnRH based on age
Lower doses are needed in infancy
Higher doses are needed to achieve the same effect in once puberty kicks in-right before senescence
This is due to the age dependent feedback sensitivity to the
What is the earliest detectable secondary sexual characteristics in girls and boys
Breasts = girls
Testicular enlargement = boys
Effects of anabolic steroids they in males on LH/FSH and sex steroids
Increases testosterone and DHT in blood but low in the testicles
Decreases LH and FSH
- *this causes a decrease in spermatogenesis since the rates of intratesticular testosterone is decreased due to negative feedback on anterior pituitary from testosterone and DHT levels**
- in order to maintain spermatogenesis, intratesticular testosterone must be 100x higher than blood levels
Erection in males
Is a neuro vascular event that is parasympathetic induced from sexual arousal
- the parasympathetic cavernous nerves induce vascular smooth muscle dilation in the helicine arteries via Nitric Oxide release
- Nitric Oxide induces GCMP which induces relaxation and GMP levels in smooth muscles and arteries
Sperm release pathway = “SEVEN UP”
- Seminiferous tubules
- Epididymis
- Vas Deferens
- Ejaculatory ducts
- Nothing
- Urethra
- Penis
