Exam #4: Male Reproductive Physiology Flashcards
What is the function of the epididymis?
Remember that the epididymis connects the rete testis to the vas deferens. The functions of the epididymis include:
- Storage, maturation and transporation of sperm
- Development of sperm motility
- Reabsorption of aging sperm
*Note that H+ ions are secreted to maintain the sperm in an inactive state
What is the function of the vas deferes?
Remember that the Vas deferens connects the epididymis to the seminal vesicles. The functions of the Vas Deferens include:
- Storage of sperm in the ampulla
- Transportation of sperm
*Note that the ampulla contracts during ejaculation to propel sperm into the proximal urethra/ allows sperm to mix with prostatic and seminal vesicle fluids
What is the function of the seminal vesicle?
- The seminal vesicle produces roughly 60% of the fluid portion of the ejaculate i.e. semen
- Seminal fluid or semen consists of:
1) Fructose= energy for sperm
2) Prostaglandin= make the cervical environment more favorable for sperm survival & promote peristalsis of the uterus/ fallopian tubes
3) Fibrinogen= coagulation of semen that holds semen in deeper regions of the vagina and cervix
4) Seminogelin= suppresses motility of sperm in the coagulated semen
What is the function of the prostate gland?
The prostate gland secretes a milky fluid that constitutes roughly 39% of the fluid of semen and contains:
1) Ca++
2) Citrate
3) Prostatic acid phosphatase
4) Profibrinolysin= activated to plasmin that dissolves coagulated semen & frees sperm
5) HCO3 (bicarbonate)= neutralizes the acidic environment of the cervix, allowing sperm to become more motile
6) Prostate Specific Antigen (PSA)= hydrolyzes seminogelin, which causes sperm to become more motile
*****Note that PSA is a biomarker for prostate cancer
What is the function of the bulbouretheral gland?
Secretion of mucous into the urethra upon arousal
- Functions as a lubricant in the urethra
- Cleans the lumen of the urethra
*Note that the bulbouretheral gland is also known as “Cowper’s Gland”
What are Leydig cells? What is the function of the Leydig cells?
- Endocrine cells that secrete testosterone
- These cells are contained within the “peritubular compartment” of the testes, or the spaces between the tubules of the testes
What are Sertoli cells? What is the function of the Sertoli cells?
- Sertoli cells are cells contained with in the seminiferous tubules, or in the “intratubular space”
- Functions
1) This is where spermatogenesis occurs
2) Production and secretion of Androgen Binding Protein (ABP), which binds and concentrates testosterone in the area of spermatogenesis
Where is GnRH synthesized and released?
Hypothalamus
*Note that it is released in a pulsatile fashion that is controlled by the pulse generator in the hypothalamus
What is the function of GnRH?
Influences the release of the pituitary gonadotropes
Where is LH produced?
Anterior pituitary
What is the function of LH?
- Binds receptors on Leydig cells and stimulates testosterone production/ secretion
- Testosterone then diffuses to Sertoli cells to facilitate spermatogenesis
Where is FSH produced?
Anterior Pituitary
What is the function of FSH?
Stimulation of Sertoli cells to produce ABP
- ABP concentrates testosterone at the site of spermatogenesis
Why is it important to pulsatile secretion of GnRH?
- Constant high levels of GnRH causes a desensitization of GnRH receptors
- This can lead to a reduction in LH and FSH release
Outline the specific mechanism of action of LH on Leydig cells.
LH induces cholesterol to be converted into Testosterone
- LH binds to a GPCR on the Leydig cell
- cAMP increases (Gas)
- PKA increases
- Increased synthesis of steroidogenic enzymes that control testosterone synthesis
*Note that the testosterone produced by the Leydig cells with diffuse into the Stertoli cells and stimulate spermatogenesis
What is Estradiol? Where is Estradiol produced and what is its function?
Estradiol is a product of testosterone
- Estradiol is produced in the Sertoli cells
- Sertoli cells contain the enzyme Aromatase
- Aromatase converts Testosterone into Estradiol
- Estradiol diffuses back into the Leydig cells
Outline the specific mechanism of action of FSH on Sertoli cells.
Like LH, FSH binds to a GPRC on the Steroli cells
- Gas subunit activation increases cAMP
- PKA is increased
- Aromatase, ABP, and Inhibin are all produced in response to FSH binding to the Steroli cell
How is Testosterone synthesized? Draw & label the synthesis pathway of Testosterone & DHT synthesis. What is the rate-limiting enzyme?
- The rate limiting step of the production of Testosterone is the conversion of cholesterol to pregnolone via Cholesterol desmolase
- Pregnolone is converted by 17alpha-hydroxylase into intermediate products
- 3B-hydroxysteroid dehydrogenase (3B-HSD) makes Androstenedione
- 17B-Hydroxysteroid dehydrogenase cleaves Androstenedione into Testosterone
*****Note that Testosterone is converted into the DHT by 5a-reductase
How does testosterone production change throughout life?
- Spike in the fetal development to form male genitalia
- Spike in the neonate
- Spike in puberty and reaches a peak in adulthood
*Note that Testosterone production is not constant throughout the day either
How is testosterone transported in the blood?
Testosterone binds albumin in the blood & SHBG (sex-hormone-binding globulin)
- Note that the MAJORITY of testosterone is BOUND to albumin or SHBG, only a small amount is actually available
Why is there a decrease in testosterone production with age?
- Synthesis of Testosterone decreases with age
- Increased SHBG with age leads to a decrease in the bioavaliablity of Testosterone
Thus, there is a combinatorial effect of these two mechansisms
What is the risk of testosterone replacement therapy?
Increased risk of prostate cancer
What is the mechanism of Testosterone when it reaches a target cells?
1) Diffuses across membrane of target cell (lipophilic)
2) Binds to the androgen receptor in the nucleus
3) Altered gene transcription
How does the affinity of DHT for the androgen binding receptor compare to Testosterone?
The affinity of DHT is far greater than that of Testosterone
What receptor does estradiol bind to?
Estrogen receptor
What are the effects of Testosterone?
- Internal Genitalia
- Skeletal muscle= increased mass and strength during puberty
- Erythropoiesis= increased production of RBCs, which is why males have a higher hematocrit than females
- Bone= strengthens bone
What are the effects of DHT?
External Genitalia
Hair= increased male hair growth during puberty
What are the effects of Estradiol?
- Bone= main regulator of bone i.e. increased bone density and epiphyseal closure
- Libido
What are the metabolic effects of testosterone?
- Stimulates resting metabolic rate
- Inhibits lipid accumulation in adipocytes, stimulates lipolysis, and inhibits differentiation of adipocyte precursors
Describe the hormonal control of spermatogenesis.
Testosterone & FSH act on the Sertoli cells to induce spermatogenesis
Testosterone
- Stimulates transcription of genes in Sertoli cells that mediate spermatogenesis
- Gets converted to estradiol via Aromatase, which is thought to facilitate spermatogenesis
FSH
- Increases synthesis of ABP–>concentration of Testosterone
- Aromatase= Testosterone–>Estradiol
Why can anabolic steroid administration reduce spermatogenesis?
Anabolic steroids are a derivative of Testosterone that inhibits LH & FSH production via a negative feedback mechanism
- Decrease in testosterone
- Decreased FSH –> significant decrease in ABP
**Unable to concentrate Testosterone at the site of spermatogenesis without ABP
Describe the process of spermatogenesis.
1) Spermatogonia= primordial germ cells that have migrated to the basal compartment of the seminiferous tubules
2) Primary spermatocyte= passes through tight junctions into the adluminal compartment
3) Secondary spermatocyte= 1st round of meiosis
4) Spermatid= 2nd round of meiosis
Maturation of spermatids via spermiogenesis= differentiated mature sperm that are released into the lumen of the seminiferous tubules
What is spermiation?
Release of mature sperm (spermatozoa) into the lumen of the seminifierous tubules
What is spermiogenesis? What are the steps of spermiogenesis?
Spermiogenesis is the process by which spermatids differentiate into spermatozoa or mature sperm
- Under the control of FSH
1) Acrosomal vesicle buds off the golgi apparatus to form the acrosomal cap
2) Centrioles bud to form the flagellum
Why are tight junctions between Sertoli cells important?
Tight junctions provide the blood-testis barrier; after genetic recombination the sperm cells are different enough from self that the body would mount an immune response against them if these tight junctions did not exist
What is the spermatogenic wave?
- Spermatogenesis occurs along the length of the tubules in successive cycles
- New cycles are initiated every 2-3 weeks
This ensures that males are always fertile
What is hypergonadism?
Excess androgen activity that can lead to precocious puberty
Causes include:
- Hypothalamic tumor treated with long term agonist that desensitizes receptors
- Mutations of LH receptor
- Congenital adrenal hyperplasia
- Androgen-producing tumors
What is primary hypogonadism?
Testicular dysfunction leads to a decrease in testosterone production caused by Cryptorchidism or Kleinfelter’s (males with an additional X chromosome)
- Decreased Testosterone leads to lack of negative feedback thus:
- Increased GnRH
- Increased LH & FSH
*Also called hypergonadotropic hypogonadism
What is secondary hypogonadism?
Decrease in circulating gonoadotropins due to a lesion in then hypothalamus or the pituitary gland
- Decrease in circulating gonadotropes
- Decreased testosterone in the setting of low LH & FSH
*Also called hypogonadotropic hypogonadism
What are the stages of the male sexual act? Note whether the stage is PNS, SNS, or spinal reflex induced.
- Erection- PNS
- Lubrication- PNS
- Emission- SNS
- Ejaculation- Spinal reflex
Describe the anatomy of an erection.
1) During arousal there is a PNS induced dilation of the penile arteries or the corpus cavernosum and corpus spongiosum
2) Veins are compressed, maintaining erection
What terminates an erection?
Vasoconstriction mediated by the SNS
What is the molecular mechanism of an erection?
- PNS releases: ACh, NO, and VIP that cause dilation in the cavernous smooth muscle
- NO activates guanylyl cyclase, causing an increase in cGMP
- cGMP decreases Ca++
- Decreased Ca++ leads to smooth muscle relaxation
*Note that cGMP is broken down by a phosphodiesterase
What is the mechanism of viagra?
Antagonism of the phosphdiesterase the breaksdown cGMP
