What are the two metabolic products of testosterone?
Dihydrotestosterone and estradiol
The production of sperm and testosterone in the testes is regulated by what part of the brain?
The hypothalamic-pituitary-testicular axis
What does the epididymis connect?
Rete testis and vas deferens
What keeps sperm in an inactive state in the epididymis?
The cells of the epididymis secrete H+ to acidify the luminal fluid, which keeps sperm in an inactive state
The vas deferens connects what two places?
epididymis and the seminal vesicles
What is the enlarged space located at the juncture between the vas deferens and the seminal vesicles, and what is its function?
the ampulla Store sperm
What is the path of travel of sperm from the seminiferous tubules to the urethra? (7, starting at and including the seminiferous tubules)
Seminiferous tubules Rete testes Epididymis Vas Deferens Ampulla Ejaculatory duct Urethra
Where are aging sperm reabsorbed?
Where are sperm stored?
What are the two erectile tissues in the penis?
1 x Corpus spongiosum 2x Corpus cavernosum
What part of the male genitalia produces the largest portion of semen?
Seminal vesicles (60%)
What is in seminal fluid that provides energy for sperm?
What is in seminal fluid that causes the cervical environment to be more favorable for sperm survival and promotes peristalsis in the uterus and fallopian tubes?
What is in seminal fluid that causes semen to coagulate after ejaculation? Why is coagulation important?
Fibrinogen Aids in holding the semen in deeper regions of the vagina, closer to the cervix
What attaches to sperm and serves to suppress motility of sperm in the coagulated semen?
What is the main function of the prostate?
Secretes fluid for semen
Prostatic fluid constitutes approx. what % of the volume of semen?
What is the function of prostatic acid phosphatase that the prostate secretes?
What is the function of profibrinolysin (Plasminogen) that the prostate secretes?
dissolves coagulated semen
What is the function of the HCO3 that the prostate secretes?
Neutralizes acidic environment of the cervix
What is the function of PSA that the prostate secretes?
PSA hydrolyzes seminogelin, which increases sperm motility.
The prostate is an androgen sensitive tissue. Over 90% of testosterone that enters prostatic cells is converted to what? What does this do?
dihydrotestosterone (DHT) by 5α-reductase. DHT is the primary regulator of prostatic growth
What is the function of the bulbourethral glands?
Secretes mucus into the urethra upon arousal
What is the function of the ampulla?
Hold sperm Contracts to propel sperm
What are the three accessory glands of the male reproductive system?
Seminal vesicle Prostate Cowper glands
What are the three different portions of the epididymis?
Cauda Corpus Caput
In what third of the epididymis are sperm most mature?
What are the cells in the testes that produce testosterone from cholesterol?
Cells of Leydig
Where are the leydig cells located?
In the peritubular compartment of the testes
Where are the sertoli cells located?
in the intratubular compartment
What are the functions of the sertoli cells? (3)
Provide environment for germ cells to develop Stem cell niche Produce and secrete androgen
Is spermatogenesis synchronous or asynchronous?
GnRH is secreted in a pulsatile fashion. What controls the frequency of these pulsations?
Pulse generator of the Hypothalamus
What are the steps of the hypothalamic-pituitary-gonadal axis?
1. GnRH secreted to pituitary gonadotrophs, which secrete LH and FSH
What is the path of LH production?
Sent to Leydig cells, where they increase testosterone synthesis
What is the path of FSH?
Go to sertoli cells, to produce ABP
What hormone controls sertoli cell proliferation and seminiferous tubule growth?
Why is it important to have a pulsatile secretion of GnRH?
Desensitization of the gonadotroph cells
Once LH is secreted into the circulation, it travels to the testes and binds to what?
G protein-coupled receptors on Leydig cells
Activation of LH receptors increases what? What does this lead to?
Activation of LH receptors increases intracellular cAMP levels, which leads to an increase in the synthesis of steroidogenic enzymes that control the production of testosterone
Where is the testes are the blood vessels, macrophages, CT etc: the peritubular space, or the intratubular
What are the cells that produce the androgen binding protein, and what are they signalled by?
Sertoli cell, receive signal via FSH from pituitary gonadotropes
How does LH increase the production of testosterone from the Leydig cells?
increasing the expression of cholesterol side chain cleavage enzyme, thereby, increasing conversion of cholesterol into pregnenolone
How does testosterone increase sperm synthesis?
diffuses into sertoli cells
What is the feedback mechanism for testosterone?
directly inhibits the secretion of both LH and FSH from the pituitary gonadotropes
How does testosterone inhibit the secretion of LH? (2)
Can change to DHT and E2, and inhibitsecretion of GnRH and LH from the hypothalamus and pituitary gland, respectively.
How does FSH exert its effects on the sertoli cells?
Inducing the synthesis and secretion of androgen binding protein (ABP) by the Sertoli cells
How does ABP facilitate spermatogenesis?
by concentrating testosterone at the site of spermatogenesis
The testosterone concentration is 100-fold greater the area surrounding the developing sperm than in the blood stream. What allows for this wicked increase?
Androgen binding protein
How do Sertoli cells inhibit the production of FSH?
Produce inhibin, which can travel in the blood stream to the anterior pituitary, where it selectively inhibits FSH production.
What are the two, broad categories of androgen effects?
1. Androgenic functions 2. Metabolic functions
What are the androgenic functions of testosterone?
actions on the male reproductive tract and main secondary male sexual characteristics
What are the metabolic functions of testosterone?
actions on the nonreproductive tissues such as muscle, bone, bone marrow, kidney, and liver
What is inhibin produced by, and what does it act on to inhibit FSH secretion?
Produced by sertoli cells, and inhibits Pituitary gonadotrops
GnRH agonists are used to reduce androgen synthesis in prostate CA. What is the MOA behind this?
Causes desensitization in the gonadotrophs in the pituitary,
LH binds to what type of G protein on Leydig cells? (Gs, Gi, or Gq)?
When testosterone diffuses from the Leydig cells into the sertoli cells, it is acted upon by what enzyme? What does this produce?
Aromatase, producing estradiol
Draw out the cholesterol synthesis pathway.
What is the rate limiting step of the testosterone synthesis pathway? (include substrate, enzyme and product)
Cholesterol to pregnenolone via cholesterol desmolase
LH increases the expression of which enzyme in the testosterone synthesis pathway?
Cholesterol desmolase (also called cholesterol desmolase or P450scc)
What is the enzyme found in places such as the prostate, that converts testosterone into the more potent hormone dihydroxytestosterone (DHT)?
What is the enzyme that converts testosterone into estradiol in places like the brain, adipose tissue, testes, and liver?
What are the two ways in which LH regulates the production of testosterone?
1. Expression of cholesterol desmolase 2. Increases the rate of transport of cholesterol into the mitochondria
When do the first two spikes of testosterone occur in a male?
fetal, and neofetal
What causes testosterone to fluctuate throughout the day?
The pulsatile nature of GnRH
What are the two major proteins in the blood stream that binds to testosterone?
sex hormone binding globulin (SHBG) and albumin (40/60 split)
Is testosterone that is bound to albumin available to a cell? How about if bound to SHBG?
Available only if bound to albumin, NOT SHBG
What are the two factors that decrease the circulating amount of testosterone in the blood as men age?
Decreased synthesis Increased SHBG
Testosterone freely crosses the cell membrane and into the cell because of its lipophilicity. Once in the cell, what does it do/bind to? Where is this?
Binds to androgen receptor in the cytoplasm. This complex can then go into the nucleus, and increase transcription
What is the enzyme found in the cytoplasm of cells that converts testosterone to estradiol?
What is the relative binding affinity of DHT for the androgen receptor protein compared to testosterone?
DHT have much higher affinity
What are the two main androgens produced in the adrenal glands?
Androstenedione and DHEA
Androstenedione and DHEA are not very potent hormones relative to testosterone, but they can be converted to testosterone in some tissues. What is the enzyme that does this?
What are the three main effects of testosterone?
1. Internal genitalia 2. Increases muscle 3. Erythropoiesis
What are the two main effects of DHT?
Do stuff to external genitalia Increase hair follicles
What is the main effect of estradiol?
What are the two main metabolic effects of testosterone?
1. Increases metabolic rate 2. Inhibits lipid accumulation
How are the spermatogonia developed in the male fetus?
Primordial germ cells migrate to the basal compartment of the testes and line the seminiferous tubules
What is the immunoprivileged site in the testes? What prevents the immune system from entering?
between the Sertoli cells--adluminal compartment of the seminiferous tubule Tight junction between sertoli cells
What happens to spermatogonia as they migrate up the sides of the Sertoli cells in the space between them, towards the seminiferous tubule?
Maturation to spermatocytes
What are the maturation stages of spermatogonia to sperm?
1. Spermatogonia 2. Primary spermatocytes 3. Secondary spermatocytes 4. Spermatids
What is spermiogenesis?
WHen spermatids gain flagella and mature to sperm
What is spermiation?
Release of spermatids into the seminiferous tubules
What are the two main hormones that act to produce sperm?
1. Testosterone 2. FSH
What are the two roles that testosterone plays in the development of sperm?
1. Stimulates transcription of genes in sertoli cells 2. Converted to estradiol
What are the three roles of FSH in spermatogenesis?
1. Increase ABP 2. Increases aromatase 3. Stimulates growth factors in Sertoli cells
Why can anabolic steroid administration reduce spermatogenesis?
Feedback to inhibit LH and FSH production **Loss of FSH** despite presence of testosterone
What hormone is the main regulator of spermatogenesis?
What is the first step of spermiogenesis?
Golgi buds off acrosomal vesicle
What is the next step in spermatogenesis after the Golgi produces the acrosomal vesicle?
Acrosomal vesicle moves to one pole of the elongating nucleus forming the acrosomal cap
What is the next step in spermatogenesis after the acrosomal vesicle moves to one pole of the elongating nucleus forming the acrosomal cap?
Centrioles migrate to the end of opposite to the cap and form the flagellum.
What is the next step in spermatogenesis after the centrioles migrate to the end of opposite to the cap and form the flagellum?
What is the next step in spermiogenesis after the flagella elongates?
Mitochondria migrate to the tail end of the sperm
What is the next step in spermiogenesis after the mitochondria migrate to the flagellar end of the sperm?
Sertoli cells phagocytose excess cytoplasm
What is the function of the blood testes barrier beside immunoprivilege?
Maintenance of fluid composition
What does hypergonadism lead to?
What are the two tumor causes of hypergonadism?
Hypotahalmic or androgen producing tumors
What are the two non-tumor causes of Hypergonadism?
LH receptor mutations Congenital adrenal hyperplasia
What, generally, is hypogonadism?
What is the cause of primary hypogonadism? Why is there higher levels of FSH and LH?
Testicular dysfunction leads to a decrease in testosterone production (hypergonadotropic hypogonadism) Higher levels d/t lack of feedback via testosterone
What are the two disease processes discussed in class that lead to primary hypogonadism?
Cryptorchidism Klinefelter syndrome (XXY)
What is secondary hypogonadism?
Decrease in circulating gonadotropins (hypotrophic hypogonadism)
hypergonadotropic hypogonadism = ? Hypogonadotropic hypogonadism = ? (primary vs secondary)
hypergonadotropic hypogonadism = primary Hypogonadotropic hypogonadism = Secondary
What is Kallmann syndrome? MOA?
Secondary hypogonadotropic hypogonadism inherited malfunction of GnRH neurons
Parasympathetic or sympathetic: male erection?
Parasympathetic or sympathetic: luberication?
Parasympathetic or sympathetic: emission?
What lubricates the urethra?
Bulbourethral glands secrete mucus
What happens during the emission stage of male sexual arousal? (3)
1. Ampulla contracts 2. Seminal vesicles contract 3. Bladder sphincter contracts
What is the mechanism behind an erection?
Vasodilation, sinusoidal spaces fill with blood, and compress veins
What causes the vasodilation in an erection? (3 chemicals)
Parasympathetic nerve terminals release acetylcholine, nitric oxide (NO), and vasoactive intestinal peptide (VIP).
What is the effect of Ach in an erection?
Triggers NO release
What is the MOA of NO?
INduces G protein and cGMP, causing relaxation of smooth muscles of arterioles
What terminates an erection?
Sympathetic nerve activity which promotes arterial constriction
What is the MOA of viagra?
Inhibits the phosphodiesterase the degrades cGMP