Male Reproductive Physiology and Pharmacology Flashcards
WHere does spermatogenesis happen?
in the seminiferous tubules of the testicles
Where in the tubule are the spermatogonia located?
closest to the basement membrane - they move further in as they develop with spermatozoa at the very inner portion
SPermatogenesis is staggered throughout the seminiferous tubules sot hat all developmental phases are present at any one time. What is a spermatogenic wave?
defined as the time (distace) it takes for the reappearance of the same stage within a given segment of the seminiferous tubule
Why is this important?
it ensures that spermatozoa are produced continuously so that mature speram are always available for when the male finds a ready female
Because of spermatogenic waves, drug or environmental conditions that affect spermatogenesis may be measureable for how long?
up to 2 months post insult
What is the average daily sperm production?
about 100 million
Spermatogenesis is positively correlated with what hormone?
testosterone levels
How long does it take for the mitosis stage?
16 days
How long doe sit take for the first meiosis?
24 days
How long does it take for the second meiosis
only a few hours
How long does spermiogenesis take?
24 days
What does GnRH trigger in the males
anterior pit release of FSH and LH
What does FSH and LH do in the male?
make testis produce testosterone
Testosterone has negative feedback at what levels?
both hypothalamus and anterior pituitary
What cell does the LH bind to in the male?
leydig cell
What does this promote?
production of testosterone
What does the FSH bind to in the male?
sertoli cells
What does this trigger?
- makes androgen binding protein to increase concentratin of testosterone
- production of inhibin
WHat do the sertoli cells do for the developing sperm?
- protects them from plasma
- nrouishes them
- secretes luminal fluid and provides androgen binding protein
- secretes paracrine agents that stimulate sperm proliferation and differentiation
- make inhibin
- paracrine signals to leydigs
- phagocytize defective sperm
- secrete mullerian inhibitin substance
Low sertoli cells numbers are associated with….
low spermatogenesis
Low leydig cell numbers are correlated with what hormone levels?
decreased testosterone levels
increased gonadotropin levels (lack of negative feedback)
WHat are some symptoms of decreased testosterone (andropause)?
decrease in testicular function
erectile dysfunction
weight gain
gynecomastia
How do we diagnose androgen deficiency?
total testosterone level
may follow up with FSH/LH
What are the treatment optoins for androgen deficiency?
hormone replacement
sleep, eat, exercise
viagaral for ED
WHat are the thre emain natural androgens?
androstenedione
testosterone
dihydrotestosterone
What tissues will be affected by targeting testosterone?
muscle
seminal vesicle
epididymis
boen
What tissues will be affected by the 5alpha reductase inhibitors?
prostate
external genitalia
skin - hair pattern
Where is most of the testosterone in the male produced?
95% in leydig cells
5% in adrenals
What is the most potent of the natural testosterone?
dihydrotestosterone
Gemales have 20x less androgen than males, but where are they made?
adrenals and ovaries
What will bind the androgens and estrogens and 19-nor progestins?
sex hormone binding lbogulin
Where else is sex hormoen binding globulin made besides sertoli cells?
liver
The androgen receptor binds all androgens and belongs to what family?
steroid receptor superfamily - acts as a transcription factor
What will convert testosterone to DHT?
5alpha reductase
What are the anabolic effects of androgens?
muscle building - positive nitrogen balance, increase in protein synthesis
bone growth and closure of epiphysis
sodium and water retention (similar to estrogen)
What are the testosterone preparations?
oral pellets transdermal patch gel transbuccal
What is the main Testosterone analog?
methyl testosterone
Where is the methyl substitution t make it orally actie?
7-17
What are the side effects of methyl testosterone?
hepatotoxicity
acute cholecytstitic
What is the DHT derivatige?
oxandrolone
Which one is more used for testosterone hormoen replacement and which is the anabolic steroid
methyl testosterons it eh HRT
osandrolone is the anabolic steroid
What are the adverse effect sof androgen therapy?
- growth interruption in growing youth (premature bone closure)
- priapism
- sodium and water retention
- jaundice
- hepatic carcioma
- hypogonadism (long term cessation of HPO axis)
- aggressive behavior
- urinary obstruction - due to prostate growth
gynecomastia, testicular shrinkage, baldness
Why so many side effects?
Studies have shown that androgen-anabolic steroids bind to glucocorticoid, progesterone, and estrogen receptors and exert multiple effects
What are the purposes for medical castration?
to interfere with precocious puberty
- to treat androgen dependent cancers
- reduce libido
What are the three options for medical castration?
- androgen receptor antagonists
- nonpulsatile GnRH agonists
- nonpulsatile GnRH antagonists
What is intracrinology?
local formation of sex steroids
important in postmenopausal women where all estrogesna nd androgens are made locally in peripheral target tissues
Why is intracrinology important in treating disease?
if the goal is to shut down the hypothalamic pituitary gonadal axis, the GnRH agonists and antagonists are fine
but if the goal is to reduce androgen receptor signaling in a peripheral tissue like the prostate gland, you need to use an androgen receptor antagonist and/or 5 alpha reductase inhibitor
What is cyproterone acetate?
androgen antagonist
What is cyproterone acetate used for?
- reduce excessive sexual drive in men
2. trea thirsutism in women with combo of estrogen
What are the nonsteroidal pure receptor androgen antagonist?
Flutamide, Bicalutamide, Nilutamide
What are the flutamides used for?
advanced prostate cancer
What are the side effect sof the flutamides?
gynecomastia, hepatotoxicity
What is spinoloactone
it’s a weak androgen antagonist
What is spironolactone used for?
hirsutism and acne in women
diuretic is the main use
in some OCP
What is the hu,an recombinant GnRH agonist?
gonadorelin
What do we use gonadorelin for?
- used for functional assessment of the gonadal response
2. male infertility - give pulsatile
What is the main synthetic GnRH agonist?
leuprolide
What is leuprolide used for?
castration for cancer treatment - continuous sabdministration causes hypersection of LH and FSH first, but then suppression
uterine fibrois
ovarian stimulation with pulsatile administration
also gonadotropin dependent precocious puberty
What are the two GnRH antagonists?
Degarelix
Ganirelix and Cetrorelix
What is the main 5 alpha reductase inhibitor?
finasteride
also Dutasteride
What is finasteride used for?
BPH
male pattern baldness
What additional things can dutasteride be used for?
hirsutism in women in combo with anti-androgens
How does sildenafil work?
inhibits phosphodiesterase 5, so you don’t get the breakdown of cAMP and the vasculature in the penis doesn’t regain tone - keeps erection going
What shouldn’t you use the PDE-5 inhibitors with?
nitrates or beta blockers
What are the syde effects if PDE-5 inhibitors?
headache, flushig , dyspepsia and nasal congestion
