lect 15 male contraceptive Flashcards
sperm is generated from where
reproductive stem cells in testis specifically in seminiferous tubules
pathway of sperm
testis–>epididymis–>Vas Deferens–>urethra
place where sperm matures how and why
epididymis to acquire the ability to fertilize an oocyte. Sperm must differentiate and reduce size of its genetic material and develop a propulsion system
process where diploid stem cells spermatogonia become haploid spermatozoa and days that it takes place
spermatogenesis and 64 days
spermatozoa lack what
LH and FSH receptors
cells found outside the seminiferous tubule
leydig cells
LH acts on what and triggers what
Lh receptors of leydig cells and triggers testosterone synthesis
production of local testosterone is important for what maturation
germ cell production and maturation of germ cells into spermatozoa
testosterone release causes what feedback
feedback inhibition of LH AND GnRH
testosterone is also transported where
sertoli cells
concentration of testosterone in seminiferous tubules vs circulation
10 times higher
cells found inside seminiferous tubules
sertoli cells
mother cells of germ cells in men
sertoli cells
what acts on sertoli cells
FSH in the fsh receptors
synthesis of testosterone
cholesterol side chain cleaved by enzyme. cholesterol than modifies into pregnenolone until into testosterone
testosterone can be further metabolized into whaat
dihydrotestosterone DHT and estradiol
enzyme to make DHT and modification
5a reductase. reduction of a double bond
affinity of DHT on androgen receptors
higher affinity for androgen receptors than testosterone
estradiol use in men
production of estrogen in testis
human androgen receptor on which chromosome
X chromosome
what happens to androgen receptor upon ligand binding
receptor dimerizes upon ligand binding and interacts with androgen response elements in genome to turn on synthesis of genes that are androgen dependent
the presence of 5a reductase and aromatase in local tissues allows for what
differential expression in tissues
steroid pyramid
cholesterol>progestins>androgens>estrogens
testosterone target what organs mainly
mainly muscle, bone marrow, bone, brain
DHT target organs (4)
external genitilia, prostate, skin and hair
stimulation of hair growth requires block of what enzyme
5a reductase
estradiol target organs (3)
bone, brain, breast
most direct way we can block sperm release
block vas deferens
methods of male contraceptive (4)
condoms, vasectomy, withdrawal, hormonal
hormonal contraceptive men
block cycle to prevent local testosterone for sperm production
concentration of testosterone for spermatogenesis compared to concentration required to maintain male features
10 times higher for spermatogenesis
testosterone administration contraceptive method and what is the goal
administrating exogenous testosterone for negative feedback, inhibiting local testosterone synthesis
administrating right amount of testosterone to enable feedback inhibition without inducing spermatogenesis
goal: block hypothalamic-pituitary axis to control testosterone levels
what do we get from sustained dose of testosterone in rabbits expriment and what happens if we increase that dose
we blocked the feedback and turned of leydig cells.
middle of graph we see axis has been turned off and no germ cells at that specific concentration of exogenous circulating testosterone. plasma testosterone measure is the one from the implant.
as we keep increasing implant dose, we eventually get enough testosterone to maintain spermatogenesis
problems with testosterone administration method
in species like rats and mokeys, there is less predictability in when do we get no sperm production.
too much heterogeneity.
difficult to calibrate the dose to get the right one
what are PDS implants
combination of testosterone and estradiol that can completely shut off spermatogenesis by feedback inhibition.
estradiol is more potent in inhibiting sperm production by feedback inhibition.
results of PDS implants
serum LH undetectable, spermatids much lowered. hormones levels not changed so no change in secondary sex characteristics
problems with PDS method
hard to calibrate. takes 3 months to wipe out spermatogenesis in humans. in rats it takes 57 days
testosterone and progestin hormonal method: androgen analog that is an androgen and progesterone receptor agonist
dimethandrolone undecanoate
characteristics of dimethandrolone undecanoate benefits
not aromatized so no estrogenic activity
not a substrate for 5a-reductase.
reduce side effects seen in previous therapies like that of estrogen
suppresses LH and FSh
testosterone analog that suppresses serum gonadotropins so cant act on leydig cells and sertoli
11beta-MNTDC
name for no sperm production by drugs
azoospermia like cancer drugs
control of meiosis method by control of retinoic acid effect on sperm
if we make retinoic acid is absent either from diet or chemically at certain stages of sperm development, we can block spermatogenesis, no germ cell production but be specific to testis because other tissues need retinoic acid.
retinoic acid important for sperm maturation
drug inhibiting what enzyme in testis and liver for retinoic acid synthesis
consequence it had on mice
WIN 18,4666 inhibits enzyme ALDH1A
in mice only have undifferentiated spermatogonia and no germ cells
cotton seed oil extract that suppresses sperm production and it side effects
gossypol. irreversible in some man and hypokalemic effect (high potassium levels)
sperm chromatin contraceptive method
dna is six fold more compacted in sperm than somatic cells. altering 3d structure dna of sperm may alter its swim capacity
drug targeting bromodomain containing proteins in sperm chromatin contraceptive method and what was the problem
JQ1
bromodomain containing proteins thought to be germ cell specific but is not
inhibition of fertilizing ability contraceptive method
inhibiting maturation and fertilization ability of sperm in epididymis since it only takes 7-10 days compared to germ cells taking 2 months to become sperm
immunocontraception method and problem
men have blood-testis barrier in testis to protect it so many things cannot get in.
Developing antibodies to sperm proteins, epididymal proteins and germ cells but method not reversible
serum testosterone concentration throughout lifespan
high in fetal (for male patterning and development of specific processes and tissues)
High in neonatal (to modify sex specific features)
large increase in puberty/adult.
low pre puberty
pulsatile concentrations of testosterone during which period
puberty and adulthood
drug methods for men when decreasing testosterone levels (4) called androgen therapy
testosterone, DHEA, Melatonin, human growth hormone
does androgen replacement therapy make men more fertile
NO, we see reduced sperm count
athletes using androgens for what and consequences
increase bone mass and growth but likely become sterile
estrogen levels affect what and how can we inhibit it
eating, copulation, and activity
block aromatase
DHT levels affect what habit
eating
what is linked to the temporary aggressiveness seen in adolescents
pulsatile changes in testosterone concentrations
gradual decrease of testosterone over the age of 30 leads to consequences in what
libido, muscles, activity
administrating testosterone in old men is only useful in what and administered how
androgen deficiency
administered as injection, patch, solution, or roll on
androgen replacement therapy benefits (4)
- improve bone mass
- increase muscle mass and strength
- increase libido
- improve well being and mood
androgen replacement therapy negative effects (alot)
1.Headaches
2.Baldness
3.strokes blood clots
4. High blood pressure
7. aggressive behaviour
10. severe acne
11. development of breasts
12. liver damage
13. enlarged prostate
14. shrinkage of testicles
nausea
bloating
reduced sperm count
