L16 Male Contraception Flashcards
What are the 3 parts of the male reproductive shown in class
testis, epididymis, vas deferens
Describe the inside of a testis
Comprised of seminiferous tubules and Leydig cells (surround the tubules)
What is the function of Leydig cells
they produce high local testosterone (5-7mg/day)
TF: Leydig cells are found inside the seminiferous tubules
False, Leydig cells are found outside the tubules, while Sertoli cells are found inside
What is the function of Sertoli cells
they embed and support maturing sperm cells
what is the daily sperm production in humans
34g
what is the sperm concentration in most fertile men
greater or equal to 15 million/ml (range of 15-200 million/ml)
What sperm concentration results in only 1% pregnancy risk
lesser or equal to 1 million/ml
How long is spermatogenesis for humans
64 days (2 months)
TF: Sertoli cells produce testosterone and estradiol
False
Which molecule serves as a building block for steroids
cholesterol
which hormone primarily regulates testosterone production
LH
TF: progesterone is a precursor for testosterone
True
Which chromosome is the human androgen receptor gene located on
X
TF: the ligand-binding domain for hAR (human androgen receptor) protein is at the NH2-terminal domain
False, its at the C terminal
The N-terminal domain = transcriptional activation
Describe the mechanism of action for androgen
- Testosterone and Dihydrotestosterone (DHT) enter the cell
- T is converted to DHT by 5alpha-reductases using NADPH
- DHT binds to androgen receptors along with coregulators to move into the nucleus
- Transcription is activated
Which enzyme converts T into estradiol?
aromatase
Which enzyme converts T into DHT?
5alpha-reductase
What does T act on? DHT? estradiol?
T: muscle, bone marrow, bone, brain
DHT: external genitalia, prostate, skin, hair
Estradiol: Bone, brain, breast
What behaviors are associated with low estrogen
increased sex drive and increased activity
What behavior(s) is/are associated with high estrogen
decreased eating
What behavior is associated with high DHT
increased eating
What does 5alpha-reductase do?
converts T into DHT
What does aromatase do?
It converts T into estradiol
TF: testosterone causes an individual to be calmer
False, it causes aggression
What are the 4 contraceptive methods for men
Male vasectomy, male condom, withdrawal, spermicide
TF: Most of the population relies on male contraceptives
False, only 40% of the population relies on male contraceptives
TF: Condoms are only used to prevent pregnancies
False, they are important to prevent STDs
How does male vasectomy work?
The vas defends is cut
What is vasovasotomy
It is the reverse process of male vasectomy
What are potential male contraceptive methods that are being developed
Hormonal (injections/implants/creams), non-hormonal, immunocontraception
What is the negative feedback mechanism operating in male gametogenesis
Testosterone and estradiol (leydig cells) + inhibit-B (sertoli cells)
*inhibin-B only acts at the level of the pituitary and primarily acts on FSH
TF: administering sustained doses of testosterone to rabbits for 3 months increases plasma testosterone
True
Does administering testosterone increase spermatogenesis? Why?
No, spermatogenesis is triggered by production of endogenous testosterone or local testosterone levels in the germ cells.
Increasing serum testosterone levels actually deters spermatogenesis since the body will stop producing testosterone
TF: Testosterone injection could potentially be used as a contraceptive method
True
How does testosterone affect LH and FSH production
Testosterone is a negative feedback regulator that acts on the hypothalamus and the anterior pituitary glands, signalling them to stop producing LH and FSH
Why is testosterone used in combination with estradiol to suppress spermatogenesis
Combining testosterone and estradiol aims to suppress sperm production effectively while minimizing the side effects associated with higher doses of testosterone alone. Estradiol is believed to enhance the contraceptive effect by further suppressing gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone (FSH) from the pituitary gland.
TF: Hormonal implants for men such as T-E implants are effective immediately
False, it takes 64 days (time for sperm to mature)
What are options for hormonal contraception for men other than exogenous testosterone administration
Exogenous Progesterone, GnRH antagonists
How do hormonal male contraceptives work? What is their aim?
To inhibit FSH and LH secretion/production
What is Dimethandrolone undecanote
Male hormonal contraceptive
Androgen and progesterone receptor agonist
Not aromatized I.e. no estrogen in activity/feminizing side effects
Not a substrate for 5alpha-reductase (which converts T to DHT)
What is 11beta-MNTDC
A male hormonal contraceptive that suppresses serum gonadotropins (LH and FSH)
What are some non-hormonal methods of contraception
Thermal contraceptives (hot baths, heating devices, heating underwear, silicone ring, ultrasound)
Drugs that cause azoospermia (prevents mitosis but non-selective, used in cancer, cytotoxic)
Gossypol, retinoids acid deprivation, BRDT inhibition, spin inhibition, inhibition of soluble adenyl Cyclades (sAC)
What is gossypol?
Non hormonal male contraceptive, daily pill that suppresses sperm production, permanent/irreversible in 10-20% of men
Cotton seed oil extract
What is an important consideration when targeting retinoic acid for spermatogenesis inhibition
Retinoic acid inhibitors like WIN 18,446 induce a disinformation/disinhibition reaction in men who drink alcohol
It blocks the action of an alcohol metabolizing enzyme
How does BRDT (a bromodomanin protein) work
BRDT is required for meiosis
Current inhibitor JQ1 also inhibits other bromodomanin proteins leading to toxicity
Completely reversible
Why is the epididymis a target for male contraception? What are some examples
It is involved in the maturation process for the sperm
It is perhaps reversible
Steroid 5alpha-reductive inhibitors
Calcium channel blocker (prevents enzyme action needed for fertilization - not specific)
Sperm mobility as a target (mifepristone)
What is eppin
Human sperm surface protein, important for sperm motility
What are the advantages of inhibiting soluble adenyl cyclase (sAC)
It is specific and reversible (targets sperm motility)
What are the general trends for testosterone concentrations throughout male life span
Lowers with age
Increases during puberty
Increased during fetal and neo-natal development as well
Minimum during pre-pubertal (near zero)
What are symptoms associated with T deficiency (4)
Sexual dysfunction (decreased libido, erectile dysfunction)
Adverse metabolic effects (CRA, coronary artery disease)
Decreased bone density
Potentially affects cognitive function
Hormonal replacement therapy benefits include:
Preserve/improve bone mass, muscle mass, strength, physical functions, libido, well-being, mood, cognition
Why is hormonal replacement therapy for men only useful in cases of androgen deficiency
There are adverse affects since the hormones target many cells throughout the body
What are three examples of androgen abuse
Rejuvenation, sports, body building
What are potential negative side effects to androgen abuse
Inhibition of spermatogenesis
Feminization since T can be hydrolyzed into estrogen (specifically estradiol) by aromatase
*aromatase is usually found in granulosa cells and Sertoli cells
