Male Sex Hormones Flashcards
1) Understand androgen biosynthesis and its intervention 2) Understand androgen receptor action and its intervention 3) Know the synthetic androgens and their uses 4) Know anti- androgens and their uses
Review: 2 main male sex hormones? What receptor do BOTH bind to?
T and DHT (65% of circulating hormone is bound to SHBG– 33% bound to albumin– i.e. there is very little FREE hormone around)
Both T and DHT bind to Androgen Receptors–> same TARGET- so can’t use that pharmacologically
What are the 2 adrenal androgens? Are these potent or weak? What do they co?
androstenedione
DHEA
Both are WEAK (compared to T and DHT)
- Thought to contribute to hair growth, bone maturation, and sense of well being (DHEA)
Do women have testosterone?
Yep. It’s just, on average, about 5% that found in men.
In fact.. they NEED to have some testosterone as it’s the building block for estrogen (aromatase converts testosterone–> estrogen in ADIPOSE and in the LIVER)
Review: What enzyme converts T to DHT? (She EMPHASIZED this)
5 alpha reductase.
Know this!
Where does T get converted to E2? How? (in men)
Liver and adipose, by aromatase.
Important: What is the co-activator of the androgen receptor (AR)? (She EMPHASIZED this…)
ARA 70
DHT and T won’t work without it.
AR- Ligand complex MUST bind it to exert complete activity
5 things that are more T’s domain (vs. DHT)?
1) Sex drive, performance
2) Muscle mass increase
3) Penile, scrotal growth
4) Voice deepening
5) Spermatogenesis
8 things that are more DHT’s domain (vs. T’s)?
1) Body and face hair
2) Acne
3) Male-pattern baldness
4) Prostate enlargement
5) Skeletal growth / epiphyseal closure
6) Stimulate lean body mass (what does this mean?)
7) Stimulate EPO and clotting factors
8) Decrease HDL
Do any partial agonists/antagonists exist for androgens?
Nope.
4 uses of therapeutic anabolic steroids?
1) Androgen replacement therapy -for hypogonadism/ hypopituitism (and aging males?).
2) Protein anabolic effects - for chronic diseases, e.g. AIDS wasting.
3) Anemia - but EPO does this much more specifically.
4) Athletic performance enhancement.
What’s the chemical structure feature to remember about drugs meant to help with cachexia to help gain lean mass (similar to testosterone)?
Esterification at the 17-beta position.
(she said this is important)
They are COMPLETE androgens–> used as drugs for severe anorexia
What’s the chemical structural feature notable for androgens that have more specific anabolic effects (increases RBC and muscle mass) ?
Alkylation at the 17alpha position.
(she said this is important)
These are the ones commonly abused!
Can be detected in plasma/urine
4 categories of bad things about anabolic steroids?
1) Inhibition of FSH/LH- messes up HPA axis
2) Spermatogenesis / menstrual cycle messed up.
3) Libido, liver, CV problems.
4) Secondary sex characteristics of opposite sex (feminization / verilization).
What drug inhibits 5alpha reductase? (She emphasized this…)
Finasteride.
PREVENTS the conversion of T to DHT.
Potential to reduce baldness/ BPH/
- Works REALLY well for BPH
- Not that well for male pattern baldness
What are the 2 isoforms of 5alpha reductase? Where is each more expressed (3 areas)?
Type II: high in prostate and hair follicles, low in sebaceous glands–> this is
Type I: high in sebaceous glands, low otherwise
