Male Sex Hormones Flashcards
What is the most potent androgen?
5alpha-DHT
How potent is testosterone?
Moderately
What is the least potent androgen?
DHEA
At what age does plasma testosterone start to decline?
50
What enzyme converts testosterone to DHT?
5alpha-reductase
What % testosterone is unbound?
2%
What % testosterone is bound to SHBG?
65%
What % testosterone bound to albumin
33%
Where is testosterone converted to DHT?
Target tissues, not the blood since most is bound
Where is testosterone converted to estrodiol?
Adipose and liver
What enzyme converts testosterone to estrodiol?
Aromatase
What hormones bind to androgen receptor?
Testosterone and DHT
What is the co-activator of androgen receptor?
ARA70, must bind to receptor complex for androgen receptor to function
What are the physiological effects of testosterone?
- Male sex drive and performance
- Muscle mass inc
- Penile and scrotal growth
- Vocal cord thickening
- Spermatogenesis
What are the physiological effects of DHT?
- Inc facial and body hair
- Acne
- Scalp hair recession
- Prostate enlargement
- Skeletal growth and epiphyseal closure
- Stimulate lean body mass
- Stimulate erythropoietin and clotting factor production
- Dec HDL
Are the effects of testosterone and DHT general or tissue specific?
Tissue specific
What are some therapeutic uses of synthetic androgens?
- Androgen replacement therapy for hypogonadism or aging males
- Protein anabolic effects for catabolic disorders
- Anemia via EPO
- Anabolic steroids in athletes
What are synthetic androgens?
Full androgen agonists can be esterified or alkylated
Potency of esterified synthetic androgens?
Similar to testosterone
Potency of alkylated synthetic androgens?
more pronounced anabolic properties so they are more specific for things like catabolic disorders
What are the risks in male athletes associated with anabolic steroids?
- Inhibit LH/FSH
- Withdrawal=infertility (azoospermia)
- Loss of libido/impotence
- Feminization (T–>E)
- Liver toxicity
- CV toxicity
What are the benefits in male and female athletes associated with anabolic steroids?
-Anabolic and EPO effects
What are the risks in female athletes associated with anabolic steroids?
- Inhibit LH/FSH
- Menstruation effects
- Anovular cycles/infertility
- Loss of libido
- Virilization
- Liver tox
- CV tox
What is a drug used for synthesis inhibition/anti-androgen therapy?
Finasteride
What is the MOA of Finesteride?
Competitive inhibition of 5alpha-reductase type II–>blocks DHT formation in prostate gland, reducing serum DHT levels by 70%
What are the two 5alpha-reductase isoforms and where are they located?
Type I
-low expression in prostate, hair follicles. High in sebaceous glands (acne) and is only weakly inhibited by finasteride
Type II
-High expression in prostate, hair follicles, low in sebaceous glands, potently inhibited by finasteride
What is finasteride approved for?
- Benign prostatic hyperplasia (BPH)–>dec prostate volume because prostate enlargement is dependent on DHT formation via type II
- Male pattern baldness: bald men have more DHT in hair follicles.
What is an example of an androgen receptor antagonist?
Flutamide
What is the MOA of flutamide?
Pure androgen receptor antagonist (prevents ARA70 binding?)
What are the therapeutic uses of flutamide?
- Hormone sensitive prostate cancer. Block DHT binding, reduce gene transcription and androgen effects on tumor growth
- Precocious puberty
- Female virilization (dev of male characteristics)
