Lecture 16: Pharmacology of Male Sex Hormones, The Androgens

Question 1

What is 5 alpha reductase?

Answer 1

Reduces testosterone to 5-DHT

Question 2

Reduces testosterone to 5-DHT

Answer 2

1. Testosterone
2. DHT
3. Androstendione
4. Dehydroepiandosterone (DHEA)

Question 3

Where do the potent androgens come from?

Answer 3

Testis

- testosterone
- DHT

Question 4

Where do the WEAK androgens come from?

Answer 4

Adrenal, zona reticularis

- androstenedione
- dehydoepiandosterone (DHEA)

Question 5

What are the role of androgens?

Answer 5

Contribute to male pubertal changes
Hair growth
Bone maturation

Question 6

What does 3Beta HSD stand for?

Answer 6

HydroxySteroidDehydrogenase

Question 7

Where does testosterone convert to estradiol?

Answer 7

Adipose tissue
Liver
This is accomplished by AROMATASE

Question 8

Where does testosterone get converted to DHT?

Answer 8

In all tissues except for adipose and liver lol

Converstion done by 5(alpha) reductase

Question 9

What effects does testosterone bring about?

Answer 9

1. Male sex drive, performance
2. Muscle mass increase
3. Penile and scrotal growth
4. Vocal cord thickening
5. Spermatogenesis

Question 10

What effects does 5alpha-dihydrotestosterone (5-DHT) induce?

Answer 10

1. Stimulates EPO and clotting factor production
2. Stimulate lean body mass
3. Skeletal growth and epiphyseal closure
4. Prostate enlargement
5. Scalp hair recession
6. Acne
7. Increased facial and body hair
8. Decrease HDL – cholesterol levels

Question 11

What is ARA70? Significance?

Answer 11

A co-activator fo the androgen ligand complex
Absence of ARA-70 means that testosterone and DHT will have weak effect
Both AR-testosterone and AR-DHT complexes bind to ARA70

Question 12

What happens if ARA70 is not present?

Answer 12

The activity of testosterone and DHT in activating gene transcription is markedly diminished

Question 13

What is significant about the fact that DHT and testosterone share a receptor?

Answer 13

It means if you want to have one effect over the other (i.e. you want EPO from DHT but you don’t want acne, how do you do this?)

Question 14

What is androgen therapy?

Answer 14

Receptor agonists

Question 15

What is anti-androgen therapy?

Answer 15

Receptor antagonists
Synthesis inhibitors (inhibitors of 5alpha reductase)

Question 16

Do we have mixed agonist/antagonist for androgens?

Answer 16

NO

Question 17

What are synthetic androgens used for?

Answer 17

1. Androgen replacement therapy
   
   • hypogonadism
   • aging males
2. Protein anabolic effects
   
   • post surgical states, chemotherapy recuperation
3. Anemia
4. Anabolic steroids in athletics

Question 18

What is the difference between the 17 alpha and 17 beta position on androgens? Significance?

Answer 18

Differences in which way –OH pointing

-Significance is that the different positions have different functions

Question 19

What is the function of 17alpha testosterone?

Answer 19

Increase Red cell mass
Increase muscle mass
e.g. Methyltestosterone, Fluoxymestrone, Stanozol, Nandrolone, Oxandrolone

Question 20

What is the function of 17beta testosterone?

Answer 20

Comparable potency to testosterone

Question 21

What are the two types of 5alpha reductase? Significance?

Answer 21

Type 1
-basic
-5p15, SRD5A1 gene
-low expression in prostate, hair follicles
-expression in sebaceous gland is HIGH
Type 2
-acidic
-low expression in sebaceous gland
-high expression in prostate, hair follicles
You want to target the Type 2 5a-reductase

Question 22

What is the drug used to target BPH?

Answer 22

Type II 5a reductase inhibitor
Because Type 2 converts testosterone to DHT in prostate specifically
Drug = Finasteride

Question 23

What is the benefit of anabolic steroids in men/women?

Answer 23

1. Anabolic effects

2. EPO effects

Question 24

What are the drugs used to treat prostate cancer?

Answer 24

1. Finasteride

2. Flutamide

Question 25

What are the disadvantages of anabolic steroids in men?

Answer 25

1. Long term inhibition of LH/FSH 2. Withdrawal leads to reduction in T so AZOOspermia 3. loss of libido and impotence 4. Feminization (T is converted to E) 5. Liver toxicity 6. CV toxicity

Question 26

What are disadvantages of anabolic steroids in women?

Answer 26

1. Inhibition of LH/FSH 2. Anovular cycles/infertility 3. loss of libido 4. virilization 5. liver and CV toxicity

Question 27

What are the types of synthesis inhibition drugs?

Answer 27

1. 5a –reductase inhibition | e. g. Finasteride

Question 28

What is Finasteride?

Answer 28

Inhibits Type II 5a-reductase Inhibits the synthesis of androgen Used to reverse prostatic enlargement Used to treat baldness because Type II predominates in hair follicles

Question 29

What drug targets Type II 5a reductase?

Answer 29

Finasteride

Question 30

What are the types of receptor antagonists?

Answer 30

1. Flutamide 2. Cyproterone 3. Spironolactone

Question 31

How do you treat prostatic cancer?

Answer 31

1. LH-RH agonists - Goserelin, Leuprolide 2. Receptor antagonists - Flutamide, nilutamide

Question 32

What is the MoA of Flutamide and receptor antagonists of androgens in general?

Answer 32

Inhibits ARA70

Question 33

How are the effects of T and DHT determined?

Answer 33

The effects of testosterone and 5(alpha)-DHT are tissue SPECIFIC

Question 34

How do you treat hypogonadism/pituitarism?

Answer 34

Androgen treatment consists of administering synthetic androgens (receptor agonists) to treat of hypogonadism or hypopituitarism

Question 35

What are LHRH agonists?

Answer 35

Luteinizing hormone-releasing hormone