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Reproduction Week 2 > Lecture 16: Pharmacology of Male Sex Hormones, The Androgens > Flashcards

Lecture 16: Pharmacology of Male Sex Hormones, The Androgens Flashcards

1
Q

What is 5 alpha reductase?

A

Reduces testosterone to 5-DHT

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2
Q

Reduces testosterone to 5-DHT

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

Where do the potent androgens come from?

A

Testis

- testosterone
- DHT
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4
Q

Where do the WEAK androgens come from?

A

Adrenal, zona reticularis

- androstenedione
- dehydoepiandosterone (DHEA)
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5
Q

What are the role of androgens?

A

Contribute to male pubertal changes
Hair growth
Bone maturation

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6
Q

What does 3Beta HSD stand for?

A

HydroxySteroidDehydrogenase

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7
Q

Where does testosterone convert to estradiol?

A

Adipose tissue
Liver
This is accomplished by AROMATASE

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8
Q

Where does testosterone get converted to DHT?

A

In all tissues except for adipose and liver lol

Converstion done by 5(alpha) reductase

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9
Q

What effects does testosterone bring about?

A
  1. Male sex drive, performance
  2. Muscle mass increase
  3. Penile and scrotal growth
  4. Vocal cord thickening
  5. Spermatogenesis
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10
Q

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

A
  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
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11
Q

What is ARA70? Significance?

A

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

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12
Q

What happens if ARA70 is not present?

A

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

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13
Q

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

A

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?)

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14
Q

What is androgen therapy?

A

Receptor agonists

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15
Q

What is anti-androgen therapy?

A 
Receptor antagonists
Synthesis inhibitors (inhibitors of 5alpha reductase)
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16
Q

Do we have mixed agonist/antagonist for androgens?

A

NO

17
Q

What are synthetic androgens used for?

A
  1. Androgen replacement therapy
    • hypogonadism
    • aging males
  2. Protein anabolic effects
    • post surgical states, chemotherapy recuperation
  3. Anemia
  4. Anabolic steroids in athletics
18
Q

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

A

Differences in which way –OH pointing

-Significance is that the different positions have different functions

19
Q

What is the function of 17alpha testosterone?

A

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

20
Q

What is the function of 17beta testosterone?

A

Comparable potency to testosterone

21
Q

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

A

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

22
Q

What is the drug used to target BPH?

A

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

23
Q

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

A
  1. Anabolic effects

2. EPO effects

24
Q

What are the drugs used to treat prostate cancer?

A
  1. Finasteride

2. Flutamide

25
Q

What are the disadvantages of anabolic steroids in men?

A
  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
26
Q

What are disadvantages of anabolic steroids in women?

A
  1. Inhibition of LH/FSH
  2. Anovular cycles/infertility
  3. loss of libido
  4. virilization
  5. liver and CV toxicity
27
Q

What are the types of synthesis inhibition drugs?

A
  1. 5a –reductase inhibition

e. g. Finasteride

28
Q

What is Finasteride?

A

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

29
Q

What drug targets Type II 5a reductase?

A

Finasteride

30
Q

What are the types of receptor antagonists?

A
  1. Flutamide
  2. Cyproterone
  3. Spironolactone
31
Q

How do you treat prostatic cancer?

A
  1. LH-RH agonists
    • Goserelin, Leuprolide
  2. Receptor antagonists
    • Flutamide, nilutamide
32
Q

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

A

Inhibits ARA70

33
Q

How are the effects of T and DHT determined?

A

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

34
Q

How do you treat hypogonadism/pituitarism?

A

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

35
Q

What are LHRH agonists?

A

Luteinizing hormone-releasing hormone

Reproduction Week 2 (14 decks)

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