Androgenic Steroids

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Androgenic Steroids
Overall Organization of the Topic

• Overall mechanism of steroid hormone action
• Structure of male sex hormones
• - Testosterone, androstendione, and
  5a-dihydrotestosterone
• Nomenclature of androgenic steroids
• Physiological activities
• - Androgenic and anabolic activities
• Biosynthesis and metabolism of testosterone
• Structure activity relationships
• - Generalizations
• Androgen antagonists
• - Finasteride, danazol, bicalutamide and
  flutamide

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Steroid Hormones
Overall Mechanism of Steroid Hormone Action
(extracellular)
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Androgenic Steroids
Structure and Nomenclature
Androstendione (Andro)
Testosterone
(17b-hydroxy-androst-4-en-3-one) 3D-structure
(androst-4-en-3,17-dione)
5a-Dihydro-testosterone
(17b-hydroxy-5b-androstan-3-one) 3D-structure
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Androgenic Steroids Physiological Activities
Primarily two activities Androgenic and Anabolic

• Androgenic Activity
• Growth and development of male sex organs
• Important for male sex drive and performance
• Development of secondary sexual characteristics
• Important role in spermatogenesis

• Anabolic Activity
• Development of muscle mass
• Reverse catabolic or tissue-depleting processes

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Androgenic Steroids - Physiological Activities
Andro is available over the counter!!
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Biosynthesis and Metabolism of Testosterone
Testosterone
Cholesterol
Pregnenolone
Androstendione
5a-DHT
Other metabolites
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Structure Activity Relationships in Androgens
Anabolic Androgenic
Testosterone 1
1 (injectable)
Testosterone 1
1 esters (injectable)
R COCH2CH3 propionate
CO(CH2)5CH3 enanthate COCH2CH2(C5H9)
cypionate
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Structure Activity Relationships in Androgens
Anabolic Androgenic
17a-methyl Testosterone 1
1 (oral)
Fluoxymesterone 1
1 (oral)
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Structure Activity Relationships in Androgens
Anabolic Androgenic
Nandrolone 2.5
1 (injectable)
Oxymetholone 2.5
1 (oral)
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Structure Activity Relationships in Androgens
Anabolic Androgenic
Stanozolol 3
1 (oral)
Dromostanolone 4
1 (oral)
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Structure Activity Relationships in Androgens
Generalizations

• Steroid skeleton is necessary
• An electronegative (may not be oxygen) at 3
  position is required
• A/B ring fusion should be either trans or
  presence of a double bond at 4 position
• Alkyl group (CH3) at 17a-position is necessary
  for anabolic activity
• Alkyl group at 17a- confers oral activity

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Androgens Antagonists
Danazol (endometriosis)
Finesteride (baldness)
Bicalutamide (prostate cancer)
Flutamide (prostate cancer)