Androgenic SteroidsAndrogenic Steroids

Overall Organization of the Topic

Overall mechanism of steroid hormone action Structure of male sex hormones

- Testosterone, androstendione, and 5-

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

Steroid HormonesSteroid Hormones

Overall Mechanism of Steroid Hormone Action

(extracellular)

(intracellular)

(intranuclear)

proteinsIntracellular effects

extracellular effects

transcriptiontranslation

dimerization

DNA

Androgenic SteroidsAndrogenic Steroids

CH3

OH

O

CH3

CH3

O

CH3O

CH3

OH

O

CH3

H

Androstendione(Andro)

5-Dihydro-testosterone

Testosterone

Structure and Nomenclature

(17-hydroxy-androst-4-en-3-one)3D-structure (androst-4-en-3,17-dione)

(17-hydroxy-5-androstan-3-one)3D-structure

Androgenic Steroids – Physiological ActivitiesAndrogenic Steroids – Physiological Activities

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

Primarily two activities – Androgenic and Anabolic

Anabolic Activity

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

Andro is available over the counter!!

Androgenic Steroids - Physiological Androgenic Steroids - Physiological ActivitiesActivities

Biosynthesis and Metabolism of TestosteroneBiosynthesis and Metabolism of Testosterone

CH3

CH3

OH

CH3

CH3CH3

O

OH

CH3

CH3OH

O

CH3

O

CH3O

CH3

OH

O

CH3

H

CH3

CH3

HOH

OH

Cholesterol Pregnenolone Testosterone

Androstendione5-DHTOther metabolites

Structure Activity Relationships in AndrogensStructure Activity Relationships in Androgens

CH3

OH

O

CH3Anabolic Androgenic

Testosterone 1 1(injectable)

CH3

OR

O

CH3

Testosterone 1 1esters (injectable)

R = COCH2CH3 propionate

= CO(CH2)5CH3 enanthate

= COCH2CH2(C5H9) cypionate

Structure Activity Relationships in AndrogensStructure Activity Relationships in Androgens

CH3

OH

O

CH3CH3

Anabolic Androgenic

17-methylTestosterone 1 1(oral)

CH3

OH

O

CH3OH

F

CH3

Fluoxymesterone 1 1(oral)

Structure Activity Relationships in AndrogensStructure Activity Relationships in Androgens

Anabolic Androgenic

Nandrolone 2.5 1(injectable)

H

OH

O

CH3

CH3

OH

O

CH3CH3

OH

H

Oxymetholone 2.5 1(oral)

Structure Activity Relationships in AndrogensStructure Activity Relationships in Androgens

Anabolic Androgenic

Stanozolol 3 1(oral)

Dromostanolone 4 1(oral)

CH3

OH

N

CH3CH3

NH

H

CH3

OH

O

CH3

H

CH3

CH3

Structure Activity Relationships in AndrogensStructure Activity Relationships in Androgens

CH3

OHCH3CH2CH3

H

OHCH3CH2CH3

O

CH3

OCOCH3

O

CH3

H

CH3

CH3

OCOCH3

O

CH3

Cl

O

CH3

OH

O

CH3CH3

H

Ethylestrenol (4 mg/day)

Norethandrolone10-30 mg/day

Methenolone acetate (20 mg /wk)

Chlorotestosterone acetate (20 mg / wk)

Oxandrolone (5-10 mg/day)

CH3

OH

O

CH3CH3

17-methyl testosterone(10-50 mg/day)

Androgens AntagonistsAndrogens Antagonists

NH

CF3

S

F

CN

O O O

CH3OHNH

CF3

O

CH3

NO2

CH3

O

CH3

CH3OH

CH

N

CH3

CH3

NH

O

O

NH

CH3CH3CH3

HDanazol

(endometriosis)Finesteride(baldness)

Bicalutamide(prostate cancer)

Flutamide(prostate cancer)