Anabolic-Androgenic Steroids

• Anabolic: stimulate muscle growth• Androgenic: stimulate male sex characteristics

Androstane

CH3

CH3

H

5 -Androstane

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Male Sex Hormones

Before Castration

AfterCastration

• It was deduced that a secretion of the testes was responsible for male sex characteristics

Testis Extract and Hormones from Urine

Me

Me O

HO

Androsterone

Isolated from UrineLess activity than testis extract

Testis extract: High activity

Me

Me O

O

Androstenedione

More activity but still less than testis extract

Testosterone

Me

MeOH

O

Testosterone

Separation of Androgenicand Anabolic Effects

Me

MeOH

O

Testosterone

Me

MeOH

O

Dihydrotestosterone

5 - reductase

H

MoreActivity

• Receptors for testosterone have the same affinity in the sex accessory organs as in skeletal muscle

Nandrolone

H

MeOH

O

19-Nortestosterone(Nandrolone)

H

MeOH

O

5 -Dihydro-19-nortestosterone(5 -Dihydronandrolone)

5 - reductase

H

Higher activitythan testosterone

Lower activitythan testosterone

Metabolic Deactivationof Testosterone

Me

MeOH

O

HSD

Me

MeOH

OH

HSDMe

MeO

HO

Me

MeO

O

Testosterone Androstenedione

5 - reductase

5 -Dihydrotestosterone Androsterone

reduction at C-3

17α-substituted Derivatives

Me

MeOH

Me

17 -Methyltestosterone

O

17β- Esters

Me

MeO

O

Testosterone Propionate

O

Structure Activity Relationship

Me

MeOH

Me

17 -methylandrost-2-ene-17 -ol

C-3 Oxygennot important

CN

MeOH

O

Me

19 -cyano-17 -methyltestosterone

antagonist

Me

MeOH

OMe

7 -methyltestosterone

- substituenthas no effect

Performance Enhancers

• 17α- alkyl and 17β- esters are not suitable for illegal use by athletes because of their prolonged life and ease of detection

• Prohormones are metabolized into active anabolics and occur naturally in the body

AndrostenedioneDHEA

Me

MeO

HO

Dehydroepiandrosterone

Side Effects

Side Effects of Anabolic-Androgenic Steroids

Both Sexes Men Women

Increased risk of heart attack and stroke

Testicular atrophy

Clitoral enlargement

Increased aggression impotence Beard growth

Liver tumors, jaundice, peliosis hepatitis

Enlarged prostrate

Deepened voice

baldness Breast enlargement

Breast diminution

References

1. Kochakian, C. D. “History of Anabolic-Androgenic Steroids.” Anabolic Steroid Abuse. 1990, 29-50.2. Block, John H. Beale, John M. Organic Medicinal and Pharmaceutical Chemistry. Pa: Lippincott Williams and Wilkins. 2004.3. Kochakian, C. D. “The Effects of Male Hormone on the Protein and Energy Metabolism of Castrate Dogs.” Journal of Nutrition. 1935. 437-59.4. Bowers, A. Edwards, J. “Steroids: Ring A Modified Hormone Analogs, Part 1.” Journal of Medicinal Chemistry. 6. 1962. 5. Celotti, F. Cesi, P. “Anabolic Steroids: A review of their effects on the muscles, of their possible mechanisms of action and of their use in athletics.” Journal of Steroid Biochemistry and Molecular Biology. 43(5). 1992. 469-77.6. Krieg, M. “Characterization of the androgen receptors in the muscle of the rat.” Steroids 28. 1976. 261-74.7. Counsell, R. E. Adelstein, G. W. “!9-Nor- and 19-Substituted 5a-Androst-2-ene Derivatives” Journal of Medicinal Chemistry. 1966. 685-9.8. Delbeke, Frans T. “Prohormones and Sport.” Journal of Steroid Biochemistry and Molecular Biology. 83. 2003. 245-51.