steroids2b javier, dan, alex, gwenael

ToTo or not toor not to“Juice”“Juice” “Juice”“Juice”

Javier AmigonDaniel HoAlex LukatskiyGwenael Gatto

Javier AmigonDaniel HoAlex LukatskiyGwenael Gatto

By:By:

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Supplemental Testosterone in SportsSupplemental Testosterone in Sports

Testosterone is a naturally occurring steroid.

Testosterone is a naturally occurring steroid.

BackgroundBackground

2

3

4

5

10

1

6

7

8

9 14

13

12

11

15

16

17

O

19H

18 OH22

HH

H 25

AB

CD

TestosteroneTestosterone

Androgenic effects

-Male secondary sex characteristics

Androgenic effects

-Male secondary sex characteristics

Anabolic Effects Anabolic Effects

Medical Use Medical Use

Schematic Representation of Intermolecular Interactions between Testosterone and Amino Acids in the Ligand Binding Domain of the Androgen ReceptorSchematic Representation of Intermolecular Interactions between Testosterone and Amino Acids in the Ligand Binding Domain of the Androgen Receptor

Hydrogen Bonding

Testosterone in the Androgen ReceptorTestosterone in the Androgen Receptor

Schematic Representation of Intermolecular Interactions between Testosterone and Amino Acids in the Ligand Binding Domain of the Androgen ReceptorSchematic Representation of Intermolecular Interactions between Testosterone and Amino Acids in the Ligand Binding Domain of the Androgen Receptor

Van der WaalsForces

Testosterone in the Androgen ReceptorTestosterone in the Androgen Receptor

T

Cell MembraneCell Membrane NucleusNucleusCytoplasmCytoplasm

T A Muscle Growth Muscle Growth

DNADNA

Biological Mechanism of TestosteroneBiological Mechanism of Testosterone

Testosterone banned (1991, Controlled Substances Act) Testosterone banned (1991, Controlled Substances Act)

Testosterone is Banned in SportsTestosterone is Banned in Sports

Emergence of testosterone precursors.

Ex. Androstenedione (“Andro”) -1998

Emergence of testosterone precursors.

Ex. Androstenedione (“Andro”) -1998

Dietary supplements Dietary supplements

Testosterone in SportsTestosterone in Sports

Athlete’s desire to improve athletic performance. Athlete’s desire to improve athletic performance.

Floyd Landis- Tour de FranceFloyd Landis- Tour de France Mark McGwire –Major League BaseballMark McGwire –Major League Baseball

Notable Athletes:Notable Athletes:

Supplemental testosterone via injections, pills or topical creams. Supplemental testosterone via injections, pills or topical creams.

Synthesis of AndrostenedioneSynthesis of Androstenedione

CorticosteroneCorticosterone

1. Na+ -OCH3

o

o

2.

O

O

OH

O

H

OH

H H

O

OCH 3

Keto-Enol TautomerizationKeto-Enol Tautomerization

O

H

O

H

O

O

H

OH

H

O

Synthesis of Androstenedione (cont.)Synthesis of Androstenedione (cont.)

AndrostenedioneAndrostenedione

..

........ -

+ +

Proton NMR Spectroscopy

Proton NMR Spectroscopy

AndrostenedioneO

O

H

HHH

H H

(s, 6H)

Testosterone

Electron donating effects of oxygen.

Neighboring protons more shielded.

Electron donating effects of oxygen.

Neighboring protons more shielded.

Proton NMR Spectroscopy

Proton NMR Spectroscopy

(S,1H)

H

(t,1H)

HH

H

HH

H

(s,3H)

(s,3H)

Androstenedione

IR SpectroscopyIR Spectroscopy

O

O

OH

O

Testosterone

IR SpectroscopyIR Spectroscopy

Does Androstenedione Make You Stronger?Does Androstenedione Make You Stronger?

Increases estrone and estradiol levels in men Increases estrone and estradiol levels in men

AndrostenedioneAndrostenedione

O

O

OH

O

OH

HO

AromataseAromatase

TestosteroneTestosterone EstradiolEstradiol

O

HO

Aromatase

Aromatase

EstroneEstrone

The Result?The Result?

Man Boobs! (aka Gynecomastia)Man Boobs! (aka Gynecomastia)

ConclusionsConclusions

Desired results not achieved. Desired results not achieved.

Other methods to bypass laws. Other methods to bypass laws.

Designer Steroids

- BALCO, Olympics

Designer Steroids

- BALCO, Olympics

How to stay ahead of designer steroid manufacturers? How to stay ahead of designer steroid manufacturers?

ReferencesReferences

Floyd Landis:http://www.roadcycling.com/artman/uploads/5_landis_podium_002.jpg

Mark McGwire:http://www.misunderestimation.com/wp-content/uploads/2007/01/GotJuice.jpg

Homer Simpson:http://users.bigpond.net.au/simpsons/mirror.jpg

Health Effects of Androstenedione. FDA White Paper. U.S. Food and Drug Administration. Retrieved on 4/13/09. http://www.fda.gov/oc/whitepapers/andro.html. Health Effects of Androstenedione. FDA White Paper. U.S. Food and Drug Administration. Retrieved on 4/13/09. http://www.fda.gov/oc/whitepapers/andro.html.

FDA Warning on Androstenedione (Andro). National Center for Complementary and Alternative Medicine. Retrieved on 4/24/09. http://nccam.nih.gov/news/alerts/androstenedione/consumeradvisory.htm.FDA Warning on Androstenedione (Andro). National Center for Complementary and Alternative Medicine. Retrieved on 4/24/09. http://nccam.nih.gov/news/alerts/androstenedione/consumeradvisory.htm.

Koert , Willem and Aede de Groot. The Anabolics Book. Retrieved on 4/10/09. http://www.ergogenics.org/anabolenboek/index21en.html.Koert , Willem and Aede de Groot. The Anabolics Book. Retrieved on 4/10/09. http://www.ergogenics.org/anabolenboek/index21en.html.

Yesalis, Charles E. (1999). Medical, Legal, and Societal Implications of Androstenedione Use. JAMA. 1999;281(21):2043-2044.Yesalis, Charles E. (1999). Medical, Legal, and Societal Implications of Androstenedione Use. JAMA. 1999;281(21):2043-2044.

Leder et al. (2002). Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women. The Journal of Clinical Endocrinology & Metabolism 87(12):5449–5454.Leder et al. (2002). Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women. The Journal of Clinical Endocrinology & Metabolism 87(12):5449–5454.

Cawley et al. The detection of androstenedione abuse in sport: a mass spectrometry strategy to identify the4-hydroxyandrostenedione metabolite. Rapid Commun. Mass Spectrom. 2008; 22: 4147–4157.Cawley et al. The detection of androstenedione abuse in sport: a mass spectrometry strategy to identify the4-hydroxyandrostenedione metabolite. Rapid Commun. Mass Spectrom. 2008; 22: 4147–4157.

Le Pera et al (2003). A straightforward chemical synthesis of 17-ketosteroids by cleavage of the C-17-dihydroxyacetoneSide chain in corticosteroids. Steroids 68 (2003) 139–142.Le Pera et al (2003). A straightforward chemical synthesis of 17-ketosteroids by cleavage of the C-17-dihydroxyacetoneSide chain in corticosteroids. Steroids 68 (2003) 139–142.