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Anabolic-Androgenic Steroids (AAS)

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Anabolic-Androgenic Steroids (AAS) www.epi.burnet.edu.au/ recentprojects/steroids www.bigfrog.net/ archives/2003/05/ Mickey Kivitz CHEM 5398 3/30/06 – PowerPoint PPT presentation

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Title: Anabolic-Androgenic Steroids (AAS)


1
Anabolic-Androgenic Steroids (AAS)
www.epi.burnet.edu.au/ recentprojects/steroids
www.bigfrog.net/ archives/2003/05/
  • Mickey Kivitz
  • CHEM 5398
  • 3/30/06

2
What are Steroids?
  • Endocrine hormones chemical signals released
    into the bloodstream which act upon target
    receptors far away from their site of release.
  • Produced by body and made synthetically in the
    lab.
  • Classes of Steroids
  • Naturally occurring
  • Androgens
  • Corticoids
  • Estrogens
  • Progestogens
  • Synthetic
  • Anabolic-Androgenic
  • Medicinal versus performance enhancing

3
History of AAS
  • Testosterone discovered in 1935 by independent
    European researchers (1).
  • All AAS are synthetic derivatives of
    testosterone.
  • Anabolic steroids initially used in medicine to
    treat hypogonadism a condition in which testes
    produce abnormally low testosterone levels (2).
  • Bodybuilders and weightlifters first used
    anabolic steroids in 1930s to increase skeletal
    muscle mass (2).
  • Current uses
  • Serving medicinal purposes (treating delayed
    puberty, impotence and muscle deterioration
    brought upon by HIV infection) (2).
  • Athletic manipulation and taboo.

4
Natural Steroid Derivatives Cholesterol and
Testosterone
17 carbon atoms in a 4-ringed structure.
cyclopentanoperhydrophenanthrene
www.people.vcu.edu/ urdesai/intro.htm (3)
Testosterone (4)
Cholesterol (4)
5
Steroids as Hormones
  • The body uses hormones to maintain a stable
    internal environment as well as perform
    long-lasting communication.
  • Because AAS are cholesterol derivates, they are
    nonpolar and readily cross the plasma membrane.
  • However, they are insoluble in aqueous
    environments and require plasma protein
    co-transporters when circulating through blood
    (5).

6
Common Steroid Hormones
Aldosterone
Cortisol (4)
www.icgeb.org/p450srv/ ligand/aldosterone.html
(6)
(4)
Progesterone (4)
7
Physiological Synthesis of Androgens
  • Manufacture by testis (initiated by luteinizing
    hormone) and adrenal cortex, and to a lesser
    degree by the ovaries.
  • Androgen Receptor (AR) exists in reproductive as
    well as non-reproductive tissue (i.e. skeletal
    muscle, etc).
  • Specificity of action varies based on
    testosterone derivative structure.
  • Action at tissue or organ also depends on AR
    quantity. For example, prostate has 25X more AR
    than skeletal muscle (7).

8
AAS as Drugs
  • Medicinal Therapeutic effects of testosterone
    replacement
  • Restore muscle mass in degenerative states, such
    as hypogonadism, HIV-related muscle wasting
    conditions, sarcopenia (age-related muscle loss)
    (8).
  • Performance Enhancing Effects
  • Commonly self-administered, therefore little
    empirical evidence.
  • Increased strength and body weight due to
    heightened skeletal muscle mass (8)
  • Numerous side effects.

9
Common AAS Substances
Androstenedione (Andro) (4)
Deca-Durabolin (Nandrolone ester) (4)
Methandrostenolone (Dianabol) (4)
Oxymetholone (anadrol) (4)
10
Androgen Receptor Binding
  • AR exists in multiple tissue types (4).
  • Binds ligand in cytoplasm and translocates into
    nucleus (8)
  • Functional domains DNA binding domain, hinge
    domain and hormone binding domain.
  • Androgens are AR agonists and facilitate
    appropriate gene activation.

www.molfunction.com/ tutorial.htm (9)
11
AR-Agonist Binding Interactions
  • AR activity is contingent upon ligand binding, AR
    homodimerization and subsequent nuclear
    localization to activate transcription of target
    genes (10).
  • Local effects such as increased skeletal muscle
    mass and strength occur due to heightened ability
    to fixate nitrogen, facilitating protein
    synthesis (1), as well as erythropoiesis (11).

12
AR Competition Anti-androgens
  • Androgen antagonists
  • Method of action
  • Suppresses testosterone activity by competing for
    AR binding site.
  • Therapeutic uses include prostate cancer, benign
    prostatic hyperplasia, hypersexuality and others
    counteracts androgen-caused diseases (4).

Cyproterone (4)
13
Methods of AAS Use
  • Administration of AAS may occur through multiple
    routes and often in combination (stacking) (12).
  • Intramuscular injection, orally, and in gels or
    creams that are rubbed on the skin.
  • Self-administration is common and often occurs in
    a regimented pattern. (8)
  • User cycles may last between 4 and 12 weeks, with
    off-cycles occuring between using periods.
  • Athletes using AAS (doping) cycle during training
    and compete in the off-cycle in hopes of
    circumventing drug tests.
  • AAS may be used in combination with accessory
    drugs and dietary supplements to maximize results
    (8)

14
Why Abuse AAS?
  • Most common reason improve athletic performance.
  • Also, to gain rapid and substantial muscle size
    and/or reduce body fat in an effort to attain a
    desired physical appearance (12)
  • Reinforcement issues in addition to initial
    physical gains, androgen receptors in the brain
    stimulate feelings of euphoria and increased
    aggressiveness. Additional use is perpetuated as
    one becomes less receptive to outside opinion and
    resorts to aggressive behavior to continue the
    cycle (1).
  • AAS reduce recovery time between periods of
    strenuous metabolic activity (8), but evidence
    remains minimal (13).
  • No proven effect on endurance or stamina (13).

15
Side Effects of AAS
  • Mild increased sexual drive, acne, increased
    body hair and baldness, aggressive behavior (13).
  • Prolonged use interferes with ability to
    naturally produce testosterone in the face of
    withdrawl (13).
  • Common problems of AAS due to chronic abuse also
    include hypertension, atherosclerosis, blood
    clotting, jaundice, hepatic carcinoma, tendon
    damage, and reduced fertility in males (11).
  • Severe life threatening side effects include
    heart attacks and liver cancer (12).

16
Prevalence of Drug Usage
  • International Olympic Committee placed anabolic
    steroids on their list of banned substances in
    1975 (11).
  • AAS put on list of Schedule III Controlled
    Substances in 1990, making it available only by
    prescription. However, recent studies indicate
    that use may be on the rise (8).
  • 1999 survey amongst middle school and high school
    students showed an increase in lifetime use by
    10th graders, alongside a decrease in risk of
    perceived harm among high school seniors (2).

17
Conclusion and Future
  • Enhancing/ understanding medical treatments
  • Fracture healing, soft tissue healing,
    postoperative rehabilitation. (8)
  • Efforts must be made to eradicate athletic use
    through education.
  • Long-term effects are currently under
    investigation, and adverse effects of AAS on
    cardiovascular, hepatic, endocrine/reproductive,
    behavioral, dermatologic systems are being
    studied (8).

18
References
  • Shahidi, Nasrollah. A Review of the Chemistry,
    Biological Action, and Clinical Applications of
    Anabolic-Androgenic Steroids. Clinical
    Therapeutics. 2001 23 1355-1390.
  • Research Report Series Anabolic Steroid Abuse
    What are anabolic steroids? National Institute
    on Drug Abuse website.
  • www.people.vcu.edu/ urdesai/intro.htm
  • http//en.wikipedia.org/wiki/Main_Page
  • Norris, David O. Vertebrate Endocrinology.
    Philadelphia Lea and Febiger, 1980 284-299.
  • www.icgeb.org/p450srv/ ligand/aldosterone.html
  • http//muscle.ucsd.edu/musintro/steroids.shtml
  • Evans, Nick A. Current Concepts in
    Anabolic-Androgenic Steroids. The American
    Journal of Sports Medicine. 2004 32 (2)
    534-542.
  • www.molfunction.com/ tutorial.htm
  • Chen, Yen, Zajac, Jeffrey D, Maclean, Helen E.
    Androgen regulation of satellite cell function.
    Journal of Endocrinology. 2005 186 21-31.
  • Mottram, DR, George, AJ. Anabolic Steroids.
    Bailleres Best Pract Res Clin Endocrinol Metab.
    2000 Mar 14 (1) 55-69.
  • Research Report Series Anabolic Steroid Abuse
    Why do people abuse anabolic steroids? National
    Institute on Drug Abuse website.
  • Hartgens, Fred, Kuipers, Harm. Effects of
    Androgenic-Anabolic Steroids in Athletes. Sports
    Medicine. 2004 34 (8) 513-554.
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