AnabolicAndrogenic 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

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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

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Definitions

• Androgen Any hormone with testosterone-like
  actions
• Anabolism Cellular synthesis of organic
  molecules (including proteins).

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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.

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Hypogonadism

• Hypogonadism in adult males may alter certain
  masculine physical characteristics and impair
  normal reproductive function. Signs and symptoms
  may include?Erectile dysfunction?Infertility?Decr
  ease in beard and body hair growth?Increase in
  body fat?Decrease in size or firmness of
  testicles?Decrease in muscle mass?Development of
  breast tissue?Loss of bone mass (osteoporosis )

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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)
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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).

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Common Steroid Hormones
Aldosterone
Cortisol (4)
www.icgeb.org/p450srv/ ligand/aldosterone.html
(6)
(4)
Progesterone (4)
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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).

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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.

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Common Anabolic Adrogenic Steroids
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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)
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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
  (production of red blood cells) (11).

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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)
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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)

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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).

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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).

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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).

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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).

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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.