Title: Anabolic-Androgenic Steroids (AAS)
1Anabolic-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
3History 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.
4Natural 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)
5Steroids 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).
6Common Steroid Hormones
Aldosterone
Cortisol (4)
www.icgeb.org/p450srv/ ligand/aldosterone.html
(6)
(4)
Progesterone (4)
7Physiological 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).
8AAS 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.
9Common AAS Substances
Androstenedione (Andro) (4)
Deca-Durabolin (Nandrolone ester) (4)
Methandrostenolone (Dianabol) (4)
Oxymetholone (anadrol) (4)
10Androgen 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)
11AR-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).
12AR 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)
13Methods 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)
14Why 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).
15Side 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).
16Prevalence 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).
17Conclusion 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).
18References
- 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.