STEROIDS 1

Steroids
Steroids are a class of organic compounds with a
chemical structure that contains the core of gonane or a
skeleton derived therefrom.
Examples of steroids include cholesterol, the sex
hormones estradiol and testosterone, and the anti-
inflammatory drug dexamethasone. Hundreds of distinct
steroids are found in plants, animals, and fungi. All
steroids are made in cells either from the sterols
lanosterol (animals and fungi) or from cycloartenol
(plants). Both lanosterol and cycloartenol are derived
from the cyclization of the triterpene squalene.

STEROID METABOLISM

Metabolism
Steroids include estrogen, cortisol, progesterone, and testosterone.
Estrogen and progesterone are made primarily in the ovary and in the
placenta during pregnancy, and testosterone in the testes. Testosterone is
also converted into estrogen to regulate the supply of each, in the bodies
of both females and males. Certain neurons and glia in the central
nervous system (CNS) express the enzymes that are required for the
local synthesis of pregnane neurosteroids, either de novo or from
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peripherally-derived sources. The rate-limiting step of steroid synthesis

is the conversion of cholesterol to pregnenolone, which occurs inside the
mitochondrion.

Steroid metabolism is the complete set of chemical reactions in

organisms that produce, modify, and consume steroids. These metabolic
pathways include:
• steroid synthesis – the manufacture of steroids from
simpler precursors
• steroidogenesis – the interconversion of different
types of steroids
• steroid degradation.

A. Steroid biosynthesis
Steroid biosynthesis is an anabolic metabolic pathway that produces
steroids from simple precursors. This pathway is carried out in different
ways in animals than in many other organisms, making the pathway a
common target for antibiotics and other anti-infective drugs. In addition,
steroid metabolism in humans is the target of cholesterol-lowering drugs
such as statins.
It starts in the mevalonate pathway in humans, with Acetyl-CoA as
building blocks, which form DMAPP and IPP. In following steps,
DMAPP and IPP form lanosterol, the first steroid. Further modification
belongs to the succeeding steroidogenesis.
Mevalonate pathway
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The mevalonate pathway or HMG-CoA reductase pathway starts

with and ends with dimethylallyl pyrophosphate (DMAPP) and
isopentenyl pyrophosphate (IPP).
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DMAPP to lanosterol
Isopentenyl pyrophosphate and dimethylallyl pyrophosphate donate
isoprene units, which are assembled and modified to form terpenes and
isoprenoids[8], which are a large class of lipids that include the
carotenoids, and form the largest class of plant natural products.
Here, the isoprene units are joined together to make squalene and then
folded up and formed into a set of rings to make lanosterol. Lanosterol
can then be converted into other steroids such as cholesterol and
ergosterol
B. Steroidogenesis
Steroidogenesis is the biological process by which steroids are
generated from cholesterol and transformed into other steroids. The
pathways of steroidogenesis differ between different species.
Products of steroidogenesis include:
• androgens

○ testosterone

• estrogens and progesterone

• corticoids

○ cortisol

○ aldosterone

C. Elimination
Steroids are oxidized mainly by cytochrome P450 oxidase enzymes,
such as CYP3A4. These reactions introduce oxygen into the steroid ring
and allows the structure to be broken up by other enzymes, to form bile
acids as final products. These bile acids can then be eliminated through
secretion from the liver in the bile. The expression of this oxidase gene
can be upregulated by the steroid sensor PXR when there is a high blood
concentration of steroids.
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Anabolic steroids
Anabolic steroids are drugs that resemble androgenic hormones
(sometimes called male hormones) such as testosterone (Figure 1).
Athletes consume them in the hope of gaining weight, strength, power,
speed, endurance, and aggressiveness. They are widely used by athletes
involved in such sports as track and field (mostly the throwing events),
weight lifting, and American football. However, in spite of their
tremendous popularity, their effectiveness is controversial. The research
literature is divided on whether anabolic steroids enhance physical
performance. Yet, almost all athletes who consume these substances
acclaim their beneficial effects. Many athletes feel that they would not
have been as successful without them.
There are several possible reasons for the large differences between
experimental findings and empirical observations. An incredible
mystique has arisen around these substances, providing fertile ground
for the placebo effect. The use of anabolic steroids in the "real world" is
considerably different from that in rigidly controlled, double-blind
experiments (in a double blind study, neither the subject nor
experimenter knows who is taking the drug). Most studies have not used
the same drug dosage used by athletes. Institutional safeguards prohibit
administration of high dosages of possibly dangerous substances to
human subjects. Subjects in research experiments seldom resemble
accomplished weight-trained athletes. Under these conditions, we must
assess the results of sound research studies, as well as clinical and
empirical field observations, in order to obtain a realistic profile of the
use, effects on performance, and side effects of these substances.
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How Anabolic Steroids Work ?

Male hormones, principally testosterone, are partially responsible for the
tremendous developmental changes that occur during puberty and
adolescence. Male hormones have androgenic and anabolic effects.
Androgenic effects are changes in primary and secondary sexual
characteristics. These include enlargement of the penis and testes, voice
changes, hair growth on the face, axilla, and genital areas, and increased
aggressiveness. The anabolic effects of androgens include accelerated
growth of muscle, bone, and red blood cells, and enhanced neural
conduction.
Anabolic steroids have been manufactured to enhance the anabolic
properties (tissue building) of the androgens and minimize the
androgenic (sex-linked) properties. However, no steroid has eliminated
the androgenic effects because the so-called androgenic effects are really
anabolic effects in sex-linked tissues. The effects of male hormones on
accessory sex glands, genital hair growth, and oiliness of the skin are
anabolic processes in those tissues. The steroids with the most potent
anabolic effect are also those with the greatest androgenic effect

Steroid Receptors
Steroid hormones work by stimulation of receptor molecules in muscle
cells, which activate specific genes to produce proteins (see Figure 1).
They also affect the activation rate of enzyme systems involved in
protein metabolism, thus enhancing protein synthesis and inhibiting
protein degradation (called an anti-catabolic effect).
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Figure 1: How a Steroid Hormone Works

Heavy resistance training seems to be necessary for anabolic steroids to

exert any beneficial effect on physical performance. Most research
studies that have demonstrated improved performance with anabolic
steroids used experienced weight lifters who were capable of training
with heavier weights and producing relatively greater muscle tension
during exercise than novice subjects. The effectiveness of anabolic
steroids is dependent upon unbound receptor sites in muscle. Intense
strength training may increase the number of unbound receptor sites.
This would increase the effectiveness of anabolic steroids.

Anti-Catabolic Effects Of Anabolic

Steroids

Many athletes have said that anabolic steroids help them train harder and
recover faster. They also said that they had difficulty making progress
(or even holding onto the gains) when they were off the drugs. Anabolic
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steroids may have an anti-catabolic effect. This means that the drugs
may prevent muscle catabolism that often accompanies intense exercise
training. Presently, this hypothesis has not been fully proven.
Anabolic steroids may block the effects of hormones such as cortisol
involved in tissue breakdown during and after exercise. Anabolic
steroids may prevent tissue from breaking down following of an intense
work-out. This would speed recovery. Cortisol and related hormones,
secreted by the adrenal cortex, also has receptor sites within skeletal
muscle cells. Cortisol causes protein breakdown and is secreted during
exercise to enhance the use of proteins for fuel and to suppress
inflammation that accompanies tissue injury.
Anabolic steroids may block the binding of cortisol to its receptor sites,
which would prevent muscle breakdown and enhances recovery. While
this is beneficial while the athlete is taking the drug, the effect backfires
when he stops taking it. Hormonal adaptations occur in response to the
abnormal amount of male hormone present in the athlete's body. Cortisol
receptor sites and cortisol secretion from the adrenal cortex increase.
Anabolic steroid use decreases testosterone secretion. People who stop
taking steroids are also hampered with less male hormone than usual
during the "off" periods. The catabolic effects of cortisol are enhanced
when the athlete stops taking the drugs and strength and muscle size are
lost at a rapid rate.
The rebound effect of cortisol and its receptors presents people who use
anabolic steroids with several serious problems:
(1) psychological addiction is more probable because they become
dependent on the drugs. This is because they tend to lose strength and
size rapidly when off steroids. To stave off deconditioning, athletes may
want to take the drugs for long periods of time to prevent falling behind.
(2) Long-term administration increases the chance of serious side-
effects.
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(3) Cortisol suppresses the immune system. This makes steroid users
more prone to diseases, such as cold and flu, during the period
immediately following steroid administration.
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Psychological Effects

Some researchers have speculated that the real effect of anabolic steroids
is the creation of a "psychosomatic state" characterized by sensations of
well being, euphoria, increased aggressiveness and tolerance to stress,
allowing the athlete to train harder. Such a psychosomatic state would be
more beneficial to experienced weight lifters who have developed the
motor skills to exert maximal force during strength training. Diets high
in protein and calories may also be important in maximizing the
effectiveness of anabolic stero
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Anabolic Steroids and Performance

The effects of anabolic steroids on physical performance are unclear.

Well controlled, double blind studies have rendered conflicting results.
In studies showing beneficial effects, body weight increased by an
average of about four pounds, lean body weight by about six pounds (fat
loss accounts for the discrepancy between gains in lean mass and body
weight), bench press increased by about 15 pounds, and squats by about
30 pounds (these values represent the average gains for all studies
showing a beneficial effect). Almost all studies have failed to
demonstrate a beneficial effect on maximal oxygen consumption or
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endurance capacity. Anabolic steroid studies have typically lasted six to

eight weeks and have usually used relatively untrained subjects.
Most changes in strength during the early part of training are neural:
increased strength is mainly due to an improved ability to recruit motor
units. Anabolic steroids affect processes associated with protein
synthesis in muscle. Studies lasting six weeks (typical study length)
would largely reflect neural changes and could easily miss the cellular
effects of the drugs.
The gains made by athletes in uncontrolled observations have been
much more impressive. Weight gains of thirty or forty pounds, coupled
with thirty percent increases in strength, are not unusual. Such case
studies lack credibility because of the absence of scientific controls.
However, it would be foolish to completely disregard such observations
because the "subjects" have been highly trained and motivated
athletes.Please see the articles on pharmacology of sport and sports
medicine in the countries of the former Soviet Union for more
information on anabolic steroids.