akn
Musclechemistry Member
A very small amount of testosterone actually exists in a
free state, where interaction with cellular receptors is
possible. The majority will be bound to the proteins SHBG
(sex hormone binding globulin, also referred to as sex
steroid binding globulin and testosterone-estradiol
binding globulin) and albumin, which temporarily prevent
the hormone from exerting activity. Steroid hormones
actually bind much more avidly to SHBG than albumin
(with approximately 1,000 times greater affinity), however
albumin is present in a level 1,000 times greater than
SHBG. Therefore, the activity of both binding proteins in
the body is relatively equal. The distribution of
testosterone in men is typically 45% of testosterone
bound to SHBG, and about 530/0 bound to albumin. The
remaining 2% of the average blood concentration exists
in a free, unbound state. In women, the percentage of free
testosterone is lower, measured to be approximately 1%. A
binding protein called ABP (androgen binding protein)
also helps to mediate androgen activity in the
reproductive system, although since it is found exclusively
in these tissues, it is not relevant to muscle growth.
The level of free testosterone available in the blood is
likewise an important factor mediating its activity, as only
a small percentage is really active at any given time. It
must also be noted that as we alter testosterone to form
new anabolic/androgenic steroids, we also typically alter
the affinity in which the steroid will bind to plasma
proteins. This is an important consideration, as the higher
percentage we have of free hormone, the more active the
compound should be on a milligram for milligram basis.
And the variance can be substantial between different
compounds. For example, Proviron® (l-methyl
dihydrotestosterone) binds with SHBG many times more
avidly than testosterone,1g while mibolerone (7,17
dimethyl-nandrolone) and bolasterone (7,17 dimethyltestosterone)
show virtually no affinity for this protein at
all (clearly the reason these steroids are such potent
androgens).
The level of SHBG present in the body is also variable, and
can be altered by a number of factors. The most
prominent seems to be the concentration of estrogen and
thyroid hormones present in the blood. We generally see a
reduction in the amount of this plasma binding protein as
estrogen and thyroid content decreases, and a rise in
SHBG as they increase. A heightened androgen level due
to the administration of anabolic/androgenic steroids has
also been shown to lower levels of this protein
considerably. This is clearly supported by a 1989 German
study, which noted a strong tendency for SHBG reduction
with the oral anabolic steroid stanozolol (Winstrol®).2o
After only 3 days of administering a daily dose of .2mg/kg
body-weight (about 18mg for a 200lb man), SHBG was
lowered nearly 50% in normal subjects. Similar results
have been obtained with the use of injectable
testosterone enanthate; however, milligram for milligram,
the effect of stanozolol was much greater in comparison.
The form of administration may have been important in
reaching this level of response. Although the injectable
was not tried in the German study, we can refer to others
comparing the effect of oral vs. transdermal estrogen.21
These show a much greater response in SHBG levels when
the drug is given orally. This is perhaps explained by the
fact that SHBG is produced in the liver. Therefore, we
cannot assume that injectable Winstrol® (or injectable
steroids in general) will display the same level of potency
in this regard.
Lowering the level of plasma binding proteins is also not
the only mechanism that allows for an increased level of
free testosterone. Steroids that display a high affinity for
these proteins may also increase the level of free
testosterone by competing with it for binding. Obviously
if testosterone finds it more difficult to locate available
plasma proteins in the presence of the additional
compound, more will be left in an unbound state. A
number of steroids including dihydrotestosterone,
Proviron®, and Oral-Turinabol
(chlorodehydromethyltestosterone) display a strong
tendency for this effect. If the level of free-testosterone
can be altered by the use of different anabolic/androgenic
steroids, the possibility also exists that one steroid can
increase the potency of another through these same
mechanisms. For example, Proviron® is a poor anabolic,
but its extremely high affinity for SHBG might make it
useful by allowing the displacement of other steroids that
are more active in these tissues.
We must not let this discussion lead us into thinking that
binding proteins serve no valuable function. In fact they
play a vital role in the transport and functioning of
endogenous androgens. Binding proteins act to protect
the steroid against rapid metabolism, ensure a more
stable blood hormone concentration, and facilitate an
even distribution of hormone to various body organs. The
recent discovery of a specific receptor for Sex HormoneBinding
Globulin (SHBG-R) located on the membrane
surface of steroid responsive body cells also suggests a
much more complicated role for this protein than solely hormone transport. However, it remains clear that
manipulating the tendency of a hormone to exist in an
unbound state is an effective way to alter drug potency.
free state, where interaction with cellular receptors is
possible. The majority will be bound to the proteins SHBG
(sex hormone binding globulin, also referred to as sex
steroid binding globulin and testosterone-estradiol
binding globulin) and albumin, which temporarily prevent
the hormone from exerting activity. Steroid hormones
actually bind much more avidly to SHBG than albumin
(with approximately 1,000 times greater affinity), however
albumin is present in a level 1,000 times greater than
SHBG. Therefore, the activity of both binding proteins in
the body is relatively equal. The distribution of
testosterone in men is typically 45% of testosterone
bound to SHBG, and about 530/0 bound to albumin. The
remaining 2% of the average blood concentration exists
in a free, unbound state. In women, the percentage of free
testosterone is lower, measured to be approximately 1%. A
binding protein called ABP (androgen binding protein)
also helps to mediate androgen activity in the
reproductive system, although since it is found exclusively
in these tissues, it is not relevant to muscle growth.
The level of free testosterone available in the blood is
likewise an important factor mediating its activity, as only
a small percentage is really active at any given time. It
must also be noted that as we alter testosterone to form
new anabolic/androgenic steroids, we also typically alter
the affinity in which the steroid will bind to plasma
proteins. This is an important consideration, as the higher
percentage we have of free hormone, the more active the
compound should be on a milligram for milligram basis.
And the variance can be substantial between different
compounds. For example, Proviron® (l-methyl
dihydrotestosterone) binds with SHBG many times more
avidly than testosterone,1g while mibolerone (7,17
dimethyl-nandrolone) and bolasterone (7,17 dimethyltestosterone)
show virtually no affinity for this protein at
all (clearly the reason these steroids are such potent
androgens).
The level of SHBG present in the body is also variable, and
can be altered by a number of factors. The most
prominent seems to be the concentration of estrogen and
thyroid hormones present in the blood. We generally see a
reduction in the amount of this plasma binding protein as
estrogen and thyroid content decreases, and a rise in
SHBG as they increase. A heightened androgen level due
to the administration of anabolic/androgenic steroids has
also been shown to lower levels of this protein
considerably. This is clearly supported by a 1989 German
study, which noted a strong tendency for SHBG reduction
with the oral anabolic steroid stanozolol (Winstrol®).2o
After only 3 days of administering a daily dose of .2mg/kg
body-weight (about 18mg for a 200lb man), SHBG was
lowered nearly 50% in normal subjects. Similar results
have been obtained with the use of injectable
testosterone enanthate; however, milligram for milligram,
the effect of stanozolol was much greater in comparison.
The form of administration may have been important in
reaching this level of response. Although the injectable
was not tried in the German study, we can refer to others
comparing the effect of oral vs. transdermal estrogen.21
These show a much greater response in SHBG levels when
the drug is given orally. This is perhaps explained by the
fact that SHBG is produced in the liver. Therefore, we
cannot assume that injectable Winstrol® (or injectable
steroids in general) will display the same level of potency
in this regard.
Lowering the level of plasma binding proteins is also not
the only mechanism that allows for an increased level of
free testosterone. Steroids that display a high affinity for
these proteins may also increase the level of free
testosterone by competing with it for binding. Obviously
if testosterone finds it more difficult to locate available
plasma proteins in the presence of the additional
compound, more will be left in an unbound state. A
number of steroids including dihydrotestosterone,
Proviron®, and Oral-Turinabol
(chlorodehydromethyltestosterone) display a strong
tendency for this effect. If the level of free-testosterone
can be altered by the use of different anabolic/androgenic
steroids, the possibility also exists that one steroid can
increase the potency of another through these same
mechanisms. For example, Proviron® is a poor anabolic,
but its extremely high affinity for SHBG might make it
useful by allowing the displacement of other steroids that
are more active in these tissues.
We must not let this discussion lead us into thinking that
binding proteins serve no valuable function. In fact they
play a vital role in the transport and functioning of
endogenous androgens. Binding proteins act to protect
the steroid against rapid metabolism, ensure a more
stable blood hormone concentration, and facilitate an
even distribution of hormone to various body organs. The
recent discovery of a specific receptor for Sex HormoneBinding
Globulin (SHBG-R) located on the membrane
surface of steroid responsive body cells also suggests a
much more complicated role for this protein than solely hormone transport. However, it remains clear that
manipulating the tendency of a hormone to exist in an
unbound state is an effective way to alter drug potency.
