<header class="entry-header" style="box-sizing: border-box; font-family: 'Source Sans Pro', sans-serif; font-size: 18px; line-height: 29px; ">[h=1]Free Unbound Testoserone versus shbg Bound[/h]</header>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 testosteroneestradiol 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 53% 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® (1-methyl dihydrotestosterone) binds with SHBG many times more avidly than testosterone,19 while mibolerone (7,17 dimethyl-nandrolone) and bolasterone (7,17 dimethyl- testosterone) 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®). After only 3 days of administering a daily dose of .2mg/kg bodyweight (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. 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 Hormone Binding 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.
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® (1-methyl dihydrotestosterone) binds with SHBG many times more avidly than testosterone,19 while mibolerone (7,17 dimethyl-nandrolone) and bolasterone (7,17 dimethyl- testosterone) 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®). After only 3 days of administering a daily dose of .2mg/kg bodyweight (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. 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 Hormone Binding 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.
