- Jun 25, 2006
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STEROIDS and CYCLES
by: DatbTrue
Lets take a look at hormones
In tissue associated with reproduction (such as prostate and seminal vesicles), Testosterone acts as a prohormone and is irreversibly converted by the enzyme 5a-reductase to a more potent androgen 5a-dihydrotestosterone (DHT). 5a-dihydrotestosterone (DHT), is considered more potent because it binds with greater affinity to the androgen receptor (AR) and therefore is strongly androgenic.
In other tissues, such as adipose tissue and parts of the brain, Testosterone is converted by the aromatase enzyme to the hormone estrogen and estradiol which binds to the estrogen receptor.
In bone Testosterone exerts its effect by acting both directly and by aromatizing to estradiol.
In skeletal muscle there is no 5a-reductase activity. Intracellular DHT is very low in skeletal muscle, and its presence is further diminished because of the high activity of the enzyme 3a-hydroxysteroid-dehydrogenase in this tissue (and cardiac tissue as well). This enzyme converts DHT irreversibly to 3a-androstanediol. So in skeletal muscle tissue testosterone itself is primarily binding to the androgen receptor. However aromatase expression and activity is significant and the conversion of testosterone to estrogen is ongoing. It has not yet been determined to what extent if any estrogen plays in mediating some of muscle building effects of androgens but it appears to play a role. In skelelatol muscle it is present and active.
Testosterone and DHT can also be converted to weaker androgens, if the target tissue posses the necessary enzyme activity (i.e. 3a-hydroxysteroid dehydrogenase, 17b-hydroxysteroid dehydrogenase).
Modulators of androgens
The effects of androgens at the molecular level can vary. The events that are engendered by androgens when they bind to an Androgen Receptor can be increased or decreased depending on the distribution of what is known as androgen receptor coregulators. This distribution can vary throughout various tissues and change throughout time. These coregulators are simply proteins that affect the transcriptional activity of the androgen receptor. For example one category of coregulator stabilizes the ligand-bound receptor (i.e. the androgen molecule bound to its receptor) while others facilitate the translocation (or movement) of the ligand-bound receptor (i.e. the androgen molecule bound to its receptor) to the nucleus of the cell.
This field of study is still developing and gets rather complex when discussing those numerous coregulating factors that regulate at the nuclear level in enhancing transcriptional activity. Their importance in various tissue and their modulation of androgen action is not specifically known. However I believe this area accounts in part for the body's response to exogenously administered hormones in increasing or decreasing or adjusting the intracellular effects across time as a response mechanism.
Androgen/Anabolic Modification
We all understand that with structural modifications to testosterone, the anabolic effects of this androgen can be enhanced. But there is a hypothesis that this can occur natively at the cellular levels depending on the intracellular metabolism of the anabolic steroid in different tissues, with the activity of 5a-reductase being particularly important. As a result of the "altered by metabolism" the anabolic steroid may induce various specific conformational changes of the androgen receptor complex when it binds. This then affects subsequent interaction with various coregulators in different tissues and determine the extent of anabolism. How an anabolic steroid may affect androgen receptor conformation (shape change, strength of binding, degree of activation) and interaction with particular coregulators is not specifically known but may be a way the body determines or fine tunes how hormones will behave in different tissue.
For this to make sense though you need a mental picture of the process of an androgen binding to a receptors and then that complex turning inward into the cell and moving into the nucleus where transcription occurs.
by: DatbTrue
Lets take a look at hormones
In tissue associated with reproduction (such as prostate and seminal vesicles), Testosterone acts as a prohormone and is irreversibly converted by the enzyme 5a-reductase to a more potent androgen 5a-dihydrotestosterone (DHT). 5a-dihydrotestosterone (DHT), is considered more potent because it binds with greater affinity to the androgen receptor (AR) and therefore is strongly androgenic.
In other tissues, such as adipose tissue and parts of the brain, Testosterone is converted by the aromatase enzyme to the hormone estrogen and estradiol which binds to the estrogen receptor.
In bone Testosterone exerts its effect by acting both directly and by aromatizing to estradiol.
In skeletal muscle there is no 5a-reductase activity. Intracellular DHT is very low in skeletal muscle, and its presence is further diminished because of the high activity of the enzyme 3a-hydroxysteroid-dehydrogenase in this tissue (and cardiac tissue as well). This enzyme converts DHT irreversibly to 3a-androstanediol. So in skeletal muscle tissue testosterone itself is primarily binding to the androgen receptor. However aromatase expression and activity is significant and the conversion of testosterone to estrogen is ongoing. It has not yet been determined to what extent if any estrogen plays in mediating some of muscle building effects of androgens but it appears to play a role. In skelelatol muscle it is present and active.
Testosterone and DHT can also be converted to weaker androgens, if the target tissue posses the necessary enzyme activity (i.e. 3a-hydroxysteroid dehydrogenase, 17b-hydroxysteroid dehydrogenase).
Modulators of androgens
The effects of androgens at the molecular level can vary. The events that are engendered by androgens when they bind to an Androgen Receptor can be increased or decreased depending on the distribution of what is known as androgen receptor coregulators. This distribution can vary throughout various tissues and change throughout time. These coregulators are simply proteins that affect the transcriptional activity of the androgen receptor. For example one category of coregulator stabilizes the ligand-bound receptor (i.e. the androgen molecule bound to its receptor) while others facilitate the translocation (or movement) of the ligand-bound receptor (i.e. the androgen molecule bound to its receptor) to the nucleus of the cell.
This field of study is still developing and gets rather complex when discussing those numerous coregulating factors that regulate at the nuclear level in enhancing transcriptional activity. Their importance in various tissue and their modulation of androgen action is not specifically known. However I believe this area accounts in part for the body's response to exogenously administered hormones in increasing or decreasing or adjusting the intracellular effects across time as a response mechanism.
Androgen/Anabolic Modification
We all understand that with structural modifications to testosterone, the anabolic effects of this androgen can be enhanced. But there is a hypothesis that this can occur natively at the cellular levels depending on the intracellular metabolism of the anabolic steroid in different tissues, with the activity of 5a-reductase being particularly important. As a result of the "altered by metabolism" the anabolic steroid may induce various specific conformational changes of the androgen receptor complex when it binds. This then affects subsequent interaction with various coregulators in different tissues and determine the extent of anabolism. How an anabolic steroid may affect androgen receptor conformation (shape change, strength of binding, degree of activation) and interaction with particular coregulators is not specifically known but may be a way the body determines or fine tunes how hormones will behave in different tissue.
For this to make sense though you need a mental picture of the process of an androgen binding to a receptors and then that complex turning inward into the cell and moving into the nucleus where transcription occurs.