Trenbolone – A summary from the article, “Yarrow JF, McCoy SC, Borst SE. Tissue selectivity and potential clinical applications of trenbolone (17[beta]-hydroxyestra-4,9,11-trien-3-one): A potent anabolic steroid with reduced androgenic and estrogenic activity. Steroids;In Press, Accepted Manuscript.”
Androgens exert both genomic and rapid non-genomic actions. The genomic actions primarily occur following classic androgen receptor (AR) mediated signaling pathways. The non-genomic actions are mediated by androgen interaction with cell surface G-protein coupled receptors. Testosterone dose-dependently augments skeletal muscle mass and bone mineral density (BMD), reduces adiposity, and elevates red blood cell production (erythropoiesis) in men either directly, via AR activation, or indirectly, via AR and estradiol receptor (ER) activation, following its conversion to dihydrotestosterone (DHT) and estradiol (E2), respectively.
Many of the side-effects associated with supraphysiological testosterone administration appear to be primarily mediated by the more potent testosterone metabolites, DHT and E2. The metabolism and the biological effects of testosterone are influenced by the tissue-specific localization and expression of the 5alpha reductase isoenzymes and the aromatase enzyme. These considerations have led to the development of selective androgen receptor modulators (SARM), steroidal and non-steroidal, aimed at inducing anabolic effects in skeletal muscle and bone without inducing adverse effects.
17? –TBOH (trenbolone) has a low oral bioavailability (not methylated at the 17? position), it is not a substrate for 5? reductase and may not be a substrate for aromatase. The toxicity of 17? –TBOH has not been scientifically studied in humans, but anecdotally has been reported to have a low potential for liver toxicity because this drug is generally administered intramuscularly.
The metabolism of 17? –TBOH differs from that of testosterone because 17? –TBOH is neither 5? reducible nor aromatizable. The primary metabolites of 17? –TBOH are the less potent androgens 17? –TBOH and Trendione (TBO) in humans. Due to the reduced potency of its metabolites, 17? –TBOH appears to induce fewer systemic and tissue-specific androgenic and estrogenic side-effects than testosterone.
Some variation in the in vivo metabolism of 17? –TBOH exists among mammalian species, but the primary metabolites are 17?-hydroxy- and 17- oxo- metabolites of trenbolone in rodents or 17?-hydroxy- metabolites of trenbolone in ruminants (various hoofed, even-toed, usually horned mammals of the suborder Ruminantia, such as cattle, sheep, goats, deer, and giraffes, characteristically having a stomach divided into four compartments and chewing a cud consisting of regurgitated, partially digested food).
In humans, ingested 6,7-3H labeled 17? –TBOH is primarily excreted intact, as 17? –TBOH, as the 17? epimer (epitrenbolone; 17? –TBOH ) or as trendione (TBO). Several yet to be identified polar metabolites of 17? –TBOH have also been detected in human urine. 17? –TBOH has a greater affinity for the AR than any of its primary metabolites, suggesting that biotransformation of 17? –TBOH reduces the biological activity of this steroid. [Schanzer W. Metabolism of anabolic androgenic steroids. Clin Chem 1996;42(7):1001-20. Link: http://www.clinchem.org/cgi/reprint/42/7/1001.pdf ]
17? –TBOH-acetate (17?-acetoxyestra-4,9,11-trien-3-one) is a highly potent anabolic androgenic steroid which is primarily used legally as a growth promoting agent in domestic livestock production either alone, as Finaplix or in combination with E2, as Revalor, or E2-benzoate, as Synovex. Following administration, 17? –TBOH-acetate is rapidly converted to the biologically active steroid 17? –TBOH.
5? Reductase: Despite its structural similarities to testosterone, 17? –TBOH does not undergo 5? reduction due to the presence of a 3-oxotriene structure, which prevents A ring reduction. 17? –TBOH undergoes biotransformation to less biologically active androgens, similar to other anabolic androgenic steroids, such as 19-nortestosterone.
17? –TBOH administration has been shown to reduce prostate mass in growing male rodents when compared with control animals. 17? –TBOH exerts less pronounced effects than testosterone in androgen-sensitive tissues which express the 5? reductase enzyme including the prostate and accessory sex-organs, despite the fact that 17? –TBOH binds to the human AR, along with ARs of various model species, with approximately three times the affinity of testosterone.
17? –TBOH remains highly anabolic, evidenced by equal or greater growth in the levator ani skeletal muscle (an androgen responsive tissue which lacks the 5? reductase enzymes), compared to testosterone. Reports indicate that 17? –TBOH produces a ratio of anabolic/androgenic effects that may be favorable compared to the effects of testosterone.
Aromatase: 17? –TBOH and other C19 norandrogens are reported to not be substrates for the aromatase enzyme and to be relatively non-estrogenic; although some debate exists regarding 19-nortestosterone to undergo aromatization and induce estrogenic effects. In vitro bioassays and cell culture experiments demonstrate that 17? – TBOH and its metabolites have a very low binding affinity for ERs and have low estrogenic activity with approximately 20% of the efficacy of E2. Reports also suggest that 17? – TBOH reduces serum E2 concentrations in vivo and exerts a variety of anti-estrogenic effects, perhaps through hypothalamic feedback inhibition of the production of testosterone (a substrate necessary for endogenous E2 biosynthesis).
Body Growth/Skeletal Muscle: Trenbolone, 17? –TBOH, a potent synthetic testosterone analogue, promotes gains in skeletal muscle mass and BMD and reduces adiposity in various model species. The use of 17? – TBOH in athletics suggests that this steroid is capable of producing potent anabolic effects in muscle.
The administration of 17? –TBOH or its acetate ester enhance total body growth and skeletal muscle mass in various rodent and livestock models when administered alone or when administered in combination with E2. Several studies have reported that administration of 17? –TBOH in combination with E2 results in greater body growth and skeletal muscle mass than either steroid alone; indicating that E2 enhances the anabolic effects of 17? –TBOH.
The presence of E2 is not required for 17? –TBOH to augment skeletal muscle mass as demonstrated in rodent models which experience significant growth of the levator ani muscle and other skeletal muscles following 17? –TBOH administration, despite lacking the primary source of endogenous E2.
5? reduction of testosterone is not required for skeletal muscle maintenance in hypogonadal animals or humans. E2 administration has been shown to protect against loss of muscle strength in ovariectomized female rodents suggesting that aromatization might contribute to the effects of testosterone on skeletal muscle in males.
The anabolic responses appear to be related to the direct activation of tissue-specific AR mediated signaling pathways, alterations in endogenous growth factors, and reductions in glucocorticoid activity.
Human myonuclei are approximately 50% AR positive and ruminants are highly sensitive to androgen induced myotropic stimuli due to high concentrations of ARs in bovine skeletal muscle and skeletal muscle satellite cells. The androgen sensitive levator ani muscle in rodents contains approximately 74% AR positive myonuclei and experiences robust atrophic responses to castration and hypertrophic responses to androgen administration.
It is suspected that 17? –TBOH exerts direct anabolic effects on skeletal muscle primarily via AR activation and associated nuclear translocation and transcription or via modulation of the Wnt/?-catenin pathway, similar to other androgens. In vitro evidence indicates that 17? –TBOH induces translocation of human ARs to the nucleus in a dose-dependent manner and induces gene transcription to at least the same extent as DHT. 17? –TBOH treatment of cultured bovine satellite cells upregulates AR mRNA expression.
17? –TBOH may induce anabolic effects via mechanisms associated with alterations in endogenous growth factor concentrations or the responsiveness of skeletal muscle to such growth factors. 17? –TBOH alone or in combination with 17? –E2 upregulates insulin-like growth factor (IGF-1) mRNA in a variety of tissues. The upregulation of IGF-1 mRNA translates into increased serum IGF-1 in 17? –TBOH treated animals. It seems likely that increased growth factor expression resulting from 17? –TBOH administration is one mechanism underlying the anabolic responses to this steroid in skeletal muscle, especially considering that binding of IGF-1 to the type 1 IGF receptor is required for proliferation of satellite cells.
17? –TBOH may also preserve or increase lean mass by reducing via anti-catabolic effects associated with reductions in endogenous glucocorticoid activity or with the suppression of amino acid degradation within the liver. 17? –TBOH administration has been shown to reduce circulating corticosterone concentrations in rodents and resting cortisol in cattle. Evidence indicates that 17? –TBOH works in the adrenals to suppress adrenocorticotropic hormone (ACTH)-stimulated cortisol synthesis and to suppress cortisol release.
17? –TBOH has been shown to reduce the ability of cortisol to bind to skeletal muscle glucocorticoid receptors (GR) and to down regulate skeletal muscle GR expression. The multiple anti-glucocorticoid actions induced by 17? –TBOH explain, in part, the 17? –TBOH-mediated increase in total body nitrogen retention and the reductions in total and myofibrillar protein degradation in several species. As a result of its anti-glucocorticoid actions, 17? –TBOH produces a more robust inhibition of protein degradation than does testosterone, which only slightly reduces protein degradation while increasing protein synthesis.
Fat Mass: 17? –TBOH administration alone or in combination with E2 also reduces subcutaneous fat, intramuscular fat, and muscle marbling (a gross measurement of intramuscular fat content), along with other stores of body fat in various livestock species. 17? – TBOH-enanthate administration reduces retroperitoneal fat mass, perirenal fat mass, and perhaps other fat depots, in male rodents in a dose-dependent manner. The lipolytic effects of 17? –TBOH-enanthate appear even more potent than that of supraphysiological testosterone-enanthate.
HPTA: Disruptions of the HPG axis, including reductions in serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, DHT, and E2 have been observed in a variety of species following 17? –TBOH exposure. Indirect evidence indicates disruptions of the HPG axis are present in livestock which experience reduced testicular circumference and weight and delayed puberty following administration of 17? –TBOH.
Erythropoiesis: Testosterone administration results in dose-dependent increases in both hematocrit and hemoglobin. The aromatization of testosterone does not appear to be required for erythropoiesis as administration of DHT (a non-aromatizable endogenous androgen) augments erythropoiesis in men, while exogenous testosterone, but not E2 administration, increases hematocrit in aromatase deficient men. The 5? reduction of testosterone may not be required for erythropoiesis as high-dose testosterone administration in combination with finasteride increases hematocrit and hemoglobin concentrations in hypogonadal men to the same extent as testosterone alone, despite a nearly 65% lower serum DHT concentrations in the finasteride group. The conclusion from these studies is androgens directly elevate erythropoiesis via AR-mediated mechanisms. 17? –TBOH increases hemoglobin concentrations in orchiectomized male rodents in a dose-dependent manner and to a greater extent than supraphysiological testosterone, even though circulating DHT is suppressed by over 50% following 17? –TBOH administration.
Androgens exert both genomic and rapid non-genomic actions. The genomic actions primarily occur following classic androgen receptor (AR) mediated signaling pathways. The non-genomic actions are mediated by androgen interaction with cell surface G-protein coupled receptors. Testosterone dose-dependently augments skeletal muscle mass and bone mineral density (BMD), reduces adiposity, and elevates red blood cell production (erythropoiesis) in men either directly, via AR activation, or indirectly, via AR and estradiol receptor (ER) activation, following its conversion to dihydrotestosterone (DHT) and estradiol (E2), respectively.
Many of the side-effects associated with supraphysiological testosterone administration appear to be primarily mediated by the more potent testosterone metabolites, DHT and E2. The metabolism and the biological effects of testosterone are influenced by the tissue-specific localization and expression of the 5alpha reductase isoenzymes and the aromatase enzyme. These considerations have led to the development of selective androgen receptor modulators (SARM), steroidal and non-steroidal, aimed at inducing anabolic effects in skeletal muscle and bone without inducing adverse effects.
17? –TBOH (trenbolone) has a low oral bioavailability (not methylated at the 17? position), it is not a substrate for 5? reductase and may not be a substrate for aromatase. The toxicity of 17? –TBOH has not been scientifically studied in humans, but anecdotally has been reported to have a low potential for liver toxicity because this drug is generally administered intramuscularly.
The metabolism of 17? –TBOH differs from that of testosterone because 17? –TBOH is neither 5? reducible nor aromatizable. The primary metabolites of 17? –TBOH are the less potent androgens 17? –TBOH and Trendione (TBO) in humans. Due to the reduced potency of its metabolites, 17? –TBOH appears to induce fewer systemic and tissue-specific androgenic and estrogenic side-effects than testosterone.
Some variation in the in vivo metabolism of 17? –TBOH exists among mammalian species, but the primary metabolites are 17?-hydroxy- and 17- oxo- metabolites of trenbolone in rodents or 17?-hydroxy- metabolites of trenbolone in ruminants (various hoofed, even-toed, usually horned mammals of the suborder Ruminantia, such as cattle, sheep, goats, deer, and giraffes, characteristically having a stomach divided into four compartments and chewing a cud consisting of regurgitated, partially digested food).
In humans, ingested 6,7-3H labeled 17? –TBOH is primarily excreted intact, as 17? –TBOH, as the 17? epimer (epitrenbolone; 17? –TBOH ) or as trendione (TBO). Several yet to be identified polar metabolites of 17? –TBOH have also been detected in human urine. 17? –TBOH has a greater affinity for the AR than any of its primary metabolites, suggesting that biotransformation of 17? –TBOH reduces the biological activity of this steroid. [Schanzer W. Metabolism of anabolic androgenic steroids. Clin Chem 1996;42(7):1001-20. Link: http://www.clinchem.org/cgi/reprint/42/7/1001.pdf ]
17? –TBOH-acetate (17?-acetoxyestra-4,9,11-trien-3-one) is a highly potent anabolic androgenic steroid which is primarily used legally as a growth promoting agent in domestic livestock production either alone, as Finaplix or in combination with E2, as Revalor, or E2-benzoate, as Synovex. Following administration, 17? –TBOH-acetate is rapidly converted to the biologically active steroid 17? –TBOH.
5? Reductase: Despite its structural similarities to testosterone, 17? –TBOH does not undergo 5? reduction due to the presence of a 3-oxotriene structure, which prevents A ring reduction. 17? –TBOH undergoes biotransformation to less biologically active androgens, similar to other anabolic androgenic steroids, such as 19-nortestosterone.
17? –TBOH administration has been shown to reduce prostate mass in growing male rodents when compared with control animals. 17? –TBOH exerts less pronounced effects than testosterone in androgen-sensitive tissues which express the 5? reductase enzyme including the prostate and accessory sex-organs, despite the fact that 17? –TBOH binds to the human AR, along with ARs of various model species, with approximately three times the affinity of testosterone.
17? –TBOH remains highly anabolic, evidenced by equal or greater growth in the levator ani skeletal muscle (an androgen responsive tissue which lacks the 5? reductase enzymes), compared to testosterone. Reports indicate that 17? –TBOH produces a ratio of anabolic/androgenic effects that may be favorable compared to the effects of testosterone.
Aromatase: 17? –TBOH and other C19 norandrogens are reported to not be substrates for the aromatase enzyme and to be relatively non-estrogenic; although some debate exists regarding 19-nortestosterone to undergo aromatization and induce estrogenic effects. In vitro bioassays and cell culture experiments demonstrate that 17? – TBOH and its metabolites have a very low binding affinity for ERs and have low estrogenic activity with approximately 20% of the efficacy of E2. Reports also suggest that 17? – TBOH reduces serum E2 concentrations in vivo and exerts a variety of anti-estrogenic effects, perhaps through hypothalamic feedback inhibition of the production of testosterone (a substrate necessary for endogenous E2 biosynthesis).
Body Growth/Skeletal Muscle: Trenbolone, 17? –TBOH, a potent synthetic testosterone analogue, promotes gains in skeletal muscle mass and BMD and reduces adiposity in various model species. The use of 17? – TBOH in athletics suggests that this steroid is capable of producing potent anabolic effects in muscle.
The administration of 17? –TBOH or its acetate ester enhance total body growth and skeletal muscle mass in various rodent and livestock models when administered alone or when administered in combination with E2. Several studies have reported that administration of 17? –TBOH in combination with E2 results in greater body growth and skeletal muscle mass than either steroid alone; indicating that E2 enhances the anabolic effects of 17? –TBOH.
The presence of E2 is not required for 17? –TBOH to augment skeletal muscle mass as demonstrated in rodent models which experience significant growth of the levator ani muscle and other skeletal muscles following 17? –TBOH administration, despite lacking the primary source of endogenous E2.
5? reduction of testosterone is not required for skeletal muscle maintenance in hypogonadal animals or humans. E2 administration has been shown to protect against loss of muscle strength in ovariectomized female rodents suggesting that aromatization might contribute to the effects of testosterone on skeletal muscle in males.
The anabolic responses appear to be related to the direct activation of tissue-specific AR mediated signaling pathways, alterations in endogenous growth factors, and reductions in glucocorticoid activity.
Human myonuclei are approximately 50% AR positive and ruminants are highly sensitive to androgen induced myotropic stimuli due to high concentrations of ARs in bovine skeletal muscle and skeletal muscle satellite cells. The androgen sensitive levator ani muscle in rodents contains approximately 74% AR positive myonuclei and experiences robust atrophic responses to castration and hypertrophic responses to androgen administration.
It is suspected that 17? –TBOH exerts direct anabolic effects on skeletal muscle primarily via AR activation and associated nuclear translocation and transcription or via modulation of the Wnt/?-catenin pathway, similar to other androgens. In vitro evidence indicates that 17? –TBOH induces translocation of human ARs to the nucleus in a dose-dependent manner and induces gene transcription to at least the same extent as DHT. 17? –TBOH treatment of cultured bovine satellite cells upregulates AR mRNA expression.
17? –TBOH may induce anabolic effects via mechanisms associated with alterations in endogenous growth factor concentrations or the responsiveness of skeletal muscle to such growth factors. 17? –TBOH alone or in combination with 17? –E2 upregulates insulin-like growth factor (IGF-1) mRNA in a variety of tissues. The upregulation of IGF-1 mRNA translates into increased serum IGF-1 in 17? –TBOH treated animals. It seems likely that increased growth factor expression resulting from 17? –TBOH administration is one mechanism underlying the anabolic responses to this steroid in skeletal muscle, especially considering that binding of IGF-1 to the type 1 IGF receptor is required for proliferation of satellite cells.
17? –TBOH may also preserve or increase lean mass by reducing via anti-catabolic effects associated with reductions in endogenous glucocorticoid activity or with the suppression of amino acid degradation within the liver. 17? –TBOH administration has been shown to reduce circulating corticosterone concentrations in rodents and resting cortisol in cattle. Evidence indicates that 17? –TBOH works in the adrenals to suppress adrenocorticotropic hormone (ACTH)-stimulated cortisol synthesis and to suppress cortisol release.
17? –TBOH has been shown to reduce the ability of cortisol to bind to skeletal muscle glucocorticoid receptors (GR) and to down regulate skeletal muscle GR expression. The multiple anti-glucocorticoid actions induced by 17? –TBOH explain, in part, the 17? –TBOH-mediated increase in total body nitrogen retention and the reductions in total and myofibrillar protein degradation in several species. As a result of its anti-glucocorticoid actions, 17? –TBOH produces a more robust inhibition of protein degradation than does testosterone, which only slightly reduces protein degradation while increasing protein synthesis.
Fat Mass: 17? –TBOH administration alone or in combination with E2 also reduces subcutaneous fat, intramuscular fat, and muscle marbling (a gross measurement of intramuscular fat content), along with other stores of body fat in various livestock species. 17? – TBOH-enanthate administration reduces retroperitoneal fat mass, perirenal fat mass, and perhaps other fat depots, in male rodents in a dose-dependent manner. The lipolytic effects of 17? –TBOH-enanthate appear even more potent than that of supraphysiological testosterone-enanthate.
HPTA: Disruptions of the HPG axis, including reductions in serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, DHT, and E2 have been observed in a variety of species following 17? –TBOH exposure. Indirect evidence indicates disruptions of the HPG axis are present in livestock which experience reduced testicular circumference and weight and delayed puberty following administration of 17? –TBOH.
Erythropoiesis: Testosterone administration results in dose-dependent increases in both hematocrit and hemoglobin. The aromatization of testosterone does not appear to be required for erythropoiesis as administration of DHT (a non-aromatizable endogenous androgen) augments erythropoiesis in men, while exogenous testosterone, but not E2 administration, increases hematocrit in aromatase deficient men. The 5? reduction of testosterone may not be required for erythropoiesis as high-dose testosterone administration in combination with finasteride increases hematocrit and hemoglobin concentrations in hypogonadal men to the same extent as testosterone alone, despite a nearly 65% lower serum DHT concentrations in the finasteride group. The conclusion from these studies is androgens directly elevate erythropoiesis via AR-mediated mechanisms. 17? –TBOH increases hemoglobin concentrations in orchiectomized male rodents in a dose-dependent manner and to a greater extent than supraphysiological testosterone, even though circulating DHT is suppressed by over 50% following 17? –TBOH administration.
Last edited:
opcorn: be great if tren attained clinical viability and usage...
Just found the Bill Roberts profile. Also found basskilleronline in my googling. Have to give that a look too.
