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Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the... Abstract It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17β-hydroxy-17α-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. lα-Methyl-5α-dihydrotestosterone (lα-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [RBAs relative to that of MT: MT > 19-nortestosterone (NorT; nandrolone) > methenolone (17β-hydroxy-l-methyl-5α-androst-l-en-3-one) > testosterone (T) > lα-methyl-DHT]. In other cases, AR binding was weak (RBA values < 0.05): stanozolol (17α-methyl-5α-androstano[3,2-c]pyrazol-17β-ol), methanedienone (17β-hydroxy-17α-methyl-l,4-androstadien-3-one), and fluoxymesterolone (9α-fluoro-11β-hydroxy-17α-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17β-hydroxy-2-hydroxymethylene-17α-methyl-5α-androstan-3-one) and ethylestrenol (17α-ethyl-4-estren-17β-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5α-androstane-3α,17β-diol and its 3β-isomer (3α- and 3β-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (lα-methyl-DHT >> DHT > T > 3β-adiol > 3α-adiol = 17α-methyl-T > methenolone > methanedienone > stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases. The present data indicate that 1) the existence of a putative anabolic receptor distinct from the AR must be questioned, 2) many anabolic steroids interact with the AR (generally with lower RBA than NorT or T), 3) some steroids with anabolic-androgenic activity in vivo do not bind to the AR, and must have an indirect mechanism of action (e.g. via biotransformation to active compounds, by influencing the metabolism of other steroids, or by displacing them from SHBG). (Endocrinology114: 2100, 1984) This content is only available as a PDF. Author notes * To whom correspondence and requests for reprints should be addressed. † Nyberg, L., E. Dahlberg, K. Lundström, P. Jonsson, and L.-E. Edqvist, submitted for publication. Copyright © 1984 by The Endocrine Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Endocrinology Oxford University Press

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin

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Publisher
Oxford University Press
Copyright
Copyright © 1984 by The Endocrine Society
ISSN
0013-7227
eISSN
1945-7170
DOI
10.1210/endo-114-6-2100
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Abstract

Abstract It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17β-hydroxy-17α-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. lα-Methyl-5α-dihydrotestosterone (lα-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [RBAs relative to that of MT: MT > 19-nortestosterone (NorT; nandrolone) > methenolone (17β-hydroxy-l-methyl-5α-androst-l-en-3-one) > testosterone (T) > lα-methyl-DHT]. In other cases, AR binding was weak (RBA values < 0.05): stanozolol (17α-methyl-5α-androstano[3,2-c]pyrazol-17β-ol), methanedienone (17β-hydroxy-17α-methyl-l,4-androstadien-3-one), and fluoxymesterolone (9α-fluoro-11β-hydroxy-17α-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17β-hydroxy-2-hydroxymethylene-17α-methyl-5α-androstan-3-one) and ethylestrenol (17α-ethyl-4-estren-17β-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5α-androstane-3α,17β-diol and its 3β-isomer (3α- and 3β-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (lα-methyl-DHT >> DHT > T > 3β-adiol > 3α-adiol = 17α-methyl-T > methenolone > methanedienone > stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases. The present data indicate that 1) the existence of a putative anabolic receptor distinct from the AR must be questioned, 2) many anabolic steroids interact with the AR (generally with lower RBA than NorT or T), 3) some steroids with anabolic-androgenic activity in vivo do not bind to the AR, and must have an indirect mechanism of action (e.g. via biotransformation to active compounds, by influencing the metabolism of other steroids, or by displacing them from SHBG). (Endocrinology114: 2100, 1984) This content is only available as a PDF. Author notes * To whom correspondence and requests for reprints should be addressed. † Nyberg, L., E. Dahlberg, K. Lundström, P. Jonsson, and L.-E. Edqvist, submitted for publication. Copyright © 1984 by The Endocrine Society

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Endocrinology – Oxford University Press

Published: Jun 1, 1984

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