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An approach to the anabolic action of androgens by an experimental system.

Abstract

As skeletal muscle is more developed in the male than in the female, it is supposed that androgens might be responsible for myotrophic or anabolic action. In this respect, many studies were made to try to answer the question: are androgens (or some of their metabolites) responsible for myotrophic action and by what mechanism? Do they act directly on skeletal muscle as on other target organs, or have they an indirect action on muscle, perhaps through a secondary stimulant (for instance synthesized in the liver)? Evidence is now presented that, in the rat's skeletal muscle, androgens likely act through the binding to a cytosoluble receptor, as they do in the ventral prostate. This receptor has analogous properties to all other androgen receptors. It is a proteinaceous (pronase sensible) "8S" component binding testosterone and androstanolone with high affinity and small capacity; it does not bind androstanediols. This finding and the increased incorporation of 3H-thymidine in nuclei and increased protein synthesis obtained in muscle cell culture after action of testosterone favour the concept that muscular cells are direct targets of androgens in skeletal muscles. Presently, the steroid specificity of receptor binding cannot be assessed quantitatively with crude cytosol preparation. While in ventral prostate, androstanolone has a higher affinity, the binding experiments have not yet indicated in muscle if the higher affinity of testosterone is related to differential binding of the two steroids, or to the complex effects of enzymes present in the extracts. In fact, evidence was obtained for 5alpha-reductase and 3alpha,beta-hydroxysteroid reductase activities under the same experimental conditions as for binding determinations. Therefore, the apparent antrostanolone binding in muscle could be lowered by transformation into androstanediols not binding to receptor, or the increase of apparent testosterone binding due to transformation into androstanolone. So the problem of whether testosterone or androstanolone or another natural steroid is the most effective myotrophic hormone in rat skeletal muscle remains unsolved. However, this animal model allows the study of certain interesting aspects of action of androgens on muscle. When receptor preparations are partially purified and not contaminated by metabolizing enzymes, different natural or synthetic steroids can be tested as to their affinity and anabolic effectiveness in muscle. It would be of pharmacological interest if receptor diversity made it possible to distinguish myotrophic action from virilizing activities. This in vitro system allows studying the mechanism of action of molecules which could have in vivo an anti-androgen effect and it is remarkable that radioactive testosterone and androstanolone can compete for receptor binding by an excess of estradiol, progesterone and cyproterone acetate...

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

182485

Citation

Michel, G, and E E. Baulieu. "An Approach to the Anabolic Action of Androgens By an Experimental System." Environmental Quality and Safety. Supplement, 1976, pp. 54-9.
Michel G, Baulieu EE. An approach to the anabolic action of androgens by an experimental system. Environ Qual Saf Suppl. 1976.
Michel, G., & Baulieu, E. E. (1976). An approach to the anabolic action of androgens by an experimental system. Environmental Quality and Safety. Supplement, (5), 54-9.
Michel G, Baulieu EE. An Approach to the Anabolic Action of Androgens By an Experimental System. Environ Qual Saf Suppl. 1976;(5)54-9. PubMed PMID: 182485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An approach to the anabolic action of androgens by an experimental system. AU - Michel,G, AU - Baulieu,E E, PY - 1976/1/1/pubmed PY - 1976/1/1/medline PY - 1976/1/1/entrez SP - 54 EP - 9 JF - Environmental quality and safety. Supplement JO - Environ Qual Saf Suppl IS - 5 N2 - As skeletal muscle is more developed in the male than in the female, it is supposed that androgens might be responsible for myotrophic or anabolic action. In this respect, many studies were made to try to answer the question: are androgens (or some of their metabolites) responsible for myotrophic action and by what mechanism? Do they act directly on skeletal muscle as on other target organs, or have they an indirect action on muscle, perhaps through a secondary stimulant (for instance synthesized in the liver)? Evidence is now presented that, in the rat's skeletal muscle, androgens likely act through the binding to a cytosoluble receptor, as they do in the ventral prostate. This receptor has analogous properties to all other androgen receptors. It is a proteinaceous (pronase sensible) "8S" component binding testosterone and androstanolone with high affinity and small capacity; it does not bind androstanediols. This finding and the increased incorporation of 3H-thymidine in nuclei and increased protein synthesis obtained in muscle cell culture after action of testosterone favour the concept that muscular cells are direct targets of androgens in skeletal muscles. Presently, the steroid specificity of receptor binding cannot be assessed quantitatively with crude cytosol preparation. While in ventral prostate, androstanolone has a higher affinity, the binding experiments have not yet indicated in muscle if the higher affinity of testosterone is related to differential binding of the two steroids, or to the complex effects of enzymes present in the extracts. In fact, evidence was obtained for 5alpha-reductase and 3alpha,beta-hydroxysteroid reductase activities under the same experimental conditions as for binding determinations. Therefore, the apparent antrostanolone binding in muscle could be lowered by transformation into androstanediols not binding to receptor, or the increase of apparent testosterone binding due to transformation into androstanolone. So the problem of whether testosterone or androstanolone or another natural steroid is the most effective myotrophic hormone in rat skeletal muscle remains unsolved. However, this animal model allows the study of certain interesting aspects of action of androgens on muscle. When receptor preparations are partially purified and not contaminated by metabolizing enzymes, different natural or synthetic steroids can be tested as to their affinity and anabolic effectiveness in muscle. It would be of pharmacological interest if receptor diversity made it possible to distinguish myotrophic action from virilizing activities. This in vitro system allows studying the mechanism of action of molecules which could have in vivo an anti-androgen effect and it is remarkable that radioactive testosterone and androstanolone can compete for receptor binding by an excess of estradiol, progesterone and cyproterone acetate... SN - 0340-4714 UR - https://www.unboundmedicine.com/medline/citation/182485/An_approach_to_the_anabolic_action_of_androgens_by_an_experimental_system_ L2 - https://medlineplus.gov/anabolicsteroids.html DB - PRIME DP - Unbound Medicine ER -