Non-Suitability of Levator Ani Method as an Index of Anabolic Effect of Steroids

Nimni, M. E.; Geiger, E.

doi:10.3181/00379727-94-23025

Cited by 23 publications

(4 citation statements)

References 1 publication

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“… Kruskemper (1968) discusses the many failings of the procedures used for determining the myotrophic–androgenic index, for example, the seminal vesicles react more slowly to certain androgens, so that with short test administration, distortions can arise in favour of the myotrophic effect. The harshest criticism of this index was given by Nimni and Geiger (1957) , Scow and Hagan (1957) and Hayes (1965) . Testosterone administration for 56 days to young gonadectomized rats (castrated at 20–23 days of age) had no effect on the growth of the thigh muscle compared with controls, yet there was considerable growth in the perineal musculature ( Scow, 1952 ; Scow and Hagan, 1957 ).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Pharmacology of anabolic steroids

Kicman

2008

British J Pharmacology

488

428

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Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

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Section: Mechanisms Of Actionmentioning

confidence: 99%

Pharmacology of anabolic steroids

Kicman

2008

British J Pharmacology

488

428

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“…The rat levator ani muscle is in fact the dorsal bulbocavernosus muscle, which is peculiar to rodents, and which does not correspond to the levator ani muscle in man, cat, or dog (25). It is trophically dependent (not only sensitive) on androgens (26)(27)(28)(29)(30)(31), and its androgen receptor concentration is intermediate to those of accessory sex tissues and skeletal muscle, respectively (see e.g. Ref.…”

mentioning

confidence: 98%

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*

1984

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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; 17 beta-hydroxy-17 alpha-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. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-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 greater than 19-nortestosterone ( NorT ; nandrolone) greater than methenolone (17 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3-one) greater than testosterone (T) greater than 1 alpha-methyl-DHT]. In other cases, AR binding was weak (RBA values less than 0.05): stanozolol (17 alpha-methyl-5 alpha- androstano [3,2-c]pyrazol-17 beta-ol), methanedienone (17 beta-hydroxy-17 alpha-methyl-1,4-androstadien-3-one), and fluoxymesterolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one) and ethylestrenol (17 alpha-ethyl-4- estren -17 beta-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 [5 alpha-androstane-3 alpha, 17 beta-diol and its 3 beta-isomer (3 alpha- and 3 beta-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (1 alpha-methyl-DHT much greater than DHT greater than T greater than 3 beta-adiol greater than 3 alpha-adiol = 17 alpha-methyl-T greater than methenolone greater than methanedienone greater than 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.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The usual assay for the anabolic potency of steroids is based on changes in the weight of the levator ani muscle of castrated rats (Dorfman, 1962), but this assay has been criticized both because this appears to be a rather specialized tissue reflecting both general anabolic effects and specific sex-linked effects (Nimni & Geiger, 1957; 523…”

Section: Discussionmentioning

confidence: 99%

Response of the Submandibular Gland of the Castrated Mouse to Local and Systemic Administration of Steroids

Brown-Grant¹,

Taylor²

1963

Journal of Endocrinology

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The effects of testosterone propionate (TP) and of 17\g=a\-ethyl-19 nor-testo\x=req-\ sterone (ENT) on the submandibular glands, levator ani muscles and seminal vesicles of castrated mice have been compared. ENT restores submandibular weight and histology about as well as TP but has less effect on the levator ani muscle and much less effect on the seminal vesicles.Both steroids can act directly on the submandibular gland. It is suggested that the effect on the gland may be an indication of the 'anabolic' rather than the 'androgenic' potency of the steroids, and the possible use of this response for the assay of 'anabolic' steroids is discussed.A sexual dimorphism of the submandibular glands of mice was reported by Lacassagne (1940 a, b), and subsequent work has indicated that testosterone is in part responsible for the greater size and the more prominent development of the con¬ voluted granular tubules (serous tubules) of the male gland. Castration results in atrophy of the gland due to regression of the tubules but quite similar histological changes are produced by thyroidectomy. The effects of hypophysectomy are more completely reversed by the administration of thyroxine and testosterone together than by either alone (Grad & Leblond, 1949;Shafer & Muhler, 1960; Burgen & Emmelin, 1961). The changes produced by testosterone have been referred to as a ' masculinization ' of the gland, and it has been claimed that histological changes in the gland are a more sensitive index of androgen secretion than changes in seminal vesicle weight or histological structure (Frantz & Kirschbaum, 1949). In view of the effects of thyroidectomy and thyroxine administration, it seemed that the effect of testosterone might be related more to its metabolic action than to a specific ' mascu¬ linizing ' effect and that it was perhaps unwise to regard submandibular gland changes as a specific and sensitive index of androgen secretion. We have therefore compared the effects on the glands of castrated mice of different doses of testosterone propionate (TP) and 17 oc-ethyl-19 nor-testosterone (ENT). The latter compound is a synthetic steroid said to be as potent as testosterone in anabolic (levator ani) assays but only about one-tenth as potent in androgenic (seminal vesicle and ventral prostate) assays in castrated rats (Saunders & Drill, 1957).

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Non-Suitability of Levator Ani Method as an Index of Anabolic Effect of Steroids

Cited by 23 publications

References 1 publication

Pharmacology of anabolic steroids

Pharmacology of anabolic steroids

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*

Response of the Submandibular Gland of the Castrated Mouse to Local and Systemic Administration of Steroids

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