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BACKGROUND: Stretching of skeletal muscle induces expression of the genes which encode myogenic transcription factors or muscle contractile proteins and results in muscle growth. Anabolic steroids are reported to strengthen muscles. We have previously studied the effects of muscle stretching on gene expression. Here, we studied the effect of a combination of passive stretching and the administration of an anabolic steroid on mRNA expression of a muscle growth factor, insulin-like growth factor-I autocrine variant, or mechano-growth factor (MGF). METHODS: Twelve 8-week-old male Wistar rats were used. Metenolone was administered and passive repetitive dorsiflexion and plantar flexion of the ankle joint performed under deep anesthesia. After 24 h, the gastrocnemius muscles were removed and the mRNA expression of insulin-like growth factor-I autocrine variant was measured using quantitative real-time polymerase chain reaction. RESULTS: Repetitive stretching in combination with metenolone, but not stretching alone, significantly increased MGF mRNA expression. CONCLUSION: Anabolic steroids enhance the effect of passive stretching on MGF expression in skeletal muscle.

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Androgen inhibits osteoclastic bone resorption with increase of bone formation through androgen receptor in bone tissue. Anabolic steroids are synthetic derivates of testoterone. Anobolic steroids have favorable anabolic actions, lessening virilizing effects. Several anabolic steroids have been synthesized and some of them have been approved as a drug for anti osteoporosis. Anabolic steroids have revealed the increased bone mineral content or bone mineral density at the radius, and the lumbar spine in osteoporosis patients. Anabolic steroids have also decreased fat mass with increase of lean body mass and muscle mass, and lessened bone pain in osteoporosis patients having bone fracture, which seem to be favorable effects for especially elder osteoporosis patients. But in recent years the number of osteoporosis patients treated with anabolic steroids has been decreasing. Furthermore recently few clinical trials about the effect of anabolic steroids on osteoporosis have been reported, and prospective study for bone fracture using anabolic steroids has not reported yet. We would like to expect additional effects except on bone formation will enhance the frequency in use of anabolic steroids, and the prospective clinical study about the prevention against bone fracture will be reported in the future.

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Many athletes use drugs, especially anabolic androgenic steroids (AAS), but there are few reports on the endocrinological and pathological changes in AAS abusers. In this study we reported the results of endocrinological examinations in rats administered AAS and also physical changes. We separated 37 male Wistar rats (7 weeks old) into 3 groups: Group A was medicated with nandrolone decanoate, metenolone acetate, and dromostanolone; Group B with nandrolone decanoate and saline; and Group C was given only saline. They were given subcutaneous injections of the medications or the control vehicle once a week for 6 weeks. Medications were stopped for 4 weeks, and then resumed for another 6 weeks. After that, rats were sacrificed. Serum testosterone level in Group A was significantly higher than that in Group C. Serum dihydrotestosterone in Group A was significantly higher than that in both Groups B and C. Serum estradiol-17beta levels in Groups A and B were significantly higher than that in Group C. In pathological evaluation, heart, testis, and adrenal gland were severely damaged. These findings indicate that there is a high degree of risk related to the use of AAS.

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Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.

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The loss of force and mass in the conditioned latissimus dorsi muscle are principal reasons for the poor improvement in hemodynamic functioning attained by cardiomyoplasty. Using 24 sheep, we investigated the effect of anabolic steroids on the hemodynamic, histologic, and myophysiologic characteristics in the setting of cardiomyoplasty. In 12 of the animals (group A), the latissimus dorsi muscles were electrically conditioned with an Itrel pulse generator; in the remaining 12 animals (group B), the electrical conditioning was combined with the administration of an anabolic hormone (metenolone; 100 mg/week). The hemodynamic measurements were performed during isolated perfusion of the subclavian artery (maintenance of pressure in the muscles), while all other circulation variables were held at the exact and reproducible value of zero by inducing ventricular fibrillation. Maximum force and muscle mass showed a significant increase in group B (maximum force: group A, 4.23 +/- 0.55 kp, and group B, 6.0 +/- 3.14 kp; muscle mass: group A, +11.07% +/- 1.06%, and group B, +79.9% +/- 40.8%). The ratio of type I to type II fibers after 12 weeks was 65.2% to 34.8% in group A and 96.7% to 3.3% in group B, as opposed to 19.9% to 80.1% in the control group. No side effects of the anabolic steroids were observed during the experiment. In the hemodynamic studies, we were able to demonstrate a further significant increase in the left ventricular pressure, fractional fiber shortening value, ejection fraction, stroke volume, cardiac output, and stroke work when using conditioned latissimus dorsi muscles that were additionally treated with metenolone.(ABSTRACT TRUNCATED AT 250 WORDS)

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In 12 sheep the left latissimus dorsi muscles (LD) were conditioned by chronic electrostimulation with a pulse generator (Itrel, Medtronic). Six animals (group B) received a weekly intramuscular injection of an anabolic steroid (Metenolon). After 14 weeks the contraction parameters of the left LDs (group A and B) and right LDs (control group) were investigated. The increase in weight of the conditioned LDs was 11.07% (+/- 1.06%) in group A and 79.97% (+/- 40.8; P < 0.05) in group B. The force capacity under stimulation patterns which were just tetanic was 1.15 kp in group A and 4.13 kp in group B (P < 0.05); under supramaximal stimulation patterns it was 4.23 kp (A) and 6.0 kp (B) (P = ns). The force time relation (dF/dt) was 6.7 kp/s for the left LDs in group A versus 16.4 kp/s for the right LDs (P < 0.01); in group B it was 5.13 kp/s for the left LDs versus 15.8 kp/s for the control muscles (P < 0.05). The maximal force (Fmax) per 100 g muscle weight did not differ significantly (A: 2.42 kp/100 g; B: 2.52 kp/100 g). In conclusion, the LD muscles which were subjected to both anabolic therapy and electrical stimulation showed a significant increase in their force capacity due to an enormous increase in mass. Fibre type transformation was complete only in group B. No fibre deterioration was observable in either group. No anabolic side effects were detected in the animals. With the use of anabolic steroids, therefore, a clearer direct increase in contractility on the left ventricle should be expected ("squeezing" theory), as well as a contribution to reduction in wall tension and myocardial oxygen consumption, respectively, according to Laplace's Law (via the considerable increase in thickness).

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A randomized blind prospective study was carried out to determine if an anabolic androgenic steroid with a high anabolic/androgenic ratio, Group A, (1/0.05) methenolone enanthate (me), compared to an anabolic/androgenic agent with a low anabolic/androgenic ratio, Group B, (1.0/1.0) testosterone propionate (tp), compared to a control, Group C, cottonseed oil (co), affected midhumeral osteotomy healing in 100 two-month-old female Wistar rats. The rats received 4 mg/kg me, 4 mg/kg te, and equal volumes of co weekly. The rats were sacrificed at 2, 4, and 6 weeks. The entire humerus with the healing osteotomy was carefully dissected until all soft tissue attachments were stripped. The healing callus was then subjected to (1) biochemical analysis (hexosamine, hydroxyproline, and calcium), (2) biomechanical testing (progressive distraction of the callus at 1 mm/min on an electrohydraulic materials test system, model 1331, Instron Corp, Canton, MA, and (3) histology. Results of the biochemical testing demonstrated that the percentage of calcium in the healing callus at 2 weeks in group B (tp) was 7.3 +/- 1.0, and this value was greater than that in group C (co), 4.8 +/- 1.6 (p greater than .01), and greater than that in group A (me), 5.6 +/- 0.6 (p greater than .01). At 4 weeks, the percentage of calcium in the callus in group B (tp) was 6.8 +/- 1.9, in group A (me) 7.3 +/- 3.7, and these values were both greater than that in group C (co), 3.9 +/- 2.2 (p greater than .02 and .01, respectively). At 6 weeks the percentage of calcium in the callus in group B (tp) was 11.7 +/- 3.9 and in group A (me) 12.7 +/- 3.9, and again these values were both greater than that in group C (co), 6.7 +/- 2.6 (p greater than .02 and .01, respectively). The remainder of the biochemical analysis, hexosamine and hydroxyproline content, did not show a statistical difference in groups A, B, and C at 2, 4, and 6 weeks. The biomechanical studies and histology also failed to show statistical differences between the three groups at 2, 4, and 6 weeks. The conclusion of this study is that an agent with a low androgenic activity does not increase calcium callus concentrations early in the course of fracture healing compared to an agent with higher androgenic activity. As healing progresses, both agents increase the concentration of calcium in osteotomy healing. The clinical significance of this study is that agents with low androgenic activities favorably influence osteotomy healing and may be clinically useful because they lack unwanted virilizing activity.

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This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.

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The effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three alpha-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-alpha-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma alpha2-macroglobulin. The effect on plasma alpha1-antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-alpha-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.

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Human malignant tumors have been shown to be highly resistant to the chemotherapeutic agents so far available. Since these have to be administered in high doses, hematotoxic effects occur frequently during such treatment. Androgens and anabolic steroids being potent stimulators of normal and of some forms of impaired erythropoiesis, studies were initiated in rats to assess the possibility of a protective role of these steroids against the toxicity of cyclophosphamide. The following results were obtained: 1. A single dose of cyclophosphamide (100 mg/kg) significantly lowered the erythrocyte, reticulocyte, hemoglobin, leucocyte and platelet counts. 2. An initial treatment with nandrolone phenylpropionate signifiantly reduced the decrease of both the erythrocyte and the hemoglobin counts. 3. An initial treatment with metenolone enanthate (Primobolan-Depot) completely prevented the reduction of erythrocytes in appropriate experimental conditions and significantly reduced the decrease of hemoglobins. 4. There was no effect of these steroids on the drop of granulocytes, lymphocytes and platelets. These observations suggest that combination of anabolic steroid therapy with cyclophosphamide therapy may be worthy of clinical trial in patients whose tumors are not subject to growth stimulation by androgenic steroids.

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