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Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle.

The purpose of this study was to ascertain whether anabolic steroids act synergistically with functional overload in terms of increasing muscle weight and subcellular protein content of normal overloaded and suspended overloaded rodent plantaris muscle. Female rats were randomly assigned to six groups (7 rats/group) for 6 wk: 1) normal control (NC), 2) overload (OV), 3) overload steroid (OV-S), 4) normal suspended (N-SUS), 5) overload suspended (OV-SUS), and 6) overload suspended steroid (OV-SUS-S). Rats receiving anabolic steroid were administered 0.3 mg nandrolone decanoate (Deca-Durabolin) per day. Relative to control values, overload induced 1) sparing of muscle weight of the OV-SUS group as well as larger absolute and normalized (mg muscle/g body wt) muscle weight of the OV group (P less than 0.05), 2) greater protein content (mg/muscle, P less than 0.05), and 3) an increased relative expression of slow myosin in both the OV and OV-SUS groups (P less than 0.05). Although anabolic steroid treatment of overload animals (OV-S) did not alter further the pattern of response of any parameter analyzed for the OV group, it did induce larger absolute and normalized muscle weight (P less than 0.05) as well as a greater protein content (mg/muscle, P less than 0.05) of the OV-SUS-S group compared with control values. However, anabolic steroid treatment did not alter the pattern of isomyosin expression observed in the overload (OV-S vs. OV) or overload suspended (OV-SUS-S vs. OV-SUS) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of anabolic steroids on new fiber formation and fiber area during stretch-overload.

The efficacy of anabolic steroid treatment to increase the extent of overload-induced new fiber formation and fiber hypertrophy was examined in anterior latissimus dorsi (ALD) muscles of Japanese quails. Adult quails were assigned to a control group (n = 20), which received stretch but no steroid (NS), or a stretch+steroid group (S), which received either nandrolone decanoate (n = 20) or testosterone enanthate (n = 12). Steroids were administered at 4.0 mg.kg body wt-1 x day-1. A weight corresponding to 10% of each bird's body weight was added to the right wing to effect a stretch of the right ALD. Thirty days of stretch-overload resulted in a 145.3 and 143.1% increase in total muscle weight of NS and S groups, respectively. Stretch-induced increases in nonmuscle tissue, fiber length, and new fiber formation were not altered by steroid administration. These results indicate that anabolic steroids did not act synergistically to enhance the extent of fiber hypertrophy or new fiber formation after 30 days of stretch-overload.

Anabolic Agents↗

Anabolic steroids in part reverse glucocorticoid-induced alterations in rat diaphragm.

Animal and clinical studies have shown respiratory muscle dysfunction caused by treatment with glucocorticoids. The present study was designed to investigate whether anabolic steroids are able to antagonize the loss of diaphragm force induced by long-term low-dose methylprednisolone (MP) administration. Male adult rats were randomized to receive saline or MP (0.2 mg . kg-1 .day-1 sc) during 9 mo, with or without nandrolone decanoate (ND; 1 mg . kg-1 . wm -1 im) during the last 3 mo. The approximately 10% reduction in force generation of isolated diaphragm bundles induced by MP was completely abolished by addition of ND. The MP-induced decrease in number of fibers expressing type IIb myosin heavy chains was not reversed by ND. MP slightly reduced type I, IIa, and IIx fiber cross-sectional areas (CSA), but not type IIb fiber CSA. Addition of ND abolished the reduction in IIa and IIx fiber CSA. The MP-induced alterations in glycogenolytic activity and fatty acid oxidation capacity were not reversed by ND. In conclusion, the marked reduction in diaphragm force caused by long-term low-dose MP was completely abolished by addition of ND. ND in part also antagonized the effects of MP on diaphragm morphology but showed no beneficial effects on biochemical changes.

3-Hydroxyacyl CoA Dehydrogenases↗

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI.

Microgravity causes rapid decrement in musculoskeletal mass is associated with a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these losses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 +/- 4.8 vs. 74.5 +/- 3.6 cm3 in the ground control rats; P < 0.001) and had a 5% decrease in bone mineral density (BMD) (P < 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 +/- 3.0 vs. 56 +/- 1.8 cm3 in ground control rats; P < 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 +/- 2 and 51.6 +/- 1.2 cm3, respectively; a 63% improvement; P < 0. 05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 +/- 0.04 vs. 1.04 +/- 0.04 density units in vehicle controls; P < 0.05) and a 76% improvement in the ND group (1.13 +/- 0.07 density units), whereas ground control rats had a BMD of 1.17 +/- 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses.

Anabolic Agents↗

[Effects of diets containing medium-chain and long-chain triacylglycerols in the genetically obese Zucker fa/fa rat. Composition of fatty acids and triacylglycerols of the liver and adipose tissues].

The effects of a hyperlipidic diet containing medium-chain triacylglycerols (MCT) or long-chain triacylglycerols (LCT) and a control diet on the lipid composition of liver and adipose tissue in the Zucker fa/fa and Fa/- rat are compared. The weights of liver and adipose tissues of the rats fed the MCT diet are little different from those of the two other groups, but they are always higher in obese rats than in lean rats. After feeding the MCT diet, the amounts of the constituent octanoic and decanoic acids in liver and adipose tissues are higher in the fa/fa rat than in the Fa/- rat. The rate of lipogenesis in liver and adipose tissues of the obese rat fed the MCT diet remains high.

Adipose Tissue↗

Prospective controlled study of androgen effects on red cell oxygen transport and work capacity in chronic hemodialysis patients.

Effects of androgens on red blood cell (RBC) oxygen transport, RBC metabolism and work capacity in chronic hemodialysis patients were evaluated in a prospective controlled study. Compared to control subjects, patients given nandrolone decanoate had a sustained fall in RBC ATP and a transient rise in RBC DPG but P50 values were unchanged. Despite increases in RBC mass of 16-44% on androgen therapy, exercise on the treadmill improved in only 1 patient and actually declined in 3 others. Thus, these preliminary observations suggest that androgens may not improve hemoglobin-oxygen transport and that androgen-induced increases in red cell mass may only balance increased tissue oxygen requirements produced by these anabolic hormones.

Anabolic Agents↗

Regeneration of murine megakaryocytopoiesis and the hematopoietic inductive microenvironment after sublethal whole body irradiation by treatment with an anabolic steroid.

The ability of the anabolic steroid nandrolone decanoate (ND) to increase megakaryocytopoiesis (MP) and the hematopoietic-inductive microenvironment (HIM) after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation (2 Gy) and on the next 2 days, mice were injected with 1.25 mg of ND in propylene glycol intraperitoneally. Irradiated control mice received only vehicle. Compared to controls, drug-treated mice showed a 151% increase in the platelet level on day 14. Drug-treated mice also demonstrated a significant rebound in MP, as colony-forming progenitor stem cells (CFU-Mk) from bone marrow rose to 288% of control by day 8 and from spleen to 599% by day 1 following the last drug injection. In addition, drug-treated mice produced a 286% increase in bone marrow and a 378% in splenic stromal cell colonies on day 5 following drug treatment. These results demonstrate that ND enhances MP and HIM following sublethal irradiation. After hematopoietic suppression, ND may serve to stimulate MP and HIM recovery both at the stem cell level and in peripheral blood.

Anabolic Agents↗

The possibility of lidocaine ion pair absorption through excised hairless mouse skin.

The purpose of the present research was to test the ion pair absorption hypothesis with respect to the topical route of drug delivery. The experiment consisted of preparing various lidocaine-n-alkanoate ion pairs, then characterizing them by proton magnetic resonance spectroscopy, elemental analysis and conductivity. Percutaneous absorption studies through excised hairless mouse skin were carried out using ethanolic solution of radiolabeled 14C-lidocaine-octanoate, 14C-lidocaine-decanoate and 14C-lidocaine-dodecanoate. Studies were conducted under steady-state conditions using Bronaugh's flow-through apparatus and normal saline as the receptor fluid. Ethanolic solution of a lidocaine base served as a control. The apparent differences in flux between lidocaine and the various ion pairs were statistically significant (p less than 0.05). The differences among the fluxes of the various ion pairs were not statistically significant (p greater than 0.05), nor were the differences in lag times (p greater than 0.05). The difference between the flux values of lidocaine-1-14C-dodecanoate and 14C-lidocaine-dodecanoate infers that lidocaine-dodecanoate did not cross the excised, full-thickness, hairless mouse skin as an intact 1:1 ion pair. The formation of weakly associated ion pairs was suggested by the apparent low-association constants (Ka = 15-17 liters/mol) obtained at 25 degrees C in methanol by conductometric analysis.

Animals↗

Effects of an anabolic steroid on plasma amino acids, proteins, and body composition in patients receiving intravenous hyperalimentation.

In this controlled trial we have studied the effect of anabolic steroid on ill surgical patients receiving intravenous hyperalimentation. Body composition, plasma proteins, and amino acids were compared in each of two groups of 12 patients before and after 14 days of intravenous feeding. The patients in one group were given 100 mg of nandrolone decanoate at the commencement of study and again one week later. Body weight, muscle (AMC), plasma transferrin, prealbumin, and retinol-binding protein were increased comparably in both groups. An apparent gain in total body nitrogen was not significant. However, anabolic steroid caused greater gain of water requiring a more liberal use of diuretics, but prevented the gains of fat, triglyceride and insulin that occurred in the control group. Most plasma amino acids increased due to intravenous hyperalimentation but decreased in patients given anabolic steroid. It is concluded that in patients who may be in the catabolic phase of recovery anabolic steroid probably enhances amino acid and water uptake by tissues and increases the utilization of fat but, does not promote any greater increase in "visceral" proteins than during intravenous hyperalimentation alone.

Aged↗

The effect of anabolic steroids and corticosteroids on healing of muscle contusion injury.

The effect of an anabolic steroid (nandrolone decanoate, 20 mg/kg) and a corticosteroid (methylprednisolone acetate, 25 mg/kg) on healing muscle injured with a drop-mass technique in a reproducible muscle contusion injury model in the rat was studied. Healing was determined by measuring active contractile tension in each muscle and histologic analysis. At day 2, the corticosteroid group showed significant improvement in both twitch and tetanic strength relative to the controls. At day 7, this effect was reversed and the corticosteroid muscles were significantly weaker than the control muscles, but there was still no significant effect seen in the anabolic steroid group. At day 14, the corticosteroid muscles were totally degenerated, with disorganized muscle fiber architecture. The anabolic steroid muscles were significantly stronger in twitch, and a similar trend was seen in tetanus relative to control muscles. The results indicate that in an animal model corticosteroids may be beneficial in the short term, but they cause irreversible damage to healing muscle in the long term, including disordered fiber structure and a marked diminution in force-generating capacity. Anabolic steroids may aid in the healing of muscle contusion injury to speed the recovery of force-generating capacity. Although anabolic steroids are considered renegade drugs, they may have an ethical clinical application to aid healing in severe muscle contusion injury, and their use in the treatment of muscle injuries warrants further research.

Anabolic Agents↗

Testosterone administration increases insulin-like growth factor-I levels in normal men.

Although testosterone (T) administration can increase insulin-like growth factor-I (IGF-I) when administered to hypogonadal men, no studies have examined whether this occurs in normal men. The present study was undertaken to determine if an increase in IGF-I may be part of the anabolic effect of androgens. We enrolled 11 normal men in a randomized, double-blinded cross-over study. Subjects were assigned to receive either T enanthate (TE) (300 mg im, each week) or nandrolone (ND) decanoate (300 mg im, each week) for 6 weeks. After a washout period subjects were administered the alternate treatment. Pre- and posttreatment serum was analyzed for IGF-I by RIA after acid-ethanol extraction. Results expressed as mean +/- SEM (Table 1). IGF-binding protein-3 was measured by RIA and was unchanged in the TE treatment and decreased significantly after ND treatment. Although GH levels were not significantly different after either TE or ND treatment, they tended to increase after TE treatment (1.23 +/- 0.28 ng/mL vs. 3.3 +/- 1.03 ng/mL) but remained unchanged after ND treatment (1.68 +/- 0.68 ng/mL vs. 1.89 +/- 0.64 ng/mL). Serum total T levels increased 32 +/- 0.05 nmol/L in the TE-treated men, but fell by 7 +/- 0.02 nmol/L in the ND-treated men (P < 0.0001). Serum estradiol levels rose by 193.04 +/- 19.82 pmol/L in the TE-treated men although falling by 50.65 +/- 34.50 pmol/L in the ND-treated men (P < 0.0002). These data indicate that when normal men are given TE, serum IGF-I levels increase after 6 weeks of treatment. Treatment with ND did not change serum levels of IGF-I but did decrease the level of the major serum IGF-BP and therefore the level of bioavailable IGF-I may be increased in the ND group.

Adult↗

Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men.

The effect of exogenous androgens on glucose metabolism is controversial. This study was designed to clarify the impact of testosterone enanthate (TE), an aromatizable androgen, and nandrolone decanoate (ND), a nonaromatizable androgen, on glucose disposal. Eleven healthy men were enrolled in a randomized, double-blind cross-over study. All subjects completed two treatment cycles consisting of two weekly injections of placebo followed by six weekly injections of either TE (300 mg/week) or ND (300 mg/week). Treatment periods were separated by a 4-week washout. A tolbutamide-modified, frequently sampled, iv glucose tolerance test was used to assess insulin-dependent and insulin-independent glucose disposal. Data were analyzed using Bergman's minimal model. Parameters examined included acute insulin response to glucose, fasting insulin level, glucose disappearance constant, insulin sensitivity index, glucose effectiveness at basal insulin (SG), and glucose effectiveness at zero insulin (GEZI). Neither androgen adversely affected glucose disposal. To the contrary, treatment with ND actually improved noninsulin-mediated glucose disposal as expressed by SG and GEZI. In ND-treated men, SG (x 10(-2) min(-1)) rose from 2.4 +/- 0.2 at the end of the placebo period to 3.7 +/- 0.6 after treatment (P < 0.05), whereas GEZI (x 10(-2) min(-1)) increased from 1.8 +/- 0.2 to 3.1 +/- 0.6 (P < 0.01). We conclude that the treatment of normal men with supraphysiological doses of either TE or ND does not adversely affect glucose metabolism. Treatment with a nonaromatizable androgen, such as ND, actually improves glucose metabolism by enhancing noninsulin-mediated glucose disposal.

Adult↗

Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women--a clinical research center study.

Abdominal fat distribution is influenced by androgen levels in both men and women. The purpose of this study was to assess the effects on fat distribution of administering nandrolone decanoate (ND; an anabolic steroid with weak androgenic activity) or spironolactone (SP; an antiandrogen) in obese postmenopausal women. The design was a randomized, placebo-controlled, 9-month trial with simultaneous calorie restriction for weight loss. Women in all three groups lost comparable amounts of weight, but the ND-treated women gained lean mass relative to the other two groups (P < 0.0005) and lost more body fat than women in the SP group (P < 0.01). The resting metabolic rate also increased slightly in the ND group. ND treatment produced a gain in visceral fat, as determined by computed tomography scan, and a relatively greater loss of sc abdominal fat. SP-treated women lost significantly less sc fat than the other two groups. Serum cholesterol decreased in the placebo group, but increased slightly in the other two groups (significant for SP vs. placebo, P < 0.05). High density lipoprotein cholesterol decreased significantly in the ND-treated women. There were no significant changes in fasting glucose or insulin sensitivity. We conclude that administration of exogenous androgens modulates body composition in obese postmenopausal women and independently affects visceral and sc abdominal fat.

Adipose Tissue↗

Differences in the induction of carboxylesterase RL4 in rat liver microsomes by various perfluorinated fatty acids, metabolically inert derivatives of fatty acids.

Differences in the ability of metabolically inert peroxisome proliferators [perfluoro-n-decanoic acid (PFDA, C10), perfluoro-n-octanoic acid (PFOA, C8), perflorooctane sulfonic acid (PFOS, C8) and 1H,1H-pentadecafluoro-n-octanol (PFOL, C8)] to induce liver microsomal carboxylesterase RL4 in male rats were studied by evaluating changes in the RL4 content by immunoblot analysis with a specific antibody. The administration of PFOA, PFOS and PFOL markedly increase the content of carboxylesterase RL4. On the other hand, PFDA decreases PNPA, BUTA, and ISOC hydrolase activity, and slightly increases the carboxylesterase RL4 content.

Alkanesulfonic Acids↗

Resin glycosides. XXV. Multifidins I and II, new jalapins, from the seed of Quamoclit x multifida.

Alkaline hydrolysis of the ether-soluble resin glycoside fraction of seeds of Quamoclit (Q.) x multifida, a hybrid between Q. pinnata and Q. coccinea, gave new glycosidic acids, multifidinic acids A and B, along with two known glycosidic acids, quamoclinic acid A and operculinic acid A, and three organic acids, (2S)-2-methylbutyric acid, n-decanoic acid and n-dodecanoic acid. Further, as major ether-soluble resin glycosides, new jalapins named multifidins I and II, were isolated accompanied by quamoclins I-IV, which were previously obtained from seeds of Q. pinnata. The structures of multifidins I and II, and multifidinic acids A and B have been determined on the basis of chemical and spectral data.

Butyrates↗

Chronic administration of anabolic androgenic steroid alters murine thyroid function.

PURPOSE: The administration of anabolic-androgenic steroids (AAS) to improve athletic performance has increased notably during the past three decades, even among nonathletes. Thyroid function is affected by AAS use in humans, although the mechanisms of the effects of AAS are unclear. We evaluated the effects on thyroid function of supraphysiologic doses of nandrolone decanoate (DECA), which is one of the most anabolic-androgenic steroids (AAS) used. METHODS: Male Wistar rats were treated with vehicle or 1 mg.100 g(-1) body weight (b.w.) of DECA, once a week for 8 wk, intramuscularly. We analyzed thyroperoxidase (TPO) activity, type 1 iodothyronine deiodinase (D1) activities in liver, kidney, pituitary, and thyroid, and serum levels of total T3, total T4, free T4, and TSH. Parametric and nonparametric t-tests were employed for statistical analyses. RESULTS: Treated animals showed a significant increase in the weight of kidneys and heart, and a decrease in the relative testis weight. Retroperitoneal adipose tissue was only slightly decreased. DECA treatment induced a significant increase in the absolute and relative thyroid gland weight. The concentrations of total serum T3, free T4, and TSH decreased significantly with treatment, but total serum T4 levels were unchanged. Thyroperoxidase activity was unaltered, whereas liver and kidney D1 activities were significantly increased, but pituitary and thyroid D1 did not change. CONCLUSION: Our data indicate that DECA exerts direct actions on the thyroid gland and in the peripheral metabolism of thyroid hormones and might lead to thyroid dysfunction.

Animals↗

A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial.

STUDY OBJECTIVES: Skeletal muscle weakness commonly occurs in patients with COPD. Long-term use of systemic glucocorticosteroids further contributes to muscle weakness. Anabolic steroids could be an additional mode of intervention to improve outcome of pulmonary rehabilitation by increasing physiologic functioning, possibly mediated by increasing erythropoietic function. PATIENTS AND METHODS: We randomly assigned 63 male patients with COPD to receive on days 1, 15, 29, and 43 a deep IM injection of 50 mg of nandrolone decanoate (ND) [Deca-Durabolin; N.V. Organon; Oss, The Netherlands] in 1 mL of arachis oil, or 1 mL of arachis oil alone (placebo) in a double-blind design. All patients participated in a standardized pulmonary rehabilitation program. Outcome measures were body composition by deuterium and bromide dilution, respiratory and peripheral muscle function, incremental exercise testing, and health status by the St. George's Respiratory Questionnaire. RESULTS: Treatment with ND relative to placebo resulted in higher increases in fat-free mass (FFM; mean, 1.7 kg [SD, 2.5] vs 0.3 kg [SD, 1.9]; p = 0.015) owing to a rise in intracellular mass (mean, 1.8 kg [SD, 3.1] vs - 0.5 kg [SD, 3.1]; p = 0.002). Muscle function, exercise capacity, and health status improved in both groups to the same extent. Only after ND were increases in erythropoietic parameters seen (erythropoietin: mean, 2.08 U/L [SD, 5.56], p = 0.067; hemoglobin: mean, 0.29 mmol/L [SD, 0.73], p = 0.055). In the total group, the changes in maximal inspiratory mouth pressure (PImax) and peak workload were positively correlated with the change in hemoglobin (r = 0.30, p = 0.032, and r = 0.34, p = 0.016, respectively), whereas the change in isokinetic leg work was correlated with the change in erythropoietin (r = 0.38, p = 0.013). In the patients receiving maintenance treatment with low-dose oral glucocorticosteroids (31 of 63 patients; mean, 7.5 mg/24 h [SD, 2.4]), greater improvements in PImax (mean, 6.0 cm H(2)O [SD, 8.82] vs - 2.18 cm H(2)O [SD, 11.08], p = 0.046), and peak workload (mean, 20.47 W [SD, 19.82] vs 4.80 W [SD, 7.74], p = 0.023) were seen after 8 weeks of treatment with ND vs placebo. CONCLUSIONS: In conclusion, a short-term course of ND had an overall positive effect relative to placebo on FFM without expanding extracellular water in patients with COPD. In the total group, the improvements in muscle function and exercise capacity were associated with improvements in erythropoietic parameters. The use of low-dose oral glucocorticosteroids as maintenance medication significantly impaired the response to pulmonary rehabilitation with respect to respiratory muscle function and exercise capacity, which could be restored by ND treatment.

Aged↗

Implications of basic pharmacology in the therapy with esters of nandrolone.

Experiments in rats have shown that esters of nandrolone injected intramuscularly, are absorbed from the depot according to the kinetics of a first-order reaction. The nature of the fatty acid chain in the ester determines the half-life of the compound in the depot. Once released from the depot, the ester is rapidly hydrolyzed by the esterases in the plasma. As a result, free nandrolone is the pharmacologically active agent whereas its availability to the target organs depends on the half-life time of the ester in the depot. It has been demonstrated that various androgenic target organs respond in a different manner to the changes in the concentration of nandrolone occurring during the period of resorption of the ester. This might explain the dissociation of anabolic from androgenic effects observed with esters of nandrolone. Knowing that the half-life for nandrolone decanoate in man is similar to that in rats, theoretical considerations are given with a number of dosing schemes.

Animals↗