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Effects of submaximal training and anabolic androgenic steroids administration on steroidogenic enzyme activity in rat Leydig cells.

The purpose of the present study was to investigate the single and combined effects of submaximal training and anabolic androgenic steroids (AAS) treatment on the activity of 3beta hydroxysteroid dehydrogenase (3betaHSD) in rat Leydig cells (LC). Forty male Wistar rats were distributed into 4 groups. Half of them exercised on treadmill. After 2 weeks half of the trained and sedentary rats received weekly either 10 mg x kg(-1) Nandrolone Decanoate (ND) or Placebo (Pl) i.m. for 6 weeks. The day after the last exercises all the groups: 1) sedentary + Pl (SP); 2) sedentary + ND (SND); 3) trained + Pl (TP) and 4) trained + ND (TND) were decapitated. On fresh cryostat sections of the testes of each animal enzymehistochemical reaction for the activity of 3betaHSD was carried out. Our results demonstrate that in sedentary rats ND treatment decreased the activity of 3betaHSD in the LC in comparison to SP. Endurance training also decreased the activity of 3betaHSD in TP group compared to SP. On sections of the testes of group TND a pronounced reduction in the enzyme activities of 3betaHSD in the LC was found in comparison with the other groups. In conclusion we suggest that submaximal endurance training and/or administration of AAS downregulate the steroidogenic enzyme activity of rat Leydig cells.

3-Hydroxysteroid Dehydrogenases↗

A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases.

One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.

Anemia, Aplastic↗

Responsive estrogen-induced aplastic anemia in a dog.

A 4-year-old Airedale Terrier that had developed estrogen-induced aplastic anemia had a complete recovery after supportive treatment and weekly administrations of nandrolone decanoate. The anemia was induced iatrogenically by administration of estradiol cypionate (2 mg, IM each time) at 48- to 72-hour intervals. Clinical signs included lethargy, anorexia, and weakness; hemoglobin was 6.8 g/dl, PCV was 21%, and WBC was 1,500/dl. Supportive treatment included blood transfusions and administration of antibiotics, corticosteroids, and vitamins. Hematologic values returned to normal by day 81, and the dog has remained healthy for one year after treatment.

Anabolic Agents↗

Fertility of young mares after long-term anabolic steroid treatment.

The effect of prior treatment with anabolic steroids was studied in 46 three-year-old mares. In the preceding year, these mares had been assigned to 1 of 4 treatment groups and had received the manufacturer's recommended dosage of 1.1 mg of boldenone undecylenate (BU)/kg of body weight, 4.4 mg of boldenone undecylenate (4 BU)/kg, 1.1 mg of nandrolone decanoate (ND)/kg, or 0.04 ml of sesame oil/kg (control, C). Mares had received an injection every 3 weeks for 54 weeks for a total of 19 injections, with the final injection in December. In the following breeding season, fewer (P less than 0.05) mares in all groups previously administered anabolic steroids displayed estrous behavior than did mares in the control group. Duration of estrus was shortened (P less than 0.05) in mares that had received steroids. Abnormal sexual behavior that was observed during steroid treatment continued (P less than 0.05) for up to 6 months after treatment ceased. However, observations of abnormal behavior declined with time (P less than 0.05). All mares in each treatment group ovulated by the end of the trial, and the interval to first ovulation was similar (P greater than 0.05). Ovarian size, follicular development, and conditions of the tubular genitalia was adversely (P less than 0.05) affected in mares in all steroid-treatment groups until approximately the middle of March. After that time, no difference was noted among groups. First-cycle pregnancy rates were 83%, 67%, 50%, and 42% for mares in the untreated, BU, 4 BU, and ND groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of androgen on transient endogenous spleen colonies and other hemopoietic stem cells in mice.

To clarify the effects of androgen on hemopoiesis in mice, we investigated changes in hemopoietic stem cells at various stages of differentiation after injection of 19-nandrolone decanoate (19-ND). 19-ND induced (a) a marked increase in the population of CFUe, especially in the spleen, and (b) a less significant increase in the number of CFUs, GM-CFC, and BFUe. The number of endogenous spleen colonies developed transiently on day 4 after irradiation (TE-CFU) increased significantly, and the initiation and induction of erythropoietic maturation was enhanced. Growth of the pluripotent stem cells (CFUs) assessed by endogenous spleen colony formation was influenced more than was the population size. Production of erythropoietin (Ep) in mice was not affected by the treatment with 19-ND. These results indicate that 19-ND affects mature precursors in erythroid cell lineage rather than pluripotent stem cells and that the effect is unlikely to be induced through an increase in the production of Ep.

Animals↗

[Effect of anabolic steroid on immune response].

Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin.

Female↗

Reversal of cyclophosphamide induced neutropenia by hypertransfusion and androgen therapy.

We injected 300 mg/kg Cyclophosphamide i.p. into female AKR mice and rendered them reversably neutropenic. Group A was hypertransfused; Group B received 5 mg Nandrolone decanoate i.m. q.d X 2; and Group C received both. Group D served as a control. White blood cell counts were followed every other day for 10 days. The nadirs seen on all groups appeared on day 5. At day 10 counts in Groups A, B, and D had returned to normal, while the pattern of granulocyte decline and recovery in Group C was significantly faster than that seen in other groups, returning to normal at day 8. Hypertransfusion and androgen administration together significantly ameliorated drug-induced leukopenia, suggesting synergism. Thus manipulation of the stem-cell compartment may be clinically feasible.

Agranulocytosis↗

An acute myocardial infarction occurring in an anabolic steroid user.

Anabolic-androgenic steroid abuse is prevalent and has been associated with numerous adverse effects. The case being presented is of an amateur weight trainer, who suffered an acute myocardial infarction; his only significant risk factor was his nonmedical use of an anabolic steroid, nandrolone decanoate. This case presentation discusses the hematologic effects of this class of drugs and the subsequent impact on ischemic heart disease.

Adult↗

Clinical trials update in human immunodeficiency virus wasting.

The major acquired immunodeficiency syndrome (AIDS) clinical trials groups in the Division of AIDS of the National Institutes of Health have been investigating weight loss and wasting in persons with the human immunodeficiency virus (HIV) and AIDS. Both the AIDS Clinical Trials Group (ACTG) and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) have developed research projects to study the pathogenesis, diagnosis, prevention, and treatment of HIV-related malnutrition and wasting. This article reviews multicenter trials concerning HIV-related malnutrition and wasting conducted by the AIDS clinical trials groups. CPCRA trials will examine the effects of caloric supplements and triglycerides, or the use of megestrol acetate, oxandrolone, and progressive resistance training, on weight loss in patients with HIV-associated wasting. Planned ACTG trials will study the effects of the combination of megestrol acetate and testosterone, the testosterone derivative nandrolone decanoate, or highly active antiretroviral therapy on weight loss. Results from these studies may also have relevance to clinical oncologists who are treating patients with cancer-related cachexia.

Anabolic Agents↗

Androgens, estrogens, and the ultimate height in XO gonadal dysgenesis.

We observed 40 patients with 45,X gonadal dysgenesis from the age of 13 to 15 years until the age of 18 to 21 years. The ultimate height of the 12 nontreated patients was 143.2 cm. Of 15 patients treated with nandrolone phenpropionate or methandrostenolone, the ultimate height was 143.3 cm, and of 13 patients treated with ethinyl estradiol, the height reached was 144.1 cm. The mean height of ten patients first seen at the age of 25 to 31 years was 140.1 cm. The mean height at any age was almost identical in all the groups. The growth velocity was somewhat accelerated by anabolic steroids and to a lesser extent, by estrogens only during the first year of therapy, and this did not influence the ultimate height. We saw no deleterious effects of the estrogens. In all the groups, there were patients who grew for some time at rates of up to 4 to 6 cm/yr. Therefore, long-term follow-up studies are needed for the evaluation of the effects of any treatment.

Adolescent↗

Determination of four anabolic steroid metabolites by gas chromatography/mass spectrometry with negative ion chemical ionization and tandem mass spectrometry.

A gas chromatography/mass spectrometry method is described which uses negative ion chemical ionization and tandem mass spectrometry for the determination of anabolic steroid metabolites. Four anabolic steroid metabolites to be derivatized by Pentafluoropropionic anhydride (PFPA) were determined using gas chromatography/mass spectrometry (GC/MS) with negative chemical ionization (NCI) and NCI/MS/MS. The repeatability and reproducibility of this procedure were in the range of 5.3-9.7% and 6.1-10.2%, respectively. This method of derivatization with PFPA for NCI and NCI/MS/MS was useful to determine four metabolites of nandrolone, dromostanolone, methenolone and boldenone. The derivatized metabolites of boldenone could be detected to 2 ppb and the other three steroids could be detected to 25 ppb in urine at a signal-to-noise ratio of S/N = 3.

Anabolic Agents↗

Rapid test by liquid chromatography/tandem mass spectrometry to evaluate equine urine reactivity towards 17beta-OH steroids.

Bacteria frequently found in equine urine samples may cause degradation of 17beta-OH steroids. A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to evaluate the microbiological contamination of equine urine as a marker of poor storage conditions. Norethandrolone was used as the internal standard, and the linearity, sensitivity, precision and accuracy of the method were evaluated. 17beta-OH oxidation was demonstrated for testosterone, nandrolone, trenbolone and boldenone, but did not occur in alpha-epimers such as alpha-boldenone and epitestosterone, demonstrating the stereoselectivity of the reaction. A rapid test was performed by spiking one of the four 17beta-OH steroids in samples of diluted equine urine. The steroids were transformed into their respective ketones in the presence of bacterial activity. The test allows direct injection of diluted samples into the LC/MS system, without the need for prior extraction. Results show that the best method of storage is freezing at -18 degrees C. Urine specimens should be analyzed as soon as possible after thawing. This allows bacterial degradation of equine urine to be arrested temporarily, so that the urine can be used for qualitative or quantitative analysis of 17beta-OH steroids.

Animals↗

Aggression in male rats receiving anabolic androgenic steroids: effects of social and environmental provocation.

This study examined the effects of anabolic androgenic steroids (AAS) on aggression under different social and environmental conditions. Three AAS were tested in gonadally intact male rats: testosterone propionate (TP), nandrolone (ND), and stanozolol (ST). Doses of 5 mg/kg were given 5 times/week, with gonadally intact controls receiving vehicle only (propylene glycol). Animals received six weekly tests under each condition in a counterbalanced order. Results show that the three AAS differed in their ability to elicit aggression. Males receiving TP were more aggressive than controls, ND males were similar to controls, and ST males were less aggressive than controls. In the social and environmental provocation tests TP-treated males were more aggressive than other groups, but were able to discriminate between intact and castrated opponents and between their home cage and a neutral cage. In the environmental provocation test, TP males were also more aggressive against opponents when tested in the opponent's home cage. It is suggested that chronic exposure to high levels of TP does not eliminate the ability to discriminate between social or environmental cues, as might be expected if it induces a " 'roid rage." However, TP does increase the likelihood that the animal will respond with aggression/dominance in a provoking situation. All three AAS variably affected serum testosterone and LH levels, as well as testes, seminal vesicle, and prostate weights. No effect on body weight was observed.

Aggression↗

Physical provocation potentiates aggression in male rats receiving anabolic androgenic steroids.

Anabolic androgenic steroids (AAS) have been linked to indiscriminant and unprovoked aggression and violence. We employed a brief tail pinch to examine the effects of different AAS on intermale aggression in gonadally intact male rats in response to a mild physical provocation. Animals received 5 mg/kg testosterone propionate (TP), nandrolone (ND), or stanozolol (ST) 5 days/week. Controls received vehicle injections. After 12 weeks, rats were tested for aggression while treatments continued. Animals were paired with either gonadally intact or castrated opponents and were tested in the subject rat's home cage, the opponents's home cage, and a neutral cage. Aggression was tested during tail pinch of the subject rat and during tail pinch of the opponent rat. In TP-treated males, tail pinch significantly enhanced aggression in all social and environmental conditions compared to intact controls. TP treatment also significantly enhanced aggression when the opponents were tail pinched. Tail pinch did not increase aggression in ND-treated males, and aggression was significantly lower than controls in ST-treated males. As expected, cell nuclear androgen receptor binding was significantly elevated by the high dose of TP. Our results show that while AAS alone does not induce the indiscriminate and unprovoked aggression characteristic of 'roid rage, TP heightens the animals sensitivity to

Aggression↗

Effects of an anabolic hormone on striated muscle growth and performance.

Chronic administration of an anabolic hormone, nandrolone phenylpropionate, in sedentary female rats for 6 weeks gave a 20% increase in body weight and the same proportional increase in all muscles sampled (heart, diaphragm, soleus, TA, EHP and EDL), such that the muscle/body weight ratio was unchanged. Cardiac muscle was unresponsive to treatment. Acute stimulation of EDL via lateral popliteal nerve gave similar values for contraction time, 1/2 relaxation time and twitch:tetanus ratio in both groups suggesting no slowing of the muscle. Fatigue resistance of EDL was improved with 0.29 +/- 0.029 vs. 0.46 +/- 0.071 of maximum isometric twitch tension being developed after 10 min repetitive stimulation at 4 Hz. This improved endurance was not accompanied by any increase in strength and could not be explained on the basis of cellular hypertrophy, but appears to reflect an increased aerobic capacity of skeletal muscle. The proportion of FOG fibres in EDL increased, 38 +/- 1.1% vs. 46 +/- 1.1%, and this was paralleled in the other skeletal muscles. Specific hypertrophy of FOG and FG fibres could be conclusively demonstrated in soleus and TA, respectively.

Adenosine Triphosphatases↗

Effects of an anabolic hormone on aerobic capacity of rat striated muscle.

The effect of chronic administration for 6 weeks of an anabolic steroid, nandrolone phenylpropionate (Durabolin), was studied in three predominantly glycolytic muscles, and three oxidative muscles of sedentary female rats. Mean blood pressure and resting heart rate (HR) were lower in the anabolic-treated group, while the increase in HR during stimulation of EDL was reduced. No change was noted in the aerobic capacity of ventricular myocardium, although there was an increase in skeletal muscles due to a combination of increased capillary supply and/or TCA cycle enzyme activity. Capillary:fibre ratio (C:F) increased around 10% in glycolytic muscle with little effect on resting blood flow (BF). In EDL C:F was 1.1 +/- 0.02 vs. 1.2 +/- 0.01 and BF was 7.0 +/- 1.45 vs. 6.2 +/- 1.82 ml min-1 100 g-1 for control and Durabolin treated animals, respectively (means +/- SEM, n = 7). No increase in citrate synthase (CS) activity was evident. In soleus, where C:F was not significantly different between groups, CS activity increased from 3.9 +/- 0.34 to 5.9 +/- 0.40 microM g-1 min-1 (means +/- SEM, n = 7). Glycolytic capacity, indicated by pyruvate kinase activity, increased only in diaphragm. These data demonstrate that total oxidative metabolism of striated muscle does not necessarily increase with greater proportion of FOG fibres, nor is it always correlated with capillary supply. The positive myotrophic effect of Durabolin represents the sum of modest changes at different levels of organisation.

Aerobiosis↗

Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy.

Female Sprague-Dawley rats (n = 72), 6 months old, underwent either sham operation, oophorectomy, adrenalectomy, or combined oophorectomy and adrenalectomy (O&A). They were all maintained on normal saline ad libitum and 20 g/day 1.1% calcium chow. Nine weeks after operation, the trabecular bone volume of the distal femoral shaft was significantly lower (P less than 0.001) in the adrenalectomized (11.1%), oophorectomized (7.0%), and O&A (8.3%) animals than in sham-operated animals (19.8%). Eighteen weeks after operation, the trabecular bone volume in O&A animals had fallen to a mean of 3.8% (sham 17.0%), and the length of the femur had increased to 38.8 mm after O&A (sham 36.8 mm, P less than 0.01). O&A animals treated with 0.35 mg/kg/week nandrolone decanoate from 9 weeks postoperatively onward, had twice the femoral trabecular bone volume of untreated animals at 18 weeks (P less than 0.05). By contrast, no significant differences were found in vertebral body trabecular bone between any groups, including groups receiving treatment with androgens. We have found that, by 9 weeks after operation, adrenalectomy alone causes significant loss of metaphyseal trabecular bone, similar to the progressive loss seen after oophorectomy.

Adrenal Glands↗

The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine.

Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. [16,16(-2)H2]Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicular minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize [2H5]testosterone to [2H4]estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Allantois↗