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PubMed1997

Anabolic-androgenic steroid effects on sexual receptivity in ovariectomized rats.

Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long-Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long-Evans rats received estradiol benzoate (EB; 2.0 micrograms/day s.c.) for 6 consecutive days followed by 15 days of EB concurrent with daily s.c. injections of 7.5 mg/kg of one of the following AAS compounds: 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats.

Anabolic Agents↗
PubMed1979

Effects of glucocorticosteroids on cultured human skin fibroblasts. V. Influence of anabolic steroids on the inhibitory effects of clobetasol-17-propionate on cell proliferation and collagen synthesis.

As previously found, the glucocorticosteroid clobetasol-17-propionate inhibits cell proliferation during the early growth stage of normal baby foreskin fibroblasts and collagen synthesis in confluent cultures of these cells. The degree of inhibition of cell proliferation decreases with increasing cell density and, moreover, is transient. The anabolic steroids nandrolone and nandrolone-phenyl-propionate have similar effects on these cells. Likewise the magnitude of the inhibition is dose-dependent. When present together the two types of drug do not act in an additive manner. Even at low concentrations the anabolic steroids abolish the inhibitory effect of the glucocorticosteroid on cell proliferation. Furthermore, in this case only the inhibitory effect of the glucocorticosteroid on collagen synthesis is found and there is no further increase in this effect due to the presence of the anabolic steroids. Our results imply that the use of low concentrations of anabolic steroids combined with glucocorticosteroids in topical application to the skin may abolish some of the undesirable side effects of the glucocorticosteroids.

Betamethasone↗
PubMed1993

Behavioral effects of long-term administration of an anabolic steroid in intact and castrated male Wistar rats.

Once a week, intact and castrated male Wistar rats were intramuscularly injected with a 0.2 ml suspension of either 0, 10, or 50 mg nandrolone decanoate in cottonseed oil, for 8 consecutive weeks. After the sixth injection, locomotor activity was measured in an open-field and the acquisition of lever press behavior was assessed in an autoshaping procedure. Subsequently, all subjects were exposed to four sessions of continuous reinforcement prior to one session in which the effects of steroid administration on extinction were assessed. Locomotor activity decreased for all groups of rats with continued exposure to the open-field, differences between groups were not observed. Rats treated with the highest dose of nandrolone decanoate spent more time in the margin of the open-field. There were no significant differences between groups on any of the learning measures. Long-term, high-dose steroid administration in conjunction with mild food deprivation inhibited growth in intact and castrated rats, while low dose administration affected body weight in intact rats only. Steroid administration resulted in heavier and enlarged kidneys and lighter testes as well. These results suggest that the administration of anabolic steroids not only produces observable physiological changes, but that it may also affect spontaneous behavior. The failure to find differences in learning indices may have been a function of the particular paradigms used in the present experiment.

Anabolic Agents↗
PubMed2003

Effects of anabolic steroids and antioxidant vitamins on ethanol-induced tissue injury.

Various mechanisms are involved in the process of ethanol-induced tissue impairment. Oxidative stress and its effects are among the most important. We compared the effects of antioxidant vitamins (vitamin C and E in combination) and steroids (testosterone and nandrolone separately) on the toxicity of ethanol in rats. Animals (male Wistar rats, n = 48) were randomised into following groups-Control, Ethanol, Testosterone, Ethanol + Testosterone, Ethanol + Nandrolone, Ethanol + Vitamins. Alcohol was given daily by gavage in a dose of 5 g/kg of body weight. On the 27th day of the study the animals were sacrificed by decapitation and tissue samples were taken. Metabolic status, parameters of the hepatic metabolism, hormone levels (testosterone, ACTH, corticosterone), lipoperoxidation markers (malondialdehyde and conjugated diens in forebrain cortex and in cerebellum) and advanced glycation end-products were analysed. Tissue samples underwent histological examination. Histological outcomes showed a protective effect of antioxidants on hepatic and cerebellar injury caused by chronic ethanol intake. Anabolic steroids protected especially the central nervous tissue against the toxicity of alcohol. Both, antioxidant vitamins and anabolic steroids protect against the ethanol-induced toxicity, however, this effect is tissue specific.

Adrenocorticotropic Hormone↗
PubMed1999

Testing for anabolic steroids in hair from two bodybuilders.

Two male bodybuilders were recently arrested by the French customs in Strasbourg (France) in possession of 2050 tablets and 251 ampoules of various anabolic steroids. It was claimed that the steroids were for personal use and not for trafficing as suggested by the police. Urine and hair specimens were collected from both suspects to clarify the claims. Nandrolone, stanozolol, testosterone and their corresponding metabolites were identified in the urine of both subjects. After decontamination, the hair was hydrolyzed by sodium hydroxide in presence of deuterated internal standards. After extraction with ethyl acetate and silylation, the drugs were identified by GC-MS in the electron impact mode. Hair from both males were positive for nandrolone (196 and 260 pg/mg), testosterone (46 and 71 pg/mg) and stanozolol (135 and 156 pg/mg), clearly indicating steroids abuse. Although not yet recognized by the International Olympic Committee, hair analysis may be a useful adjunct to conventional drug testing in urine from athletes.

Anabolic Agents↗
PubMed2001

Detection and determination of anabolic steroids in nutritional supplements.

A method is described for the determination of anabolic steroids including testosterone, 19-nor-4-androstene-3,17-dione, 4-androstene-3,17-dione and nandrolone in food supplements. Initial clean-up is done by HPLC followed by determination with GC/MS. A 'contaminated' food supplement was analysed and appeared to contain 19-nor-4-androstene-3,17-dione and 4-androstene-3,17-dione. One capsule of this nutritional supplement was ingested by five male volunteers. Urine samples were collected and analysed by GC/MS and GC/MS-MS. Neither the ratio testosterone/epitestosterone, nor the ratio androstenedione/epitestosterone increased significantly. Concentrations above 2 ng/ml for norandrosterone, the major metabolite of nandrolone, were detected until 48-144 h after ingestion of the food supplement.

Anabolic Agents↗
PubMed2004

Norandrosterone and noretiocholanolone concentration before and after submaximal standardized exercise.

19-Norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are the two main urinary indicators used to detect illegal use of nandrolone. Recent studies showed that 19-NA and 19-NE can be endogenously produced in non-treated humans. The concentrations were close to the threshold of the International Olympic Committee (IOC), i.e. 2 ng/ml for men and seem to increase after prolonged intense effort. Androgens are involved in the biosynthesis of estrogens and estrogen has a protective effect against skeletal muscle damage following eccentric exercise. Furthermore, the testicular tissue can synthesize 19-norandrogens from androgens, we hypothetisize that the 19-norandrogen production might be influenced by muscle damage following eccentric exercise. Therefore the purpose of this study is to examine if three different exercise methods will influence the urinary concentration of 19-NA and 19-NE in healthy young subjects. Fifteen amateur hockey players undertook a 30 min submaximal standardized exercise protocol. They were randomised for three different types of exercise, namely a cycle ergometer test (cyclic muscle activity), a treadmill test (concentric muscle activity), or a bench-steptest (eccentric muscle activity) at a target heart rate corresponding to 65 % (+/- 5 %) of Karvonen heart rate. Urine samples were obtained before the test and 60 min and 120 min after the end of exercise. Subjects completed a Likert scale of muscle soreness before and 12 h after exercise. 19-NA and 19-NE were determined by gas chromatography-tandem mass spectrometry (GC-MS-MS). Baseline urinary 19-NA and 19-NE concentrations were under limit of detection of 0.05 ng/ml, except for one sample (0.13 ng/ml). No 19-NA or 19-NE could be detected post exercise. In our experimental conditions, the exercise mode (eccentric or concentric) had no impact on 19-NA or 19-NE excretion. Our findings confirm that the current International Olympic Committee threshold level for nandrolone metabolites is sufficiently high to avoid false positive cases.

Adult↗
PubMed1991

Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders.

The effects of anabolic steroids on body composition, blood pressure, lipid profile and liver functions were studied in male body builders who received a weekly i.m. injection of nandrolone-decanoate (100 mg) or placebo for 8 weeks in a double blind way. In addition, 5 body builders received the same dosage of nandrolone-decanoate or placebo, in a double blind cross-over design during two 8-week periods, interspersed by 12 weeks. Anabolic steroids induced a 25-27% decrease in HDL-cholesterol, which was virtually reversed 6 weeks after cessation of drug use. In the SAD group an increase in diastolic blood pressure was observed, which returned to pre-anabolic values approximately 6 weeks after cessation of drug administration. No deleterious effects of anabolic drugs on plasma activity of liver enzymes were found. Increases in lean body mass were found in all groups, though the increase in the subjects who received anabolic steroids was superior to that in the placebo-treated subjects. The increase in lean body mass suggests increases in muscle mass.

Adult↗
PubMed2000

Respective effects of anabolic/androgenic steroids and physical exercise on isometric contractile properties of regenerating skeletal muscles in the rat.

We examined the respective effects of anabolic-androgenic steroids and physical exercise on the contractile properties of regenerating fast and slow hindlimb skeletal muscles. Degeneration/regeneration of the left extensor digitorum longus muscles (EDL) and soleus of young Wistar male rats was induced by a snake venom (Notechis scutatus scutatus) injection. During muscle regeneration, experimental rats were either treated with nandrolone (NAN, nortestosterone, im, 2 mg X kg(-1) X week(-1), or endurance exercised on a treadmill (EXE, 60 min x day(-1), 10-40 m X min(-1). Twenty-one days after injury, isometric contractile properties of regenerating muscles were studied in situ. Neither the nandrolone treatment nor the physical exercise program was able to change significantly muscle contraction parameters both in twitch and tetanus in both regenerating EDL and soleus (p > 0.05). However, we observed a greater peak twitch tension in NAN versus grouped control and EXE EDL (p < 0.01). In conclusion, endurance exercise program or anabolic-androgenic steroid (nortestosterone) treatment did not significantly improve isometric contractile properties of regenerating slow and fast muscles in the male young rats.

Anabolic Agents↗
PubMed1986

A specific radioimmunoassay for the detection of 19-nortestosterone residues in urine and plasma of cattle.

19-Nortestosterone (Nandrolone) is illegally used as a growth promoter for meat producing animals. This work describes a radio-immunoassay (RIA) to detect, in cattle urine, Nandrolone and its metabolites. The antiserum was specific for 19-nortestosterone and its main metabolites, and to a lesser extent for Trenbolone (17 beta-hydroxyestra-4,9,11-trien-3-one). The sensitivity of this assay was 6 ug/l at 90 % B0/T binding. This assay can be used in forensic control of illegal treatment with 19-nortestosterone in meat production.

Animals↗
PubMed2003

Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells.

Involvement of intracellular Ca(2+) and ERK1/2 phosphorylation in the fast nongenomic effects of androgens in myotubes was investigated. Testosterone or nandrolone produced fast (<1 min) and transient increases in intracellular Ca(2+) with an oscillatory pattern. Calcium signals were slightly reduced in Ca(2+)-free medium, but lack of oscillations was evident. Signals were blocked by U-73122 and xestospongin B, inhibitors of inositol 1,4,5-trisphosphate (IP(3)) pathway. Furthermore, IP(3) increased transiently 2- to 3-fold 45 sec after hormone addition. Cyproterone neither affected the fast Ca(2+) signal nor the increase in IP(3). Calcium increases could also be induced by the impermeant testosterone conjugated to BSA, and the effect of testosterone was abolished in cells incubated with guanosine 5'-O-(2-thiodiphosphate) or pertussis toxin. Stimulation of myotubes with testosterone, nandrolone, or testosterone conjugated to BSA increased immunodetectable phosphorylation of ERK1/2 within 5 min, and this effect was not inhibited by cyproterone. Phosphorylation was blocked by the use of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethylester, U-73122, and xestospongin B as well as by dominant negative Ras, MAPK kinase (MEK), or the MEK inhibitor PD-98059. In addition, guanosine 5'-O-(2-thiodiphosphate) or pertussis toxin blocked ERK1/2 phosphorylation. These results are consistent with a fast effect of testosterone, involving a G protein-linked receptor at the plasma membrane, IP(3)-mediated Ca(2+) signal, and the Ras/MEK/ERK pathway in muscle cells.

Androgen Receptor Antagonists↗
PubMed1977

Virilizing activities of various steroids in female rat fetuses.

Virilizing activities of nineteen steroids were examined by a method measuring the abridgment of urovaginal septum length of female rat fetuses directly under microscope, following oral administration of the steroids to the mothers for 4 days during the late period of gestation. The characteristics of the virilizing activities of the steroids seemed to depend on their chemical structures. No virilizing activities were observed in progesterone, retroprogesterone, chlormadinone acetate and nandrolone phenpropionate. The introduction of 6-methyl and 17-acetoxy groups into progesterone exhibited a marked virilizing activity. With testosterone and its derivatives, the introduction of 17alpha-ethynyl group into testosterone slightly decreased the virilizing activity compared with the parent compound. On the contrary, the introduction of [3, 2-C] pyrazole ring in addition to the saturation of A-ring strikingly increased the virilizing activity. The most active virilizing steroid in this group was stanozolol followed by oxymetholone, methyl-testosterone and dimethysterone. Testosterone propionate was assumed to be less active than methyltestosterone by this route. With 19-nortestosterone derivatives, the virilizing activities of compounds with 17alpha-ethynyl group were moderate, but the presence of 17alpha-ethyl group caused a marked increase of virilizing activity. While, nandrolone phenpropionate with long side chain at C-17 exhibited no significant virilizing activity. The present results show the possibility of the evaluation on a potential virilizing activity of compounds in the female fetus, and also suggest that a dossociation between the virilizing activity and the androgenic activity may exist among some compounds.

Animals↗
PubMedDate not supplied

Proposed mechanisms for the anabolic steroid-induced increase in myocardial susceptibility to ischaemia/reperfusion injury.

UNLABELLED: Androgenic anabolic steroids (AAS) are often used by athletes to enhance athletic performance but are strongly associated with detrimental cardiovascular effects including sudden cardiac death. HYPOTHESIS: AAS use increases myocardial susceptibility to ischaemia/reperfusion injury. METHODS: Rats were trained (swimming) with or without intramuscular injection of nandrolone laurate (0.375 mg/kg). Untrained rats with or without nandrolone served as controls. Hearts were mounted on the Langendorff perfusion apparatus and mechanical function was measured before and after 20-min normothermic global ischaemia. Myocardial tissue samples were collected for determination of tissue cyclic nucleotide and TNFalpha concentrations. RESULTS: Anabolic steroids decreased the rate pressure product (RPP) of the exercise-trained rat heart [34 582 +/- 1 778 mmHg/min vs 28 868 +/- 2 446 mmHg/min for exercise-trained steroid-treated hearts (p < 0.05)]. Reperfusion RPP was lower in both the sedentary, and the exercise-trained, steroid-treated hearts than in their concurrent vehicle-treated controls (18 276 +/- 2 026 mmHg/min vs 12 018 +/- 1 725 mmHg/min for sedentary steroid-treated hearts and, 21 892 +/- 2 912 mmHg vs 12 838 +/- 1 536 mmHg/min for exercise-trained steroid-treated hearts). Myocardial TNFalpha [267.75 +/- 44.25 pg/g vs 190.00 +/- 15.75 pg/g (p < 0.05)] and cAMP concentrations [406.04 +/- 18.41 pmol/g vs 235.6 +/- 43.26 pmol/g (p < 0.05)] were elevated in the steroid-treated hearts when compared with their untreated counterparts. CONCLUSIONS: Supraphysiological doses of anabolic steroids, whether taken during exercise training or under sedentary conditions increase myocardial susceptibility to ischaemia/reperfusion injury in our model. This increased susceptibility may be related to steroid-induced increases in the pre-ischaemic myocardial cAMP concentrations and/or increases in both pre-ischaemic and reperfusion TNFalpha concentrations.

Anabolic Agents↗
PubMed2005

[Expression of androgen receptor on fibroblast and hepatocyte of rats after deep second-degree burn caused by scalding].

OBJECTIVE: To investigate the effect of protein anabolic hormone on fibroblast and hepatocyte of rat and the mechanism therein involved. METHODS: Thirty-two Wistar rats with deep second-degree scald injury of 20% total body surface area (TBSA) were randomly divided into two groups to receive either 5 mg/kg of an anabolic steroid--nandrolone phenylpropionate (NP group) or normal saline as placebo (control group) every other day. Mean Integrated Optical Density (mIOD) of androgen receptor (AR) in fibroblast and hepatocyte of rats were measured by immunohistochemistry individually on the post-burn days 4, 7, 14 and 21. RESULTS: The expression levels of AR on fibroblast and hepatocyte in NP group were significantly higher than those in the control group respectively. CONCLUSION: Nandrolone phenylpropionate can enhance the expression and activation of AR on fibroblast and hepatocyte.

Animals↗
PubMed1989

[Determination of some androgens and anabolic steroids in human urine by HPLC].

A simple method for determining androgens and anabolic steroids in human urine by HPLC has been developed. The compounds studied are nandrolone, methandienone, testosterone, methyltestosterone, testosterone propionate and nandrolone phenylpropionate. The stationary phase used is C8 bonded silica. Isocratic elution was done with CH3OH-CH3CN-H2O (4:5:6) and programmed flow. Detection limit can be less than 1 ng at the wavelength of 254 nm. The standard curves for each steroid have been set using internal standard (progesterone) and peak height ratio. Linear relationship exists between the ratio and concentration for each steroid. High and stable recovery has been achieved using Sep-Pak C18 cartridges for urine sample clean-up. The operation of the method is simple. The enzymatic hydrolyzation of conjugated steroids in human urine has also been investigated.

Anabolic Agents↗
PubMed1978

Effect of drugs on the stimulation threshold of the human heart.

Clinical measurements were made of the effects of various drugs on the stimulation threshold of human heart [right ventricle]. Of antiarrhythmic drugs, a marked and prolonged elevation of the stimulation threshold was produced by procainamide, quinidine, and aimaline. Relatively short-lasting elevation was elicited by local anaesthetics [trimecaine, lidocaine]. Beta-blockers were little effective. No detectable effect on the stimulation threshold was produced by phenytoin and digitalis glucosides from the group of antiarrhythmics. The deepest and most prolonged depression of the stimulation threshold was achieved with anabolics [nandrolone phenylpropionate, nandrolone decanoate] and with high doses of prednisone and of 6-methylprednisolone sodium succinate. Hydrocortisone was ineffective. A slight and brief depression was produced by atrophine. The effects of sympathomimetics were complicated: at stimulation with short pulses the threshold was always raised. At stimulation with long pulses the effects were variable, mostly biphasic [occasionally triphasic]: a transitory depression of the stimulation threshold was followed by a marked elevation. The I-t curve's slope altered. In exit block, sympathomimetics are indicated because of their chronotropic effect, not because of their questionable effect on the stimulation threshold. A number of drugs, often administered to stimulated patients, produced no effect on the stimulation threshold: antibiotics, nitrites, purine compounds, opiates, and others.

Adrenergic beta-Antagonists↗
PubMed2005

Detection, quantification and confirmation of anabolic steroids in equine plasma by liquid chromatography and tandem mass spectrometry.

Anabolic androgenic steroids are related to the male sex hormones and are abused in equine sports. In an effort to deter the abuse of anabolic steroids, a sensitive LC-MS/MS method was developed for detection, quantification and confirmation of eight major anabolic steroids (testosterone, normethandrolone, nandrolone, boldenone, methandrostenolone, tetrahydrogestrinone (THG), trenbolone, and stanozolol) in equine plasma. Formation of solvent adduct ions of the analytes was observed under electrospray ionization (ESI) conditions, and desolvation of the solvent adduct ions by source collision-induced decomposition (CID) increased the abundance of the [M+H]+ ions as well as the multiple-reaction monitoring (MRM) signals. ESI (+) and APCI (+) were compared with respect to sensitivity for the analytes and the former provided better sensitivity. The matrix effect on ion suppression or enhancement was evaluated, and was negligible. Confirmation of the analytes was performed using criteria of three ion transitions and LC retention time of each analyte. The limit of detection (LOD) and quantification (LOQ) was 25 pg/mL. The limit of confirmation (LOC) was 25 pg/mL for boldenone; 50 pg/mL for normethandrolone, nandrolone, and methandrostenolone; and 100 pg/mL for testosterone, THG, trenbolone, and stanozolol. The analytes were evaluated for stability and found to be stable in plasma for 24h at room temperature, 13 days at 4 degrees C, and 34 days at -20 and -70 degrees C. The method was successfully applied to analyses of equine plasma samples for pharmacokinetics study. This method is sensitive and useful for detection, quantification and confirmation of these anabolic steroids in equine plasma.

Anabolic Agents↗
PubMed2002

The effects of drug abuse on the stress responsive hypothalamic-pituitary-adrenal axis and the dopaminergic and endogenous opioid systems.

OBJECTIVE: Drugs of abuse have a significant impact on the stress responsive hypothalamic-pituitary-adrenal (HPA) axis and an abnormal response to stress may mediate the development or maintenance of addictive diseases. In animals, drugs of abuse, such as cocaine, lead to an activation of the HPA axis. Drugs of abuse also have an impact on the endogenous opioid system (EOS) and the dopaminergic system. Each of these systems has also been implicated in the mediation of aggressive behaviors. This brief report focuses on the effects of drugs of abuse on the stress responsive HPA, EOS and dopaminergic systems, and the role of these systems in mediating aggression and comorbidity of substance abuse and aggressive behaviors. METHOD: Rodents were administered either 'binge' pattern cocaine (15 mg/kg x 3 each day) or the androgenic anabolic steroid nandrolone decanoate and the effects on mRNA levels, receptor binding and circulating levels of stress hormones were analyzed. RESULTS: Both cocaine and nandrolone decanoate significantly impact the HPA axis, the EOS and the dopaminergic systems. CONCLUSION: Drugs of abuse impact substantially the same neural systems that affect aggressive behavior.

Dopamine↗