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Attenuated beta-adrenoceptor-mediated cardiac contractile responses following androgenic steroid administration to sedentary rats.

Androgenic steroids administered in doses at pharmacological levels to sedentary animals have been shown to result in a reduced beta-adrenoceptor-mediated increase in systolic cardiac performance when assessed in vivo. Whether the attenuated adrenergic response occurs as a consequence of alterations in either cardiac loads, heart rate, modifications in left ventricular (LV) geometry, or a decrease in myocardial contractile performance has not been determined. In this study the effect of chronic administration (over 3 months) of an androgenic steroid (nandrolone decanoate, 5 mg. kg(-1) biweekly) on the response of load-insensitive indices of myocardial contractile function [the slope of the LV systolic stress-strain relationship (LV-E(n)(max), where E(n)(max) is systolic myocardial elastance)] to an adrenergic-inotropic stimulus was examined ex vivo in paced rat hearts. Systolic cardiac performance was assessed at 300 beats. min(-1) in isolated constant flow perfused heart preparations both before and during 10(-8.5) mol. l(-1) isoproterenol (ISO) infusion (approximate concentration of ISO eliciting 50% maximal inotropic response to ISO). Steroid administration resulted in left-shifted LV systolic and diastolic pressure-volume (P-V ) relationships. The leftshifted P-V relationships were attributed, in part, to increased slopes of these relationships. However, the steroid-mediated increment in the slope of the systolic P-V relationship (systolic chamber elastance, E(max)) was not associated with a similar change in LV E(n)(max) [control 19.2 (SEM 2.1) g. cm(-2), steroid 18.3 (SEM 2.4) g. cm(-2)] as determined in the absence of ISO. Isoproterenol infusion resulted in an increase in both E(max) and E(n)(max) in the control rats, without altering systolic performance in the steroid treated rats. Consequently, in the presence of ISO, the steroid treated rats exhibited a similar E(max), but a reduction in E(n)(max) compared to the control rats [control 25.6 (SEM 1.9) g. cm(-2), steroid 18.5 (SEM 1.5) g. cm(-2); P < 0.05]. In conclusion, these results would suggest that chronic high dose androgenic steroid administration produces a decrease in myocardial contractile reserve to beta-adrenoceptor stimulation.

Anabolic Agents↗

Anabolic steroid treatment increases myofiber damage in mdx mouse muscular dystrophy.

In order to study whether myofiber size is an important determinant of the severity of dystrophic injury, mdx and control mice were treated with an anabolic steroid, nandrolone decanoate, for 3 weeks. Treatment resulted in a population of significantly smaller fibers in both strains, and was accompanied by an increase in the proportionate area or the number of foci of dystrophic injury in mdx soleus (slow-twitch) or tibialis anterior plus extensor digitorum longus (fast-twitch) muscles, respectively. As well, serum creatine kinase activity was increased in steroid-treated mdx mice. Fiber centronucleation, an index of accumulated injury and repair, in steroid-treated mdx soleus was doubled compared to that observed in soleus muscles from untreated mdx mice. There was no change in the distribution of immunoreactive basic fibroblast growth factor, important in muscle cell proliferation, with the increased damage from treatment. However, presumptive muscle precursor cells (identified by immunoperoxidase histochemistry for neural cell adhesion molecule), appeared to be more abundant in foci of very recent fiber damage in muscles from steroid-treated than untreated mdx mice. Results show that mdx dystrophy is worsened by anabolic steroid treatment, possibly by altered influences on muscle use patterns and muscle precursor fusion, and is not accompanied by an increase in fiber size.

Animals↗

Hormonal modulation of extinction responses induced by sexual steroid hormones in rats.

A functional interrelation between the nervous and endocrine systems has been established. However, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether sexual steroid hormones could modulate the extinction response of a passive avoidance conditioning in rats. Male Wistar rats, randomly assigned to five groups, two controls and three experimental groups, were submitted to a one-trial passive avoidance conditioning and tested for their retention 24 hr after and during 10 weeks. One control group received no treatment at all, the other received vegetable oil, and the three experimental received 20 mg of testosterone enanthate, 0.8 mg estradiol valerate, or 4 mg nandrolone decanoate, respectively. All substances were applied in a 0.3 ml volume, 24 hours before training and before testing for retention each week during 10 weeks. Results indicate that the extinction process is modulated by these hormones, since testosterone and estradiol facilitate extinction, whereas the anabolic androgen produced a resistance to the extinction process.

Anabolic Agents↗

Collagen synthesis in postmenopausal women during therapy with anabolic steroid or female sex hormones.

The effect of anabolic steroid therapy and estrogen-progestogen substitution therapy on serum concentration of procollagen type III aminoterminal peptide (PIIINP), a measure of collagen synthesis, in postmenopausal women was studied in two double-blind studies: (1) 39 women allocated to treatment with either 50 mg nandrolone decanoate as an intramuscular depot or placebo injections every third week for 1 year, and (2) 40 women allocated to receive either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate daily or placebo tablets for 1 year. Serum PIIINP was measured every 3 months during the study. Anabolic steroid therapy resulted in a more than 50% increase (P less than .001) in serum PIIINP at 3 months, which thereafter decayed but remained significantly increased throughout the study period. Serum PIIINP showed the same pattern during estrogen-progestogen therapy, but to a lesser degree. We conclude that anabolic steroids stimulate type III collagen synthesis in postmenopausal women, while estrogen-progestogen therapy may have such an effect, but only to a lesser degree.

Aged↗

Psychological and serum homovanillic acid changes in men administered androgenic steroids.

We report a difference in the response of serum homovanillic acid (HVA) and in the performance of some psychological tasks before and after the administration of testosterone enanthate (TE, 100 or 300 mg/wk) or nandrolone decanoate (ND, 100 or 300 mg/wk) for 6 wk to healthy men. Serum HVA was significantly increased in both the low- and high-dose ND groups, from 8.4 +/- 1.0 and 8.7 +/- 0.5 pmol/ml (mean +/- SE) to 11.6 +/- 1.7 and 10.7 +/- 1.1 pmol/ml respectively. No significant changes in HVA were observed for the groups administered TE, nor in 5-HIAA for any of the groups. The influence of ND on the dopaminergic system, which is reflected in increased serum HVA, appears to be independent from the psychological effects which were produced by both androgens. The only change in psychomotor test performance was an improvement in the first trial of a pegboard task. All subjects except those receiving ND (100 mg/wk) were significantly more optimistic in the prediction of their own performance for all nondominant hand tasks (pegboard and finger tapping). The "hostility" and "resentment and aggression" subscales of the MMPI increased significantly in all groups, more so in the high-dose groups.

Adult↗

Modulation of overload-induced inflammation by aging and anabolic steroid administration.

Aging can alter the skeletal muscle growth response induced by overload. The initiation of overload induces muscle extracellular matrix expansion, increased cellularity, and inflammatory gene expression, which are all related to processes important for myofiber growth. These remodeling processes are also biological targets of testosterone. It is not certain how aging affects the inflammatory response to functional overload and whether anabolic steroid administration can alter this response. The effect of anabolic steroid administration on inflammatory processes during functional overload is not known. The purpose of this study was to determine if age altered the skeletal muscle inflammatory response at the onset of functional overload and whether anabolic steroid administration would modulate this response in young or older animals. Five-month and 25 month F344 x BRN rats were given nandrolone decanoate (ND) (6 mg/kg bw/wk) or sham injections for 3 weeks, and then the soleus muscle was overloaded (OV) for 3 days by synergist ablation. ND alone induced a 230% increase in ED1(+) cells in 5 month muscle. Three days of OV had no effect on ED1(+) cell number at either age. OV combined with ND induced a 90% increase in ED2(+) cells in 5 month muscle, while there was no effect of either treatment alone at this age. In 25 month muscle, OV induced a 40% increase in ED2(+) cells. Regardless of age, OV induced muscle TNF-alpha mRNA expression (300%) and IL-6 mRNA expression (900%). ND attenuated OV-induced IL-6 mRNA but not TNF-alpha expression in both age groups. The overload induction of IL-1beta mRNA was 3-fold greater in 25 month muscle (1400%), compared to 5 month muscle (400%). ND administration ablated the overload IL-1beta mRNA induction in 25 month muscle. Anabolic steroid administration can suppress inflammatory cytokine gene expression at the onset of overload and this effect is age dependent.

Aging↗

Dihydrotestosterone and estrogen regulation of rat brain androgen-receptor immunoreactivity.

Androgen-receptor upregulation that occurs with androgenic-anabolic steroid (AAS) administration may be mediated by AAS metabolites, dihydrotestosterone (DHT), and estrogen. Castrated and intact male rats received 14 s.c. daily injections of AAS (2 mg/kg testosterone cypionate, 2 mg/kg nandrolone decanoate, and 1 mg/kg boldenone undecylenate in sesame oil vehicle), DHT (5 mg/kg dihydrotestosterone), EB (5 mg/kg estradiol benzoate), or sesame oil vehicle. Approximately 18-24 h after the fourteenth injection, brain tissues were removed and processed immunocytochemically using the PG-21 androgen-receptor antibody. As reported before, castration eliminated AR-ir (androgen-receptor immunoreactivity) and AAS upregulated AR-ir in the ventromedial hypothalamus (VMHVL), medial amygdala (MePV), and medial preoptic area (MPOM). When compared to AAS, DHT fully upregulated AR-ir in the VM VL and MPOM and partially upregulated AR-ir in the MePV. EB treatment partially upregulated AR-ir in the VMHVL and MePV, but not in the MPOM of castrated rats. Because AR-ir in the MPOM was consistently upregulated by DHT or AAS, and not EB, androgen-receptor availability in this region may be mediated specifically via androgen receptors.

Amygdala↗

Comparison of erythropoietic response to androgen in young and old senescence accelerated mice.

In this study, to clarify whether the functional capacity of hemopoietic progenitor cells and the micro-environment of aged mice are identical with those of the young, we investigated the changes in the number of hemopoietic progenitor cells and the production of regulatory cytokines from splenic cells as well as changes in the serum levels of cytokine in senescence-accelerated mice (SAM) after administration of 19-nandrolone decanoate (19-ND), a synthetic androgenic anabolic steroid. 19-ND induced an increase in erythroid colony-forming units (CFU-E), erythroid burst-forming units (BFU-E), and granulocytic-macrophage committed progenitor cells (CFU-GM) in bone marrow and spleen; especially remarkable increases were observed in the splenic CFU-E in both young and old mice. Antigen expression analysis of hemopoietic organs revealed that total TER-119+ cells per spleen of young and old mice with androgen treatment rose 2.6- and 3.2-fold over their respective control values. The responsiveness of hemopoietic progenitor cells to androgen did not change with age. Injection of 19-ND into young and old mice markedly enhanced the erythropoietin levels but not IL3 and GM-CSF levels in the serum of both groups. Cytokine production assessed by pokeweed mitogen-stimulated spleen condition medium showed an age-related decline. Androgen treatment could not influence IL-3 and GM-CSF production of spleen. These findings suggest that the spleen of both old and young mice served as the major site of regenerative repopulation of hemopoietic progenitors, especially the late erythroid progenitors in 19-ND-treated mice. The proliferative reserve of erythropoiesis with androgen treatment in aged mice was not reduced more than that in treated-young mice.

Aging↗

Anabolic-androgenic steroids affect the content of substance P and substance P(1-7) in the rat brain.

The effects of intramuscular (i.m.) injections of nandrolone decanoate (15 mg/kg/day), an anabolic-androgenic steroid, on the levels of substance P (SP) and on its N-terminal fragment SP(1-7) were examined in the male rat brain by radioimmunoassay. The results demonstrated that the SP immunoreactivity in amygdala, hypothalamus, striatum, and periaqueductal gray was significantly enhanced, whereas the concentration of the N-terminal fragment SP(1-7) was enhanced in the nucleus accumbens and in periaqueductal gray. In the striatum the steroid induced a decrease in the content of SP(1-7). The relevance of these peptides in connection with anabolic-androgenic steroid-induced aggression is discussed.

Anabolic Agents↗

Effects of anabolic steroids and endurance exercise on cardiac performance.

This study examined the effects of anabolic steroids and exhaustive endurance exercise, and the combination of both treatments on in vitro cardiac contractile function. Fifty-two male Sprague-Dawley rats were randomly assigned, in groups of 13, to one of the four groups: sedentary control (C), steroid-treated (ST), exercise-trained (E), and exercise plus steroid treated (E+S). Nandrolone decanoate was administered to the steroid-treated groups every 7-9 days during the 10 weeks study, while the C and E groups received glycerol injection on these occasions. The exercised rats ran on a treadmill wearing a collar weight (2-3% of body weight) for 50 min, 5 days a week. In vitro ventricular performance was assessed in isolated Langendorff perfused hearts in response to increasing left ventricular balloon volumes. Left ventricular +dP/dt, dP/dt at 60 mmHg developed pressure, tension time index, and Emax (slope of the pressure-volume curves) were significantly (p < 0.05) lowered in the E+S group, as compared to the C, E, or ST group. Meanwhile, the E group exhibited a higher (p < 0.05) left ventricular systolic pressure (LVSP) than the C and E+S groups. No significant differences in dP/dt/P, heart weight (wt), and heart wt to body wt ratio were detected among the four groups. Rats subjected to endurance exercise or anabolic steroid treatment alone exhibited no change in LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Anabolic Agents↗

NMR spectroscopy study of heart phospholipids. An exercise and anabolic steroids effect.

Because 31P NMR spectral analysis of phospholipid (PL) is an accurate and rapid technique for resolving the quantity of PL resonances and involving minimum chemical manipulations that may affect the integrity of the tissue (24-26), we studied the effect of anabolic steroid injection, exercise training, or a combination of both treatments on whole heart phospholipids using 31P NMR spectral analysis. Male Sprague-Dawley rats were randomly assigned to 4 groups of 11 each: sedentary control (C), steroid-treated (ST), exercise-trained (E), and exercise plus steroid-treated (ES). The ST and ES rats were administered nandrolone decanoate by i.m. injection every 7-9 d during the 10 wk study, while the C and E rats were injected with glycerol. The exercise rats ran on a treadmill, wearing a collar weight for 50 min/day, 5 days/wk. There was a significant difference in body wt among the four groups at the conclusion of the study; however, no significant differences in heart wt or in the ratio of heart wt:body wt were observed among the four groups. Myocardial phospholipid profiles of the exercise-trained rats were significantly (p less than 0.05) different from those of the untrained rats. The changes were enhanced somewhat by the steroid treatment. The profiles differed in the relative amounts of four of the nine myocardial phospholipids detected: phosphatidylcholine, phosphatidylethanolamine (PE), PE plasmalogen, and phosphatidylserine. We conclude that the observed changes in whole heart phospholipid compositions are due to experimental treatment specifically from exhaustive exercise and not from anabolic steroids or cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Food habits and appetite of elderly women at the time of a femoral neck fracture and after nutritional and anabolic support.

OBJECTIVE: To study appetite and food choices in lean elderly women at the time of a femoral neck fracture and after 6 months of nutritional and anabolic intervention. SUBJECTS AND METHODS: Forty-five nondemented women >70 years of age (mean +/- SD: 83 +/- 5 years) with a recent hip fracture and body mass index <24 kg/m2 (mean: 20.5 +/- 2.3) were interviewed about their appetite and dietary habits prior to fracture. The patients were randomized to treatment with a protein-rich liquid supplement (PR; 200 kcal and 20 g protein day(-1)) alone or in combination with nandrolone decanoate injections (PR/N) 25 mg i.m. every third week or to a control group (C). A second interview was conducted 6 months later. RESULTS: Reduced appetite before the fracture was reported by 60%. Half of the patients did not have dessert with any of their daily meals, one-third used low-fat margarines and one-third drank water with their meals. The estimated mean daily energy intake was 6.4 +/- 1.2 MJ (1541 +/- 304 kcal) indicating that three of four subjects did not meet their energy needs. At 6 months, 40% reported reduced appetite. There was no difference in the change of appetite between the three randomized groups. Still, half of the subjects appeared to not meet their energy needs. Protein intake increased in the PR and PR/N groups, in contrast to the controls (P = 0.002). CONCLUSION: Reduced appetite and insufficient energy intake was recorded in lean elderly women with a femoral neck fracture. Nutritional supplementation alone or in combination with an anabolic steroid increased protein intake without adversely affecting appetite.

Aged↗

Lipemic and lipoproteinemic effects of natural and synthetic androgens in humans.

Testosterone cypionate administration in weight-trained subjects reduced serum high-density lipoprotein cholesterol (HDL-C) levels without affecting the total cholesterol (Total-C)/HDL-C ratio. Nandrolone decanoate administration also reduced HDL-C levels, but elevated the Total-C/HDL-C ratio. These findings could not be attributed to changes in exercise patterns, dietary intake, or alcohol consumption. It is concluded that the synthetic androgen employed in this study produced a worsening of potential lipid-related risk factors for ischemic heart disease and that exogenous testosterone has a much less pronounced effect on such risk factors.

Adult↗

The effect of an anabolic steroid on body composition in patients receiving intravenous nutrition.

In this controlled trial we investigated the effect of an anabolic steroid, in terms of the changes in body composition that occurred in ill surgical patients requiring intravenous nutrition. Glucose was the sole non-protein energy source. The study was conducted over a 14-day study period in two comparable groups of 13 patients. The changes in body weight, fat, protein and water were measured. The control group received a nutrient solution of hypertonic dextrose and amino acids (44.8 +/- 8.2 kcal/kg/day), and the comparative group received the same solution (44.3 +/- 5.2 kcal/kg/day) and 100 mg of an intramuscular injection of nandrolone decanoate at the commencement of the study and again one week later. Over the two-week study period both groups gained body weight. In the controls this was composed of fat (0.4 kg) and water 1.5 kg). In the anabolic steroid group, weight gain was mainly water, and fat gain did not occur. Neither group gained body protein. Diuretic therapy was required more often (21 patient days compared with 5 patients days; p less than 0.001) in the anabolic steroid group to control excessive water retention. Our study has shown no benefit from an anabolic steroid when given in combination with a 14-day course of intravenous nutrition. Water retention was more of a problem with this therapy.

Aged↗

Muscle ultrastructure after strength training with placebo or anabolic steroid.

The influence of strength training on muscle fiber area, capillary ultrastructure, and capillary supply was studied in experienced male bodybuilders taking either anabolic steroids or a placebo. During 8 weeks, 13 subjects received a weekly injection of either placebo or nandrolone decanoate (starting dose 200 mg, followed by 100 mg weekly), in a double-blind, counterbalanced design. Before and after 8 weeks a needle biopsy was taken from the vastus lateralis muscle for studying morphometric characteristics of fibers and ultrastructure and morphometric characteristics of capillaries. The fiber cross-sectional area increased significantly only after steroid treatment. Capillary ultrastructure and capillary supply were not changed after the training period. In none of the measured parameters was any difference found between placebo and steroid treatment.

Adult↗

Anabolic steroids increase exercise tolerance.

The influence of an anabolic androgenic steroid (AAS) on thymidine and amino acid uptake in rat hindlimb skeletal muscles during 14 days after a single exhaustive bout of weight lifting was determined. Adult male rats were divided randomly into Control or Steroid groups. Nandrolone decanoate was administered to the Steroid group 1 wk before the exercise bout. [3H]thymidine and [14C]leucine labeling were used to determine the serial changes in cellular mitotic activity, amino acid uptake, and myosin synthesis. Serum creatine kinase (CK) activity, used as a measure of muscle damage, increased 30 and 60 min after exercise in both groups. The total amount of weight lifted was higher, whereas CK levels were lower in Steroid than in Control rats. [3H]thymidine uptake peaked 2 days after exercise in both groups and was 90% higher in Control than in Steroid rats, reflecting a higher level of muscle damage. [14C]leucine uptake was approximately 80% higher at rest and recovered 33% faster postexercise in Steroid than in Control rats. In a separate group of rats, the in situ isometric mechanical properties of the plantaris muscle were determined. The only significant difference was a higher fatigue resistance in the Steroid compared with the Control group. Combined, these results indicate that AAS treatment 1) ameliorates CK efflux and the uptake of [3H]thymidine and enhances the rate of protein synthesis during recovery after a bout of weight lifting, all being consistent with there being less muscle damage, and 2) enhances in vivo work capacity and the in situ fatigue resistance of a primary plantarflexor muscle.

Anabolic Agents↗

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension.

The efficacy of anabolic steroid treatment [0.3 or 0.9 mg nandrolone decanoate (Deca-Durabolin) per day] was examined in the context of sparing rodent fast-twitch plantaris and slow-twitch soleus muscle weight, sparing subcellular protein, and altering isomyosin expression in response to hindlimb suspension. Female rats were assigned to four groups (7 rats/group for 6 wk): 1) normal control (NC), 2) normal steroid (NS), 3) normal suspension (N-SUS), and 4) suspension steroid (SUS-S). Compared with control values for the plantaris and soleus muscles, suspension induced 1) smaller body and muscle weight (P less than 0.05), 2) losses in myofibril content (mg/muscle, P less than 0.05), and 3) shifts in the relative expression (expressed as %of total isomyosin) of isomyosins which favored lesser slow myosin and greater fast myosin isotypes (P less than 0.05). Steroid treatment of suspended animals (SUS-S vs. N-SUS) partially spared body and muscle weight (P less than 0.05) and spared plantaris but not soleus myofibril content (mg/muscle, P less than 0.05). However, steroid treatment did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs. NC), steroid treatment enhanced body and plantaris muscle weight but not soleus weight (P less than 0.05) and did not alter isomyosin expression in either muscle type. Collectively these data suggest that in young female rats anabolic steroids 1) enhance the body weight and the weight of a fast-twitch ankle extensor in normal rats, 2) ameliorate the loss in body weight, fast-twitch muscle weight and protein content and slow-twitch muscle weight associated with hindlimb suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

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↗