In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.     

Evidence for sex-dependent anabolic response to androgenic steroids mediated by muscle glucocorticoid receptors in the rat

The muscle anabolic/anti-catabolic activity of the androgenic steroids testosterone and trenbolone was studied in rats to investigate whether such steroids act as agonists via muscle androgen receptors, or as antagonists that oppose the catabolic effects of endogenous glucocorticoids via their interaction with muscle glucocorticoid receptors. For comparison, the effects of the potent glucocorticoid antagonist RU486 were also examined. The parameters measured included growth rate, muscle weight, serum growth hormone and corticosterone levels, and receptor binding parameters in muscle cytosol. Females responded better than males to anabolic treatment with the androgenic steroids. Ovariectomy or adrenalectomy abolished this response. Neither the sex difference nor the requirement for ovaries or adrenals could be explained in terms of muscle receptor parameters or serum growth hormone levels. The muscle anabolic activity of androgenic steroids was restored when castrated males were treated with oestradiol and when adrenalectomized females were treated with corticosterone. RU486 also prevented the catabolic/anti-anabolic activity of exogenous corticosterone in adrenalectomized rats. Testosterone and RU486 behaved as anti-glucocorticoids in vivo since they inhibited glucocorticoid-induced liver tyrosine aminotransferase activity. The results suggest that anabolic steroids can act via muscle glucocorticoid receptors, thereby antagonizing the catabolic activity of endogenous glucocorticoids, rather than via muscle androgen receptors.     

Analysis of anabolic steroids in hair: Time courses in guinea pigs

Sensitive, specific, and reproducible methods for the quantitative determination of eight anabolic steroids in guinea pig hair have been developed using LC/MS/MS and GC/MS/MS. Methyltestosterone, stanozolol, methandienone, nandrolone, trenbolone, boldenone, methenolone and DHEA were administered intraperitoneally in guinea pigs. After the first injection, black hair segments were collected on shaved areas of skin. The analysis of these segments revealed the distribution of anabolic steroids in the guinea pig hair. The major components in hair are the parent anabolic steroids. The time courses of the concentrations of the steroids in hair (except methenolone, which does not deposit in hair) demonstrated that the peak concentrations were reached on days 2-4, except stanozolol, which peaked on day 10 after administration. The concentrations in hair appeared to be related to the physicochemical properties of the drug compound and to the dosage. These studies on the distribution of drugs in the hair shaft and on the time course of their concentration changes provide information relevant to the optimal time and method of collecting hair samples. Such studies also provide basic data that will be useful in the application of hair analysis in the control of doping and in the interpretation of results.     

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)     

Cholesterol homeostasis in the guinea pig. The importance of quantitating net tissue accumulation of cholesterol in sterol balance studies

Sterol balance measurements of whole body cholesterol synthesis were performed in guinea pigs to determine the relative quantitative importance of dietary cholesterol intake, endogenous cholesterol synthesis, fecal steroid excretion and net tissue accumulation in cholesterol homeostasis of a rapidly growing animal. Sterol inputs were from diet (33%) and endogenous synthesis (67%); sterol outputs, as fecal neutral and acidic steroids, accounted for 60% of the total input, the remainder being used for the demands of tissue growth. The data demonstrate that the measurement of total body cholesterol synthesis can be grossly underestimated in this rapidly growing animal if net tissue accumulation of cholesterol is not considered in the balance measurement.     

Visual documentation of ovine pituitary gland development with magnetic resonance imaging following zeranol treatment

The objective of the current study was to determine whether magnetic resonance imaging (MRI) could be successfully utilized to document the effect of an oestrogenic anabolic agent on pituitary gland growth. The experimental animals consisted of two 1/2 sibling Suffolk wethers (castrated rams), which received either no implant (control, n = 1) or a 24 mg zeranol implant at day 0 and day 42 (zeranol; n = 1). Animals were anaesthetized with propofol and supported with oxygen during the MRI procedure. A mobile MRI unit with a 0.5 tesla (T), superconducting magnet was used to obtain 3 mm thick, non-contrast enhanced, T1-weighted (TR 500-600, TE25) sagittal, transverse and dorsal images of the pituitary gland. Sagittal images were recorded only when the mesencephalic aqueduct and infundibulum were distinctly visible in the same image. Pituitary glands were imaged at 14-day intervals for 70 days to determine if and when the anabolic effects of zeranol on pituitary gland growth could be visualized using MRI techniques. Three separate measurements of the pituitary gland dimensions made with the on-screen cursor were averaged to calculate pituitary gland dimensions and volume. A computer-assisted image analysis system and laser film images were used to determine pituitary gland area. Increases in pituitary gland volume for control and zeranol-treated animals were evident within 14 days, and by the end of the 70-day study, the increase in pituitary volume for the zeranol-treated animal was three times greater than that of the control animal. Overall, our results indicate that MRI technology can be successfully used to document the development of the pituitary gland in vivo. Application of knowledge gained from this novel approach to study the growth, development and function of endocrine glands over time, and within the same animal, will enhance human and animal endocrine diagnostic procedures.     

Further regression of seminal vesicles of castrated guinea pig by administration of cyproterone acetate

It has been established that a low level of secretory activity persisted in seminal vesicles of guinea pigs long after castration and that this may be due to a higher extratesticular androgen level in this animal. A RIA study revealed that the normal serum testosterone concentration of the guinea pigs was comparable to that of the rats, but the basal serum testosterone level after castration was ten times higher than rats under a similar condition. It was also shown that cyproterone acetate did not significantly lower the basal serum testosterone concentration in the castrated guinea pigs. The higher basal serum testosterone level is believed to be responsible for the slow and incomplete regression of this gland in the guinea pigs. There was a significant reduction in wet weight of the seminal vesicles after the treatment of castrated guinea pigs with cyproterone acetate. Ultrastructural study showed that there were both qualitative and quantitative changes in the cytoplasmic organelles. The Golgi apparatus further reduced in size and in the number of associated vesicles and vacuoles. There was a marked decrease in the number and size of secretory granules and lysosomes and an increase in the degree of undulation of the basement membrane. Accumulation of lipid droplets and glycogen was commonly observed. All these morphological evidences showed that further regression of the castrated guinea pig seminal vesicles can be achieved by cyproterone acetate treatment.     

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

The present study aimed to evaluate some cytochrome P450 metabolic enzyme activities in hepatic microsomes prepared from entire male pigs (uncastrated pigs), surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). The activities of the following enzymes were measured: ethoxyresorufin O-deethylase (EROD, CYP1A1/1A2), methoxyresorufin O-deethylase (MROD, CYP1A2), pentoxyresorufin O-depentylase (PROD, CYP2B), coumarin hydroxylase (COH, CYP2A) and p-nitrophenol hydroxylase (PNPH, CYP2A/2E1). The total cytochrome P450 contents were not affected by either surgical or immunocastration. Hepatic microsomal activities for EROD, PROD, COH and PNPH were lower in entire male pigs compared with surgically castrated and immunocastrated pigs (P < 0.05). Surgically and immunocastrated male pigs were similar with respect to EROD, MROD, PROD and COH activities (P > 0.05), whereas surgically castrated pigs exhibited lower PNPH activity compared with immunocastrated pigs (P = 0.029). The effect of different concentrations of testicular steroids - testosterone, 17β-estradiol, free estrone and androstenone - on enzyme activities was evaluated by in vitro microsomal study. Testosterone at the concentration of 8 pmol/ml inhibited EROD activities and estradiol-17β at the concentration of 1.8 pmol/ml inhibited PROD activities in hepatic microsomes from surgically castrated pigs. The highest concentration of androstenone (7520 pmol/ml) inhibited COH activities, whereas a 42-fold lower concentration of androstenone (180 pmol/ml) stimulated COH activities in surgically castrated pigs. Both free estrone (3.5 pmol/ml) and androstenone (55 pmol/ml) inhibited EROD activities in microsomes from entire male pigs. Stimulation of COH activities by the highest dose of free estrone (18 pmol/ml) was recorded in microsomes from entire male pigs. However, these effects of steroids were not concentration-dependent and the maximum extent did not exceed ±15% variation compared with the controls. There was no inhibition of PNPH activities in the hepatic microsomes from either entire or castrated pigs. In conclusion, we showed that EROD, PROD, COH and PNPH activities were lower in entire male pigs compared with those in surgically and immunocastrated pigs. Direct inhibition by the testicular steroids - testosterone, 17β-estradiol, free estrone and androstenone - was not the primary cause of the reduced enzyme activities.     

Administration of pregnenolone and dehydroepiandrosterone to guinea pigs and rats causes the accumulation of fatty acid esters of pregnenolone and dehydroepiandrosterone in plasma lipoproteins.

Steroids were administered continuously to guinea pigs and rats using subcutaneously applied silastic tubing implants, and the effects on circulating steroid and steroid conjugate levels were monitored. Using implants filled with pregnenolone, we observed that pregnenolone had a marked effect on increasing the levels of its fatty acid-esterified derivative, while dehydroepiandrosterone-releasing implants produced a rise in circulating nonconjugated dehydroepiandrosterone, androst-5-ene-3 beta,17 beta-diol, androstenedione, testosterone, and lipoidal derivatives of both dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol. Implants filled with androstenedione produced a 20-fold increase in plasma androstenedione levels relative to untreated controls and a corresponding five-fold increase over control testosterone levels. No fatty acid-esterified derivative of testosterone could be detected within the plasma. Lipoproteins were isolated from both rats and guinea pigs treated with implants filled with pregnenolone or dehydroepiandrosterone. The steroid and steroid fatty acid esters present in each fraction were analyzed, revealing that approximately 75% of all the fatty acid esters of pregnenolone recovered in the lipoproteins was localized within the high-density lipoprotein (HDL) fraction of both guinea pig and rat plasma. Similarly, lipoidal dehydroepiandrosterone was found associated predominantly with the low-density lipoprotein and HDL fractions in the guinea pig, while in the rat this steroid conjugate was exclusively within the HDL fraction. High-density lipoprotein-incorporated tritiated pregnenolone fatty acid esters and dehydroepiandrosterone fatty acid esters were injected into castrated male guinea pigs to study the fate of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of training and an anabolic steroid on murine red skeletal muscle. A stereological analysis.

The purpose of this study was the evaluation of changes induced by training (swimming 1 h/day, 5 days/week, 6 weeks) and an anabolic hormone (nandrolone decanoate, intramuscular injections of 15 mg.kg-1 per week) on fiber size, capillarization and mitochondrial fraction of murine soleus muscle. The animals (n = 32) were divided into 4 groups: a control group (C), that received the arachis oil carrier; a steroid group (S), that received the hormone; a training group (T), and a group that was submitted to training and to the administration of hormone (S + T). The soleus muscle was selected for quantitative light- and electron-microscopic evaluation. The muscle fiber size was increased in group T and decreased in groups S and S + T. The axial length of capillaries per unit volume of muscle decreased significantly in groups S and T. The number of capillaries per number of fibers showed a significant decrease in groups S and S + T and an increase in group T. The mitochondrial content decreased in group S, which suggested that anabolic steroids can be harmful for these organelles. This hypothesis was confirmed by histological evaluation at the electron-microscopic level. Many swollen and disrupted mitochondria were found in groups S and S + T. The results suggest that administration of nandrolone decanoate may have some deleterious effects on the muscle respiratory system (capillaries and mitochondria).     

Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens

Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5-reduction of the steroids does not occur in the muscle. 7-methyl-19-nortestosterone (MENT) does not get 5-reduced due to steric hindrance from the 7-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.     

Detection of anabolic steroid abuse using a yeast transactivation system

The classical analytical method for detection of anabolic steroid abuse is gas chromatography followed by mass spectrometry (GC/MS). However, even molecules with a chemical structure typical for this class of substances, are sometimes not identified in routine screening by GC/MS when their precise chemical structure is still unknown. A supplementary approach to identify anabolic steroid abuse could be a structure-independent identification of anabolic steroids based on their biological activity. To test the suitability of such a system, we have analyzed the yeast androgen receptor (AR) reporter gene system to identify anabolic steroids in human urine samples. Analysis of different anabolic steroids dissolved in buffer demonstrated that the yeast reporter gene system is able to detect a variety of different anabolic steroids and their metabolites with high specificity, including the so-called 'designer steroid' tetrahydrogestrinone. In contrast, other non-androgenic steroids, like glucocordicoids, progestins, mineralocordicoids and estrogens had a low potency to stimulate transactivation. To test whether the system would also allow the detection of androgens in urine, experiments with spiked urine samples were performed. The androgen reporter gene in yeast responds very sensitive to 5alpha-dihydrotestosterone (DHT), even at high urine concentrations. To examine whether the test system would also be able to detect anabolic steroids in the urine of anabolic steroid abusers, anonymous urine samples previously characterized by GCMS were analyzed with the reporter gene assay. Even when the concentration of the anabolic metabolites was comparatively low in some positive samples it was possible to identify the majority of positive samples by their biological activity. In conclusion, our results demonstrate that the yeast reporter gene system detects anabolic steroids and corresponding metabolites with high sensitivity even in urine of anabolic steroid abusing athletes. Therefore we believe that this system can be developed towards a powerful (pre) screening tool for the established doping tests. The system is easy to handle, robust, cost-efficient and needs no high-tech equipment. But most importantly, a biological test system does not require knowledge of the chemical structure of androgenic substances and therefore suitable to detect previously unidentified substances, especially those of the class of so-called designer steroids.     

Effects of training and methandrostenolone (an anabolic steroid) on energy metabolism in the guinea pig: changes in enzyme activities in gastrocnemius muscle and myocardium

Modifications of enzyme activities (creatine kinase and its B subunit; adenylate kinase; hexokinase; phosphofructokinase; lactate dehydrogenase; malate dehydrogenase, isocitrate dehydrogenase; citrate synthase; acetylcarnitine transferase; beta-hydroxyacetyl-CoA dehydrogenase; cytochrome c oxidase) in gastrocnemius muscle and myocardium were reported after two forms of training with or without administration of anabolic steroid. Endurance training was on a horizontal motor-driven treadmill, 2 km X hr-1, 5 days a week for 0.5 hr per day for 5 weeks. In the case of power endurance training there was a slope of 45 degrees. Enzyme activities in controls and treated guinea pigs, as well as treatment-induced enzyme activity changes are time dependent. Some of these activities correlate linearly with one another; such correlations characterize the effect of adaptation. Endurance training and power endurance training in this study induce similar modifications and seem to differ essentially in the daily work load. The anabolic steroid methandrostenolone (dianabol) induces modifications which training does not bring about but which training at least partially eliminates.     

The effect of ONO-3708, a novel TxA2 receptor antagonist, on U-46619-induced contraction of guinea pig and human tracheal strips in vitro and on bronchoconstriction in guinea pigs in vivo.

The effect of (9, 11), (11, 12)-didedoxa-9 alpha, 11-alpha-dimethylmethano-11,12-methano-13,14-dihydro-13-aza-14-oxo -15-cyclo-pentyl-16, 17, 18, 19, 20-pentanor-15-epi-TxA2 (ONO-3708) on 9,11-methanoepoxy-prostaglandin H2 (U-46619)-induced contraction of airway smooth muscle in the guinea pigs and human in vitro and bronchoconstriction in guinea pigs in vivo was investigated. In in vitro experiments, ONO-3708 inhibited the U-46619-induced contraction of isolated guinea pig and human tracheal smooth muscle in a dose related fashion (guinea pig; pA2=7.78, human; pA2 = 7.43). The contractions of guinea pig tracheal muscle caused by histamine and leukotriene D4 (LTD4) were not inhibited by ONO-3708. In in vivo experiments, intravenous injection of ONO-3708 at doses between 1 and 20 mg/kg inhibited the U-46619-induced increase of airway insufflation pressure as measured by Konzett-R?ssler method. In addition, ONO-3708 inhibited the U-46619-induced increase in airway reactivity to acetylcholine. These data suggest that ONO-3708 has possible therapeutic utility for asthma in which TxA2 participates.     

17α- and 17β-boldenone 17-glucuronides: Synthesis and complete characterization by H and C NMR

Boldenone is an androgenic anabolic steroid intensively used for growth promoting purposes in animals destined for meat production and as a performance enhancer in athletics. Therefore its use is officially banned either in animals intended for consumption or in humans. Because most anabolic steroids are completely metabolized and usually no parent steroid is excreted, metabolite identification is crucial to detect the illegal use of anabolic steroids either in humans or in livestock. 17α- and 17β-boldenone 17-glucuronides were synthesized, purified and characterized in order to provide suitable standards for the identification and quantification of these metabolites.     

Capillarity and oxygen diffusion distances of the soleus muscle of guinea pigs and rats. Effects of hyperthyroidism

The relationship between capillarity and oxidative capacity in the soleus muscle of rats and guinea pigs injected with triiodothyronine (T3) or with saline for up to 4 weeks was studied. The rats' soleus weight and FCSA were not affected by T3, but the guinea pigs that received T3 had smaller muscle weight and FCSA than the controls. The activities of cytochrome c oxidase and citrate synthase were significantly (41 and 65%) higher in the T3 than in the control rats. T3 administration did not affect the activities of these enzymes in the soleus of the guinea pigs. Capillary density (CD) was higher in T3 rats (892 +/- 80 vs 622 +/- 54 caps/mm2), and in T3 guinea pigs (1219 +/- 95 vs 739 +/- 142 caps/mm2). The higher CD in T3 rats was due to growth of new microvessels, while in the T3 guinea pigs it was due to a reduction in FCSA. Mean and maximal diffusion distances evaluated by the closest individual method were reduced by 2.02 and 3.37 microns in rats, and by 3.73 and 6.16 microns in guinea pigs. The magnitude of the reduction in diffusion distances brought about by the increased capillary density was partially offset by a concomitant change in the capillary arrangement from an ordered (hexagonal), towards a random distribution. These results seem to indicate that skeletal muscle capillarity is not necessarily determined by the oxidative capacity of the fibers.     

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)     

Binding of glucocorticoid antagonists to androgen and glucocorticoid hormone receptors in rat skeletal muscle

The binding of ten steroids possessing antiglucocorticoid activity has been studied in rat skeletal muscle cytosol. The affinity of these steroids for both the androgen and the glucocorticoid receptors was determined by competition with radioactive R1881 (methyltrienolone, metribolone) and dexamethasone, respectively. The antiglucocorticoid activity of these compounds was assessed in rat hepatoma (HTC) cells by measuring their inhibitory effect on the glucocorticoid-induced tyrosine aminotransferase activity. This led to identification of five novel in vitro glucocorticoid antagonists. All the steroids tested bound to both the glucocorticoid and the androgen receptors in muscle. Four steroids had an affinity for the glucocorticoid receptor higher than for the androgen receptor. The assumption is made that the steroids tested also behave as antagonists when binding to the glucocorticoid receptor in muscle and behave as agonists when binding to the androgen receptor. On this basis, the data allow one to compute a potential anticatabolic (PAG) and a potential anabolic (PAA) index for each compound. These indices might be of predictive value to determine whether these steroids exert their anabolic action in muscle through the glucocorticoid receptor or through the androgen receptor. The data also make it unlikely that satellite cells are a preferential target for anabolic steroids in muscle.     

Increased in vitro responses of tracheal smooth muscle from hyperresponsive guinea pigs

Repeated aerosol antigen challenge of previously sensitized guinea pigs induces airway hyperresponsiveness to inhaled acetylcholine. To determine the mechanism producing these airway changes and assuming that changes in the trachealis muscle reflect changes in muscle of the entire tracheobronchial tree, we examined the in vitro smooth muscle mechanics and morphometric parameters of tracheae from guinea pigs demonstrating hyperresponsiveness in vivo vs. tracheae from control guinea pigs. No differences between these groups were found in luminal volume at zero transmural pressure, passive pressure-volume characteristics, or area of airway wall. Smooth muscle areas were slightly less in tracheae from hyperresponsive guinea pigs. Tracheae from hyperresponsive guinea pigs had both significantly increased isovolumetric force generation and isobaric shortening compared with tracheae from controls when evaluated over the range of transmural pressures from -40 to 40 cmH2O. We conclude that the in vivo airway hyperresponsiveness induced with repeated antigen challenge is associated with both increased force generation and shortening of tracheal smooth muscle without increased muscle mass, suggesting enhanced contractile activity.