Anabolic steroid usage in athletics: facts, fiction, and public relations

Anecdotal evidence suggests the widespread usage of anabolic steroids among athletes (20-90%), particularly at the professional and elite amateur levels. In contrast, scientific studies indicate that usage is rare and no higher than 6%. Conclusions from scientific studies suggest that anabolic steroid usage declines progressively from high school to college and beyond; however, anecdotal evidence claims the opposite trend. In this clash between "hard" scientific data vs. "soft" anecdotal information, it is natural that professionals would gravitate toward scientifically based conclusions. However, in the case of anabolic steroids (a stigmatized and illegal substance), should word-of-mouth testimony from individuals closest to the issues--those who have participated in and coached sports, those who have served as drug-testing overseers, and journalists who relentlessly track leads and verify sources--be set aside as irrelevant? Not if a complete picture is to emerge. In this review, hard scientific evidence is placed on the table side-by-side with soft anecdotal evidence, without weighting or bias. The purpose is to allow the opportunity for each to illuminate the other and, in so doing, potentially bring us a step closer to determining the true extent of anabolic steroid usage in athletics.     

New 4-methylated and 19-oxygenated steroids from the Formosan soft coral Nephthea erecta

Two new 4-methylated steroids, erectasteroids A and B (1 and 2), six new 19-oxygenated steroids, erectasteroids C-H (3-8) and two known 19-oxygenated steroids (9 and 10) were isolated from the acetone solubles of the Formosan soft coral Nephthea erecta. The structures were elucidated by extensive NMR spectroscopic analysis and their cytotoxicity against selected cancer cells was measured in vitro.     

New 19-oxygenated and 4-methylated steroids from the Formosan soft coral Nephthea chabroli

Chemical investigation of the Formosan soft coral Nephthea chabroli resulted in the isolation of four new 19-oxygenated steroids, nebrosteroids I-L (1-4), together with a new 4α-methylated steroid, nebrosteroid M (5). The molecular structures of these isolated metabolites were elucidated on the basis of extensive spectroscopic analysis and by comparison of the data with those of related metabolites. Compounds 1-5 were evaluated for anti-inflammatory activity using RAW 264.7 macrophages.     

Protective effect of corticosteroids on radiation pneumonitis in mice

We explored the protective effect of corticosteroids on the mortality of mice that received thoracic irradiation. Methylprednisolone, 100 mg/kg/week, given from 11 weeks after gamma irradiation of the thorax resulted in an increase in the LD50 (11-26 weeks) from 14.3 +/- 0.3 (mean +/- SE) Gy to 17.6 +/- 0.4 Gy, P less than 0.001, a protection factor of 1.2. Withdrawal of steroids at various times during the period of radiation pneumonitis resulted in accelerated mortality in the next 2-4 weeks, so that the cumulative mortality "caught up" with that of control animals by 4 weeks after steroid withdrawal. However, after the end of the usual period of pneumonitis withdrawal of steroids did not result in accelerated mortality, suggesting that the time when steroids are protective corresponds to the duration of pneumonitis. A smaller dose of steroids, 25 mg/kg/week, was found to be as protective as the larger dose used in the above experiments. The possibility that corticosteroids reduce mortality, even when given many weeks after radiation, may have important practical and theoretical implications.     

Characterization of the major steroids present in amniotic fluid obtained between the 15th and 17th weeks of gestation

In pooled amniotic fluid obtained between the 15th and 17th weeks of gestation the concentration of free steroids and steroid glucuronides was found to be 40 micrograms/dl. The concentration of steroid monosulfates and disulfates was 19 micrograms/dl. About half of the characterized steroids are progesterone metabolites. The "fetal type" 3 beta-hydroxy-5-ene steroids were found exclusively in the sulfoconjugated form. Their concentration represents 20% of the total steroid content. The identification of two 15 beta-hydroxylated C21 steroids, 3 beta,15 beta,17 alpha-tridoxy-5-pregnen-20-one and 5-pregnene-3 beta,15 beta,17 alpha,20 alpha-tetrol isolated from mid-pregnancy amniotic fluid is reported here. Metabolites of cortisol and 17-deoxycorticosteroid metabolites had similar quantitative importance, 8.6 and 9.4%, respectively.     

Fungi as a source of marker compounds for the control of illicit use of drugs: mesterolone as a case study

Introduction

Anabolic steroids are frequently misused for performance enhancement during sports competitions. One of the major bottlenecks in the confident analysis of steroids and their metabolites is the non-availability/cost of standard reference compounds.

Objective

The study objective was to identify the common metabolites of prohibited anabolic steroids that are produced in both fungi and human and thus can be synthesized in bulk using fungal cultures. Mesterolone is used as a case study.

Methods

The study was conducted in three steps; we first studied the fungal transformation of mesterolone. In the second step, these metabolites were used as references to detect in human urine after the oral use of mesterolone using LC-ESI-QqQ-MS/MS. In the third step, 12 fungal cultures were screened to evaluate their potential to produce reference markers.

Results

This led to the detection of two metabolites, 6α-hydroxymesterolone (M1) and 7α-hydroxymesterolone (M2) that were found to be common in both, fungal cultures and human urine samples. Moreover, Rhizopus stolonifer and Beauveria bassiana can be considered as good candidates to produce M1 and M2 metabolites, respectively.

Conclusion

This approach can be employed for the synthesis of marker compounds of other prohibited anabolic steroids thus can be detected efficiently during national and international sports competitions.

     

Synthesis of 19-nor-aldosterone, 18-hydroxy-19-nor-corticosterone and 18,19-dihydroxycorticosterone in the human aldosterone-producing adenoma

The recently synthesized 18-C-steroid derivative, 19-nor-aldosterone(19-nor- aldo) and 18-hydroxy-19-nor-corticosterone(18-OH-19-nor-corticosterone) possess mineralocoroticoid and hypertensinogenic activity. They and an additional newly synthesized steriod, 18,19-dihydroxycorticosterone[18,19(OH)2-corticosterone], may play a role in the etiology and pathogenesis of disorders thought to be caused by steroids with mineralocorticoid and hypertensionogenic properties. In this study we provide evidence that 19-nor-aldo, 18-OH-19-nor-corticosterone and 18,19(OH)2-corticosterone are produced in vitro by aldosterone-producing adrenal adenomas and adenomas and adenoma of Cushing's syndrome. "silent" adrenal adenomas and the adjacent adrenal tissue. Measurable amounts of these steroids were found in the incubation fluids of adrenal tissues using specific RIAs performed after a sequence of HPLC systems. The rates of production of the three steroids were high in the aldosterone-producing adrenal adenomas and in adrenal hyperplasia compared with in either Cushing's adenoma or "silent" adenoma.     

Effects of chronic ethanol ingestion on steroid profiles in the rat testis

Testosterone, seven of its potential precursors, three of its metabolites and estradiol were analyzed in testes from rats given ethanol for 23 days in a nutritionally adequate liquid diet. The results were compared to those obtained with pair-fed control rats. The concentrations of pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione and testosterone were markedly lowered in four of the five rats given ethanol. The concentrations of the other 3 beta-hydroxy-delta 5 steroids and estradiol were unchanged, resulting in significantly increased ratios between 17-hydroxypregnenolone and 17-hydroxyprogesterone (P less than 0.025) and between androstenediol and testosterone (P less than 0.025) in the ethanol-treated rats. The results indicate that chronic ethanol administration reduces formation of testosterone by affecting a step prior to pregnenolone. There may also be an effect on the conversion of some 3 beta-hydroxy-delta 5 to the corresponding 3-oxo-delta 4 steroids. The levels of testosterone and three other steroids in testes of rats given the liquid diet were significantly lower than those in testes of animals fed a standard rat chow. This indicates a dietary influence on testicular steroid concentrations.     

Polyhydroxylated sterols from the Indonesian soft coral Sinularia sp. and their effect on farnesoid X-activated receptor

Chemical investigation of the Indonesian soft coral Sinularia sp. resulted in the isolation of three known (1, 2 and 7) and five new (3-6 and 8) sterols, characterized by either 24-methylcholestane or gorgostane skeletons. The stereostructures of the new compounds have been elucidated by application of HR-MS and 2D NMR techniques. The isolated steroids have been evaluated for their interaction with the farnesoid X-activated receptor (FXR) and some of them, including the new compound 3 and gorgosterol (7), showed a consistent antagonistic activity, potentially useful for the treatment of cholestasis. The FXR antagonistic activity of gorgosterol (7) was also supported by gene expression experiments. Our results represent the first evaluation of soft coral steroids for interaction with nuclear receptors and qualify gorgosterol (7) as a new chemotype of FXR antagonist.     

New anti-inflammatory 4-methylated steroids from the Formosan soft coral Nephthea chabroli

Eight new 4-methylated steroids, nebrosteroids A-H (1-8) were isolated from the acetone solubles of the Formosan soft coral Nephthea chabroli. The structures were elucidated by extensive NMR spectroscopic analysis and their anti-inflammatory activity was measured in vitro.     

Effects of Anabolic Steroids on Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomised Controlled Trials

Background

Anabolic steroids are known to improve body composition and muscle strength in healthy people. However, whether anabolic steroids improve the physical condition and function in patients with chronic obstructive pulmonary disease (COPD) remains undetermined. A meta-analysis was conducted to review the current evidence regarding the effects of anabolic steroids on COPD patients.

Methods

A comprehensive literature search of PubMed and EMBASE was performed to identify randomised controlled trials that examine the effects of anabolic steroids on COPD patients. Weighted mean differences (WMDs) with 95% confidence intervals were calculated to determine differences between anabolic steroid administration and control conditions.

Results

Eight eligible studies involving 273 COPD patients were identified in this meta-analysis. Significant improvements were found in body weight (0.956 kg), fat-free mass (1.606 kg), St. George''s Respiratory Questionnaire total score (−6.336) and symptom score (−12.148). The apparent improvements in maximal inspiratory pressure (2.740 cmH₂O) and maximal expiratory pressure (12.679 cmH₂O) were not significant. The effects on handgrip strength, forced expiratory volume in one second (FEV₁), predicted FEV₁ percent, PaO₂, PaCO₂ and six-min walk distance were negative, with WMDs of −0.245 kg, −0.096 L/sec, −1.996% of predicted, −1.648 cmHg, −0.039 cmHg and −16.102 meters, respectively.

Conclusions

Limited evidence available from the published literature suggests that the benefit of anabolic steroids on COPD patients cannot be denied. However, further studies are needed to identify the specific benefits and adverse effects of anabolic steroids on COPD patients and to determine the optimal populations and regimes of anabolic steroids in COPD patients.     

神经活性甾体对神经元的作用

神经活性甾体是指神经组织中具有活性的甾体激素,根据甾体激素的作用机制可分为三类：（1）通过细胞表面离子通道型受体介导产生效应,这些受体包括GABAA受体,NMDA受体等。（2）通过G蛋白偶联的膜受体指导第二信使反应,再通过DNA结合蛋白,调节基因表达产生效应,（3）通过细胞内受体介导调控基因的表达产生效应,甾体激素的这些效应尤其是对离子通道型受体和G蛋白偶联型受体的调节作用,已引起重视。     

Dietary beta-sitosterol as an internal standard to correct for cholesterol losses in sterol balance studies

In the course of carrying out sterol balance studies in 19 patients, we gathered the following evidence that, in some but not all patients, considerable amounts of neutral sterols are "lost" during their passage through the intestinal tract. (a) Since plant sterols are largely nonabsorbable in man, they should be totally recovered in the feces; yet in many patients significantly less plant sterol than expected was recovered, the loss amounting to as much as 56% of daily intake. (b) In two patients in whom cholesterol-(14)C and beta-sitosterol-(3)H were instilled into the terminal ileum, from which neither sterol is absorbed, the feces contained 25% less of each isotope than was instilled. (c) In four patients fed radioactive cholesterol daily until the isotopic steady state was closely approximated, 28-50% of the isotope could not be accounted for. On the other hand, in five patients fed radioactive bile acids until the isotopic steady state was approximated, input equalled output as predicted. Since the amount of -sitosterol absorbed in man is limited (5% or less), this sterol can be used as an internal standard for upward correction of the figure obtained for the amount of neutral steroids excreted. The use of beta-sitosterol for this purpose is based on three considerations: (a) it passes through the intestine in the same physicochemical state as cholesterol; (b) it accompanies cholesterol at every step of its isolation and chromatographic measurement; and (c) it is lost to the same extent as cholesterol. Excretion data for fecal neutral steroids can therefore be corrected for irregular fecal flow as well as for the "unexpected loss" referred to. This loss seems to be due not to errors in stool collection or to technical errors, but to intestinal bacterial degradation of neutral 3beta-OH,Delta(5)-sterols to products not recognized as steroids in the analytical methods used.     

Structural specificity of steroids in stimulating DNA synthesis and protooncogene expression in primary rat hepatocyte cultures

Among the chemical compounds of varied structure which possess liver tumour-promoting are steroids, such as estrogens, pregnenolone derivatives and anabolic steroids. Although the mechanism(s) of tumour promotion in liver by these xenobiotics is not well understood, it is clear that growth stimulation is one important element in their action. As a basis for better defining whether steroids stimulate growth by a common mechanism or fall into sub-groups with differing actions, the effects of 46 steroids on DNA synthesis and the expression of protooncogenes c-fos and c-myc were examined in primary cultures of normal rat hepatocytes. Tentative groupings of steroids have been identified based on apparent structural requirements for stimulation of DNA synthesis, and effects of auxiliary factors in modulating this growth stimulus. For a "progestin" group, insulin appeared to be permissive for stimulation of DNA synthesis, and presence of an ester or hydroxyl group at 17alpha-position in combination with a non-polar group at C(6) appeared to be required for stimulation. For the pregnenes, dexamethasone was stimulatory. Structural requirements include a non-polar substitution at 16alpha-position and presence of a 6alpha-methyl group. Androgens were weak or ineffective stimulators of DNA synthesis. Anabolic steroids were weak to strong stimulators and alteration to A ring structure in combination with non-polar substitution at 17alpha-position appeared to be required for the activity. With the exception of the anabolic steroid, dianabol, there do not appear to be strong correlation between ability to stimulate DNA synthesis and ability to induce protooncogene expression among the steroids. This study provides a starting point for future more detailed examination of growth-stimulatory mechanism(s) of action of steroids in the liver.     

Shifts in preferred learning strategy across the estrous cycle in female rats

The current status of the effects of ovarian steroids on learning and memory remains somewhat unclear, despite a large undertaking to evaluate these effects. What is emerging from this literature is that estrogen, and perhaps progesterone, influences learning and memory, but does so in a task-dependent manner. Previously, we have shown that ovariectomized rats given acute treatments of estrogen acquire allocentric or "place" tasks more easily than do rats deprived of estrogen, but acquire egocentric or "response" learning tasks more slowly than do those deprived of hormone, suggesting that estrogen treatment may bias the strategy a rat is able to use to solve tasks. To determine if natural fluctuations in ovarian hormones influence cognitive strategy, we tested whether strategy use fluctuated across the estrous cycle in reproductively intact female rats. We found that in two tasks in which rats freely choose the strategy used to solve the task, rats were more likely to use place strategies at proestrous, that is, when ovarian steroids are high. Conversely, estrous rats were biased toward response strategies. The data suggest that natural fluctuations in ovarian steroids may bias the neural system used and thus the cognitive strategies chosen during learning and memory.     

New marine steroids, yonarasterols, isolated from the okinawan soft coral, Clavularia viridis

Six new marine steroids, yonarasterols A through F, were isolated from the Okinawan soft coral, Clavularia viridis. Their structures were determined based on the results of spectroscopic analysis.     

Novel steroid constituents of the soft coral Sinularia dissecta

Chemical examination of the soft coral Sinularia dissecta furnished five steroids (1-5), which include four new polyhydroxy steroids (2-5). The structures of new compounds have been established by the study of their spectral data. Steroid 5 was a novel polyoxygenated epoxy steroid.     

Steroids from the soft coral Dendronephthya sp

Fifteen steroids were isolated from the soft coral Dendronephthya sp., of which five are determined as new compounds, namely (22E)-3-O-beta-formylcholest-5,22-diene (1), (22E)-3-O-beta-formyl-24-methyl-cholest-5,22-diene (2), 2-ethoxycarbonyl-2-beta-hydroxy-A-nor-cholest-5-ene-4-one (3), (22E)-2-ethoxycarbonyl-2-beta-hydroxy-A-nor-cholest-5,22-diene-4-one (4), and (22E)-2-ethoxycarbonyl-2-beta-hydroxy-24-mthyl-A-nor-cholest-5,22-diene-4- one (5). 1 and 2 belonged to 3-O-formylated cholesterol analogues, and 3 to 5 are unique ring A-contracted steroids. Their structures were elucidated by extensive 2D NMR in association with IR, MS analysis.     

Effect of gentle nursing care of premature infants on bonding and emotional development of the child. Follow-up of premature infants in Dr. Marina Marcovich's study

The study was set out to investigate whether the Marcovich model of a "soft treatment" of premature infants encourages the parent-infant-relationship to such an extent that, at school age, the Marcovich-children would be found to differ significantly from children treated with standard care with regard to the quality of their attachment and the prevalence of emotional and behavioural disorders. The Marcovich-children of the present sample had been discharged from hospital much earlier than the standard group, they were less frequently treated with artificial respiration, infant-parent body contact was encouraged significantly earlier, and, although they were less frequently breast-fed, those who were breast-fed were allowed to do so at a much earlier stage. The Marcovich-children were found to display higher social competence, more emotional openness, more emotional coherence, less dismissal of attachment and less preoccupied anger. The two samples did not differ with regard to their total attachment quality as well as their emotional and behavioural problems. The fact that no significant differences could be established with regard to the quality of the attachment suggests that the complex life-saving attachment system is not irreversibly affected by the early separation and distress and that the months and years after the hospital stay have the power to make up with any experienced trauma. It seems, however, that special aspects of the attachment system, such as the communication and interaction, are positively encouraged and enhanced by the soft treatment of the premature infant, which leads to greater emotional openness and social competence, as well as less preoccupied anger against the attachment figures.     

Adrenal tissue in the male African catfish,Clarias gariepinus: localization and steroid hormone secretion

Interrenal-like tissue in male African catfish is localized in paired organs, situated retroperitoneally anterior of the kidney. Histological and enzyme-histochemical (3-hydroxysteroid dehydrogenase) reactions were carried out on sections of these organs in order to localize steroid-producing cells. In vitro incubations were carried out to determine the steroidogenic capacity of the interrenal-like tissue. Twenty-one steroids could be identified and quantified in the incubation medium, by means of gas chromatography followed by mass spectrometry. Cortisol, 5-and 5-androstanedione and androstenedione together comprised about 80% of the total steroid content. In a previous study, twenty testicular steroids were detected in plasma after castration. In the present investigation we have shown that most of these steroids can be produced by the interrenal-like tissue, which thus can be considered as an extra-testicular source of gonadal steroids.