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Sample records for hormonal anabolic compounds

  1. Growth hormone secretion and clearance rates in growing beef steers implanted with estrogenic anabolic compounds.

    PubMed

    Gopinath, R; Kitts, W D

    1984-01-01

    The effect of estrogenic anabolic compounds on the kinetic parameters of metabolism of growth hormone (GH) was studied in growing beef steers. Twenty-four beef steers were randomly placed into four groups and assigned to one of the following four treatment groups: zeranol, diethylstilbestrol (DES), Synovex-S and an unimplanted control. GH metabolism was studied from eight steers on day 20 following the implantation of anabolic compounds. The animals were rapidly injected with a solution of bGH (NIH-GH-B18) and the disappearance of injected GH from the plasma was monitored up to 120 min following the injection. The plasma GH disappearance curve displayed an initial rapid phase lasting 5 min and a slow disappearance phase lasting 42 min; the fractional turnover rate from the two compartments were 0.167 and 0.017 min-1, respectively. The average volume of distribution of GH in steers was 6% of the body weight. Mean values of metabolic clearance and secretion rates of GH in steers were 21 liters/h and 252 micrograms/h or 74.5 ml/kg/h and 0.91 microgram/kg/h, respectively. Steers implanted with anabolic compounds gained more rapidly (P less than 0.05) than the controls. Plasma basal GH concentration appeared to be higher in all the implanted than in the control steers. The secretion rate of GH was increased (P less than 0.05) in steers implanted with anabolic compounds when compared to control steers. The secretion rate (microgram/kg/h) was about 96% (P less than 0.05), 107% (P less than 0.05) and 81% (P less than 0.05) higher in steers implanted with DES, zeranol and Synovex-S, respectively, than in the control steers. All the compounds studied were equally effective in increasing the secretion of GH on day 20 following their implantation. Metabolic clearance rate of GH was not affected by anabolic compound implantation in steers. There was, however, a slight reduction in metabolic clearance rate due to DES and a slight elevation due to zeranol and Synovex-S when

  2. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  3. Anabolic hormone profiles in elite military men.

    PubMed

    Taylor, Marcus K; Kviatkovsky, Shiloah A; Hernández, Lisa M; Sargent, Paul; Segal, Sabrina; Granger, Douglas A

    2016-06-01

    We recently characterized the awakening responses and daily profiles of the catabolic stress hormone cortisol in elite military men. Anabolic hormones follow a similar daily pattern and may counteract the catabolic effects of cortisol. This companion report is the first to characterize daily profiles of anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in this population. Overall, the men in this study displayed anabolic hormone profiles comparable to that of healthy, athletic populations. Consistent with the cortisol findings in our prior report, summary parameters of magnitude (hormone output) within the first hour after awakening displayed superior stability versus summary parameters of pattern for both DHEA (r range: 0.77-0.82) and testosterone (r range: 0.62-0.69). Summary parameters of evening function were stable for the two hormones (both p<0.001), while the absolute decrease in testosterone across the day was a stable proxy of diurnal function (p<0.001). Removal of noncompliant subjects did not appreciably affect concentration estimates for either hormone at any time point, nor did it alter the repeatability of any summary parameter. The first of its kind, this report enables accurate estimations of anabolic balance and resultant effects upon health and human performance in this highly resilient yet chronically stressed population. Published by Elsevier Inc.

  4. [Dehydroepiandrosterone [DHEA(S)]: anabolic hormone?].

    PubMed

    Luci, Michele; Valenti, Giorgio; Maggio, Marcello

    2010-09-01

    The role of dehydroepiandrosterone (DHEA) and its sulphated form (DHEAS) as anabolic hormones is still debated in the literature. In this review we describe the fundamental steps of DHEA physiological secretion and its peripheral metabolism. Moreover we will list all the observational and intervention studies conducted in humans. Many observational studies have tested the relationship between low DHEA levels and age-related changes in skeletal muscle and bone, while intervention studies underline the positive and significant effects of DHEA treatment on several parameters of body composition. Surprisingly, observational studies are not consistent with different effects in men and women. There is recent evidence of a significant role of DHEA in frailty syndrome and as predictor of mortality. However a more complete approach of the problem suggests the opportunity to not focus only on one single hormonal derangement but to analyze the parallel dysregulation of anabolic hormones including sex steroids, GH-IGF-1 system and other catabolic hormones.

  5. Oxytocin is an anabolic bone hormone

    PubMed Central

    Tamma, Roberto; Colaianni, Graziana; Zhu, Ling-ling; DiBenedetto, Adriana; Greco, Giovanni; Montemurro, Gabriella; Patano, Nicola; Strippoli, Maurizio; Vergari, Rosaria; Mancini, Lucia; Colucci, Silvia; Grano, Maria; Faccio, Roberta; Liu, Xuan; Li, Jianhua; Usmani, Sabah; Bachar, Marilyn; Bab, Itai; Nishimori, Katsuhiko; Young, Larry J.; Buettner, Christoph; Iqbal, Jameel; Sun, Li; Zaidi, Mone; Zallone, Alberta

    2009-01-01

    We report that oxytocin (OT), a primitive neurohypophyseal hormone, hitherto thought solely to modulate lactation and social bonding, is a direct regulator of bone mass. Deletion of OT or the OT receptor (Oxtr) in male or female mice causes osteoporosis resulting from reduced bone formation. Consistent with low bone formation, OT stimulates the differentiation of osteoblasts to a mineralizing phenotype by causing the up-regulation of BMP-2, which in turn controls Schnurri-2 and 3, Osterix, and ATF-4 expression. In contrast, OT has dual effects on the osteoclast. It stimulates osteoclast formation both directly, by activating NF-κB and MAP kinase signaling, and indirectly through the up-regulation of RANK-L. On the other hand, OT inhibits bone resorption by mature osteoclasts by triggering cytosolic Ca2+ release and NO synthesis. Together, the complementary genetic and pharmacologic approaches reveal OT as a novel anabolic regulator of bone mass, with potential implications for osteoporosis therapy. PMID:19369205

  6. Oxytocin is an anabolic bone hormone.

    PubMed

    Tamma, Roberto; Colaianni, Graziana; Zhu, Ling-ling; DiBenedetto, Adriana; Greco, Giovanni; Montemurro, Gabriella; Patano, Nicola; Strippoli, Maurizio; Vergari, Rosaria; Mancini, Lucia; Colucci, Silvia; Grano, Maria; Faccio, Roberta; Liu, Xuan; Li, Jianhua; Usmani, Sabah; Bachar, Marilyn; Bab, Itai; Nishimori, Katsuhiko; Young, Larry J; Buettner, Christoph; Iqbal, Jameel; Sun, Li; Zaidi, Mone; Zallone, Alberta

    2009-04-28

    We report that oxytocin (OT), a primitive neurohypophyseal hormone, hitherto thought solely to modulate lactation and social bonding, is a direct regulator of bone mass. Deletion of OT or the OT receptor (Oxtr) in male or female mice causes osteoporosis resulting from reduced bone formation. Consistent with low bone formation, OT stimulates the differentiation of osteoblasts to a mineralizing phenotype by causing the up-regulation of BMP-2, which in turn controls Schnurri-2 and 3, Osterix, and ATF-4 expression. In contrast, OT has dual effects on the osteoclast. It stimulates osteoclast formation both directly, by activating NF-kappaB and MAP kinase signaling, and indirectly through the up-regulation of RANK-L. On the other hand, OT inhibits bone resorption by mature osteoclasts by triggering cytosolic Ca(2+) release and NO synthesis. Together, the complementary genetic and pharmacologic approaches reveal OT as a novel anabolic regulator of bone mass, with potential implications for osteoporosis therapy.

  7. Parathyroid hormone 1-34 and skeletal anabolic action

    PubMed Central

    Sanghani, A.; Coathup, M.; Briggs, T.; Bostrom, M.; Blunn, G.

    2017-01-01

    Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect. Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1. PMID:28062525

  8. Anabolic Steroids

    MedlinePlus

    Anabolic steroids are man-made substances related to male sex hormones. Doctors use anabolic steroids to treat some hormone problems in men, ... from some diseases. Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. ...

  9. Nmp4/CIZ Closes the Parathyroid Hormone Anabolic Window

    PubMed Central

    Bidwell, Joseph P.; Childress, Paul; Alvarez, Marta B.; Hood, Mark; He, Yongzheng; Pavalko, Fredrick M.; Kacena, Melissa A.; Yang, Feng-Chun

    2013-01-01

    Chronic degenerative diseases are increasing with the aging U.S. population. One consequence of this phenomenon is the need for long-term osteoporosis therapies. Parathyroid hormone (PTH), the only FDA-approved treatment that adds bone to the aged skeleton, loses its potency within two years of initial treatment but the mechanism regulating its limited “anabolic window” is unknown. We have discovered that disabling the nucleocytoplasmic shuttling transcription factor nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) in mice extends the PTH bone-forming capacity. Nmp4 was discovered during our search for nuclear matrix transcription factors that couple this hormone’s impact on osteoblast cytoskeletal and nuclear organization with its anabolic capacity. CIZ was independently discovered as a protein that associates with the focal adhesion-associated mechanosensor p130Cas. The Nmp4/CIZ-knockout (KO) skeletal phenotype exhibits a modestly enhanced bone mineral density but manifests an exaggerated response to both PTH and to BMP2 and is resistant to disuse-induced bone loss. The cellular basis of the global Nmp4/CIZ-KO skeletal phenotype remains to be elucidated but may involve an expansion of the bone marrow osteoprogenitor population along with modestly enhanced osteoblast and osteoclast activities supporting anabolic bone turnover. As a shuttling Cys2His2 zinc finger protein, Nmp4/CIZ acts as a repressive transcription factor perhaps associated with epigenetic remodeling complexes, but the functional significance of its interaction with p130Cas is not known. Despite numerous remaining questions, Nmp4/CIZ provides insights into how the anabolic window is regulated, and itself may provide an adjuvant therapy target for the treatment of osteoporosis by extending PTH anabolic efficacy. PMID:23140162

  10. Catabolic and anabolic actions of parathyroid hormone on the skeleton

    PubMed Central

    Silva, B.C.; Costa, A.G.; Cusano, N.E.; Kousteni, S.; Bilezikian, J.P.

    2015-01-01

    PTH, an 84-amino acid peptide hormone synthesized by the parathyroid glands, is essential for the maintenance of calcium homeostasis. While in its traditional metabolic role, PTH helps to maintain the serum calcium concentration within narrow, normal limits and participates as a determinant of bone remodeling, more specific actions, described as catabolic and anabolic are also well known. Clinically, the catabolic effect of PTH is best represented by primary hyperparathyroidism (PHPT), while the osteoanabolic effect of PTH is best seen when PTH or its biological aminoterminal fragment [PTH(1–34)] is used as a therapy for osteoporosis. These dual functions of PTH are unmasked under very specific pathological (PHPT) or therapeutic conditions. At the cellular level, PTH favors bone resorption, mostly by affecting the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL)-osteoprotegerin-RANK system, leading to an increase in osteoclast formation and activity. Increased bone formation due to PTH therapy is explained best by its ability to enhance osteoblastogenesis and/or osteoblast survival. The PTH-induced bone formation is mediated, in part, by a decrease in SOST/sclerostin expression in osteocytes. This review focuses on the dual anabolic and catabolic actions of PTH on bone, situations where one is enhanced over the other, and the cellular and molecular mechanisms by which these actions are mediated. PMID:21946081

  11. Anabolic hormone profiles in elite military men: Robust associations with age, stress, and fatigue.

    PubMed

    Taylor, Marcus K; Padilla, Genieleah A; Hernández, Lisa M

    2017-08-01

    We recently established stable daily profiles of the anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in 57 elite military men. In this follow-on study, we explored associations of salivary anabolic hormone profiles with demographic (i.e., age, body mass index [BMI]) and biobehavioral health indices (i.e., blood pressure, sleep, perceived stress, fatigue) via correlational models. Next, nuanced patterns were constructed using quartile splits followed by one-way analysis of variance and post hoc subgroup comparisons. Both DHEA (r range: -0.33 to -0.49) and testosterone (r range: -0.19 to -0.41) were inversely associated with age. Quartile comparisons revealed that age-related declines in DHEA were linear, curvilinear, or sigmoidal, depending on the summary parameter of interest. Anabolic hormone profiles did not associate with BMI, blood pressure, or sleep efficiency. Robust linear associations were observed between testosterone and perceived stress (r range: -0.29 to -0.36); concentration-dependent patterns were less discernible. Lower DHEA (r range: -0.22 to -0.30) and testosterone (r range: -0.22 to -0.36) concentrations associated with higher fatigue. Subsequent quartile comparisons suggested a concentration-dependent threshold with respect to evening testosterone. Specifically, those individuals within the lowest quartile (≤68.4pg/mL) endorsed the highest fatigue of the four groups (p=0.01), while the remaining three groups did not differ from each other. This study not only showed that anabolic hormone profiles have distinctive age trajectories, but are also valuable predictors of stress and fatigue in elite military men. This highlights the importance of routine monitoring of anabolic hormone profiles to sustain and optimize health and readiness in chronically stressed populations. Published by Elsevier Inc.

  12. Hormone treatment and muscle anabolism during aging: androgens.

    PubMed

    Dillon, E Lichar; Durham, William J; Urban, Randall J; Sheffield-Moore, Melinda

    2010-12-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women.

  13. Hormone Treatment and Muscle Anabolism during Aging: Androgens

    PubMed Central

    Dillon, E. Lichar; Durham, William J.; Urban, Randall J.; Sheffield-Moore, Melinda

    2010-01-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women. PMID:20452103

  14. Multiple Hormonal Deficiencies in Anabolic Hormones Are Found in Frail Older Women: The Women's Health and Aging Studies

    PubMed Central

    Xue, Qian-Li; Fried, Linda P.

    2009-01-01

    Background Alterations in anabolic hormones are theorized to contribute to aging and frailty, with most studies focusing on the relationship between individual hormones and specific age-associated diseases. We hypothesized that associations with frailty would most likely manifest in the presence of deficits in multiple anabolic hormones. Methods The relationships of serum levels of total IGF-1, DHEAS, and free testosterone (T) with frailty status (nonfrail, prefrail, or frail) were analyzed in 494 women aged 70–79 years enrolled in the Women's Health and Aging Studies I or II. Using multivariate polytomous regression, we calculated the odds of frailty for deficiency in each hormone (defined as the bottom quartile of the hormone) individually, as well as for a count of the hormones. Results For each hormone, in adjusted analyses, those with the deficiency were more likely to be frail than those without the deficiency, although this did not achieve statistical significance (IGF-1: odds ratio [OR] 1.82, confidence interval [CI] 0.81–4.08; DHEAS: OR 1.68, CI 0.77–3.69; free T: OR 2.03, CI 0.89–4.64). Compared with those with no hormonal deficiencies, those with one deficiency were not more likely to be frail (OR 1.15, CI 0.49–2.68), whereas those with two or three deficiencies had a very high likelihood of being frail (OR 2.79, CI 1.06–7.32), in adjusted models. Conclusions The absolute burden of anabolic hormonal deficiencies is a stronger predictor of frailty status than the type of hormonal deficiency, and the relationship is nonlinear. These analyses suggest generalized endocrine dysfunction in the frailty syndrome. PMID:19182229

  15. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone

    PubMed Central

    Cho, Sun Wook; Soki, Fabiana N.; Koh, Amy J.; Eber, Matthew R.; Entezami, Payam; Park, Serk In; van Rooijen, Nico; McCauley, Laurie K.

    2014-01-01

    Cellular subpopulations in the bone marrow play distinct and unexplored functions in skeletal homeostasis. This study delineated a unique role of osteal macrophages in bone and parathyroid hormone (PTH)-dependent bone anabolism using murine models of targeted myeloid-lineage cell ablation. Depletion of c-fms+ myeloid lineage cells [via administration of AP20187 in the macrophage Fas-induced apoptosis (MAFIA) mouse model] reduced cortical and trabecular bone mass and attenuated PTH-induced trabecular bone anabolism, supporting the positive function of macrophages in bone homeostasis. Interestingly, using a clodronate liposome model with targeted depletion of mature phagocytic macrophages an opposite effect was found with increased trabecular bone mass and increased PTH-induced anabolism. Apoptotic cells were more numerous in MAFIA versus clodronate-treated mice and flow cytometric analyses of myeloid lineage cells in the bone marrow showed that MAFIA mice had reduced CD68+ cells, whereas clodronate liposome-treated mice had increased CD68+ and CD163+ cells. Clodronate liposomes increased efferocytosis (clearance of apoptotic cells) and gene expression associated with alternatively activated M2 macrophages as well as expression of genes associated with bone formation including Wnt3a, Wnt10b, and Tgfb1. Taken together, depletion of early lineage macrophages resulted in osteopenia with blunted effects of PTH anabolic actions, whereas depletion of differentiated macrophages promoted apoptotic cell clearance and transformed the bone marrow to an osteogenic environment with enhanced PTH anabolism. These data highlight a unique function for osteal macrophages in skeletal homeostasis. PMID:24406853

  16. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone.

    PubMed

    Cho, Sun Wook; Soki, Fabiana N; Koh, Amy J; Eber, Matthew R; Entezami, Payam; Park, Serk In; van Rooijen, Nico; McCauley, Laurie K

    2014-01-28

    Cellular subpopulations in the bone marrow play distinct and unexplored functions in skeletal homeostasis. This study delineated a unique role of osteal macrophages in bone and parathyroid hormone (PTH)-dependent bone anabolism using murine models of targeted myeloid-lineage cell ablation. Depletion of c-fms(+) myeloid lineage cells [via administration of AP20187 in the macrophage Fas-induced apoptosis (MAFIA) mouse model] reduced cortical and trabecular bone mass and attenuated PTH-induced trabecular bone anabolism, supporting the positive function of macrophages in bone homeostasis. Interestingly, using a clodronate liposome model with targeted depletion of mature phagocytic macrophages an opposite effect was found with increased trabecular bone mass and increased PTH-induced anabolism. Apoptotic cells were more numerous in MAFIA versus clodronate-treated mice and flow cytometric analyses of myeloid lineage cells in the bone marrow showed that MAFIA mice had reduced CD68(+) cells, whereas clodronate liposome-treated mice had increased CD68(+) and CD163(+) cells. Clodronate liposomes increased efferocytosis (clearance of apoptotic cells) and gene expression associated with alternatively activated M2 macrophages as well as expression of genes associated with bone formation including Wnt3a, Wnt10b, and Tgfb1. Taken together, depletion of early lineage macrophages resulted in osteopenia with blunted effects of PTH anabolic actions, whereas depletion of differentiated macrophages promoted apoptotic cell clearance and transformed the bone marrow to an osteogenic environment with enhanced PTH anabolism. These data highlight a unique function for osteal macrophages in skeletal homeostasis.

  17. Bone-targeting parathyroid hormone conjugates outperform unmodified PTH in the anabolic treatment of osteoporosis in rats.

    PubMed

    Yang, Yang; Aghazadeh-Habashi, Ali; Panahifar, Arash; Wu, Yuchin; Bhandari, Krishna H; Doschak, Michael R

    2017-08-01

    Synthetic parathyroid hormone (PTH) is clinically indicated for the treatment of osteoporosis, through its anabolic effects on parathyroid hormone receptors (PTHRs), located on osteoblast cells. However, the bioavailability of PTH for bone cells is restricted by the short half-life of PTH and the widespread distribution of PTHRs in non-skeletal tissues. To impart affinity for mineralized bone surfaces, bisphosphonate (BP)-mediated PTH analogues were synthesized, characterized, and evaluated in vitro and in vivo. The successful synthesis of PTH-PEG-BP was identified on MALDI-ToF mass spectra; bone-targeting potential was evaluated by hydroxyapatite binding test; and receptor bioactivity was assessed in UMR-106 (rat osteosarcoma) cells that constitutively express PTHRs. Therapeutic efficacy was evaluated using ovariectomized rats that remained untreated for 8 weeks to allow development of osteopenia. Those rats then received daily subcutaneous injections of PTH-PEG-BP, thiol-BP vehicle, or unmodified PTH, and compared to sham-operated healthy rats at 0, 4, 8, 12, and 16 weeks. In vivo micro-CT was conducted on the proximal tibial metaphysis to measure microstructural bone parameters, and new bone formation was detected using dynamic labeling. Bone strength was assessed using three-point bending mechanical testing. Our study determined that PTH-PEG-BP conjugates significantly enhanced PTH targeting to the bone matrix while retaining full PTH bioactivity. Moreover, PTH-PEG-BP conjugates significantly increased trabecular bone quality, anabolic bone formation, and improved bone strength over systemically administered PTH alone. We highlight the promise of a novel class of bone-targeting anabolic compound for the treatment of osteoporosis and related bone disorders.

  18. Amphiregulin lacks an essential role for the bone anabolic action of parathyroid hormone.

    PubMed

    Jay, Freya F; Vaidya, Mithila; Porada, Sabrina M; Andrukhova, Olena; Schneider, Marlon R; Erben, Reinhold G

    2015-12-05

    Although parathyroid hormone (PTH) has long been known to act as a bone anabolic agent when administered intermittently, the exact underlying mechanisms remain largely unknown. Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, has been identified to be a PTH target gene in vitro and in vivo. Here, we used female global AREG knockout (AREG-KO) mice to explore the role of AREG in mediating the bone anabolic effects of PTH. AREG-KO mice were characterized by unchanged distal femoral cancellous bone mass and only subtle decreases in bone mineral density (BMD) and cortical thickness at the femoral midshaft at 3 and 8 months of age, relative to wildtype controls. AREG deficiency was associated with complex changes in the mRNA expression of other EGFR ligands in femoral cancellous bone osteoblasts in situ in 3-week-old mice. To examine the bone anabolic effects of PTH in the absence and presence of AREG, we injected 3-month-old AREG-KO females and wildtype control littermates with 80 μg/kg PTH or vehicle 5 times per week over 4 weeks. Intermittent PTH treatment of AREG-KO mice led to increases in femoral trabecular and cortical BMD, cortical thickness, endocortical and periosteal bone formation, cancellous bone formation rate, and serum osteocalcin, comparable to those observed in wildtype control mice. In conclusion, our data indicate that the bone anabolic effects of PTH do not require AREG, at least in 3-month-old female mice. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?

    PubMed

    Tentori, Lucio; Graziani, Grazia

    2007-05-01

    Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

  20. Growth and anabolic hormones, leptin, and neuromuscular performance in moderately trained prepubescent athletes and untrained boys.

    PubMed

    Tsolakis, Charilaos; Vagenas, George; Dessypris, Athanasios

    2003-02-01

    We investigated hormonal regulators of growth and development, leptin levels, body composition, neuromuscular performance, and the associations among them in trained prepubertal athletes (experimental group [EG]) and an untrained control group (CG). Informed consent was obtained from the children and their parents. Their maturation stage was evaluated according to Tanner's criteria. There were no differences between EG and CG in physical characteristics, body mass index (BMI), lean body mass, testosterone (T), sex hormone-binding globulin, free androgen index, growth hormone (GH), hand grip strength, and jumping performance. Leptin levels and percent fat of the EG were significantly lower than those of the CG (p < 0.05-0.005). Leptin levels were significantly correlated to body fat and BMI for both the EG and the CG (r = 0.51-0.79). There is little evidence that leptin has a positive effect on growth and anabolic factors. Sex hormone-binding globulin and GH may explain the variation of leptin in athletes with low T (R(2) = 0.43) and in CG (R(2) = 0.35), respectively. Leptin seems to be a permissive factor for the onset of puberty, and the training background needs an optimal biological maturation to produce significant differences in muscle and power performance.

  1. Role of fibroblast growth factor 2 and Wnt signaling in anabolic effects of parathyroid hormone on bone formation

    PubMed Central

    Fei, Yurong; Hurley, Marja M.

    2012-01-01

    Osteoporosis poses enormous health and economic burden worldwide. One of the very few anabolic agents for osteoporosis is parathyroid hormone (PTH). Although great progress has been made since the FDA approved PTH in 2002, the detailed mechanisms of the bone anabolic effects of intermittent PTH treatment is still not well understood. PTH bone anabolic effect is regulated by extracellular factors. Maximal bone anabolic effect of PTH requires fibroblast growth factor 2 (FGF2) signaling, which might be mediated by transcription factor activating transcription factor 4 (ATF4). Maximal bone anabolic effect of PTH also requires Wnt signaling. Particularly, Wnt antagonists such as sclerostin, dickkopf 1 (DKK1) and secreted frizzled related protein 1 (sFRP1) are promising targets to increase bone formation. Interestingly, FGF2 signaling modulates Wnt/β-Catenin signaling pathway in bone. Therefore, multiple signaling pathways utilized by PTH are cross talking and working together to promote bone formation. Extensive studies on the mechanisms of action of PTH will help to identify new pathways that regulate bone formation, to improve available agents to stimulate bone formation, and to identify potential new anabolic agents for osteoporosis. PMID:22378151

  2. Role of fibroblast growth factor 2 and Wnt signaling in anabolic effects of parathyroid hormone on bone formation.

    PubMed

    Fei, Yurong; Hurley, Marja M

    2012-11-01

    Osteoporosis poses enormous health and economic burden worldwide. One of the very few anabolic agents for osteoporosis is parathyroid hormone (PTH). Although great progress has been made since the FDA approved PTH in 2002, the detailed mechanisms of the bone anabolic effects of intermittent PTH treatment is still not well understood. PTH bone anabolic effect is regulated by extracellular factors. Maximal bone anabolic effect of PTH requires fibroblast growth factor 2 (FGF2) signaling, which might be mediated by transcription factor activating transcription factor 4 (ATF4). Maximal bone anabolic effect of PTH also requires Wnt signaling. Particularly, Wnt antagonists such as sclerostin, dickkopf 1 (DKK1) and secreted frizzled related protein 1 (sFRP1) are promising targets to increase bone formation. Interestingly, FGF2 signaling modulates Wnt/β-Catenin signaling pathway in bone. Therefore, multiple signaling pathways utilized by PTH are cross talking and working together to promote bone formation. Extensive studies on the mechanisms of action of PTH will help to identify new pathways that regulate bone formation, to improve available agents to stimulate bone formation, and to identify potential new anabolic agents for osteoporosis. Copyright © 2012 Wiley Periodicals, Inc.

  3. Effects of anabolic steroid (19-nortestosterone) on the secretion of testicular hormones in the stallion.

    PubMed

    Nagata, S; Kurosawa, M; Mima, K; Nambo, Y; Fujii, Y; Watanabe, G; Taya, K

    1999-03-01

    The aim of this study was to clarify the effect of anabolic steroids on the testicular endocrine function of mature stallions. Mature thoroughbred stallions were treated with 800 mg nandrolone decanoate every 3 weeks for 3 months. After the first treatment, plasma concentrations of LH, immunoreactive inhibin and testosterone decreased rapidly to the nadir. These hormones were maintained at significantly lower concentrations compared with concentrations in intact stallions. Histology of the testicular tissue indicated the arrest of advanced spermatogenesis in the seminiferous tubules and a severe depletion of the number of Leydig cells in the interstitial compartment as a result of treatment. Most of the immunopositive cells for the inhibin alpha-subunit and steroidogenesis enzymes in the interstitial compartment decreased below detectable amounts, whereas immunopositive reactions of inhibin alpha-subunit in the seminiferous tubules were clearly observed. In conclusion, the treatment of mature stallions with nandrolone decanoate caused a decrease in the secretion of ir-inhibin and testosterone from the testis, the depletion of the number of Leydig cells and a decrease below detectable amounts of inhibin alpha-subunit and steroidogenesis enzymes. The concentration of ir-inhibin in the peripheral blood may be a useful marker for the examination of testicular activity in stallions being treated with anabolic steroids.

  4. Non-targeted acquisition strategy for screening doping compounds based on GC-EI-hybrid quadrupole-Orbitrap mass spectrometry: A focus on exogenous anabolic steroids.

    PubMed

    de Albuquerque Cavalcanti, Gustavo; Rodrigues, Lucas Martins; Dos Santos, Leonardo; Zheng, Xin; Gujar, Amit; Cole, Jason; Padilha, Monica Costa; de Aquino Neto, Francisco Radler

    2017-06-10

    This is a first look at a non-targeted screening method based on Orbitrap gas chromatography-mass spectrometry (GC-MS) technology for a large number of banned compounds in sports found in urine, including exogenous anabolic steroids, β-agonists, narcotics, stimulants, hormone modulators, and diuretics. A simple sample preparation was processed in four steps: an enzymatic hydrolysis, liquid-liquid extraction, evaporation, and trimethylsilylation. All compounds were able to meet the World Anti-Doping Agency's sensitivity criteria with mass accuracies less than 1 ppm and with sufficient points across the peak by running the Orbitrap GC-MS in full-scan mode. In addition, we discuss our initial findings of using a full-scan selected ion monitoring-tandem mass spectrometry (SIM-MS/MS) approach as a way to obtain lower detection limits and reach desirable selectivity for some exogenous anabolic steroids. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor.

    PubMed

    Bauer, E R; Daxenberger, A; Petri, T; Sauerwein, H; Meyer, H H

    2000-12-01

    For the steroidal growth promoters trenbolone acetate (TBA) and melengestrol acetate (MGA) neither the complete spectrum of biological activities nor the potential endocrine disrupting activity of their excreted metabolites in the environment is fully understood. The potency of these substances in [3H]dihydrotestosterone ([3H]-DHT) displacement from the recombinant human androgen receptor (rhAR) and from human sex-hormone binding globulin (hSHBG) was evaluated. In addition, the potency for [3H]-ORG2058 displacement from the bovine uterine progestin receptor (bPR) was tested. For comparison, different anabolics and synthetic hormones were also tested for their binding affinities. For 17beta-trenbolone (17beta-TbOH), the active compound after TBA administration, an affinity the rhAR similar to dihydrotestosterone (DHT) and a slightly higher affinity to the bPR than progesterone were demonstrated. The affinity of the two major metabolites, 17alpha-trenbolone and trendione, was reduced to less than 5% of the 17beta-TbOH-value. The affinity of these three compounds and of MGA to the hSHBG was much lower compared with DHT. MGA showed a 5.3-fold higher affinity than progesterone to the bPR but only a weak affinity to the rhAR. The major MGA metabolites have an affinity to the bPR between 85% and 28% of the affinity of progesterone. In consequence, MGA and TBA metabolites may be hormonally active substances, which will be present in edible tissues and in manure. We conclude that detailed investigations on biodegradation, distribution and bio-efficacy of these substances are necessary.

  6. Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height.

    PubMed

    Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

    2012-04-01

    Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin(®)) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.

  7. An association between bone mineral density and anabolic hormones in middle-aged and elderly men with prediabetes.

    PubMed

    Rabijewski, Michał; Papierska, Lucyna; Piątkiewicz, Paweł

    2017-09-01

    Prediabetes (PD) leads to reduced testosterone (T) in males, but the association between the anabolic hormones and bone mineral density (BMD) remains unknown. We investigated an association between the anabolic hormones and BMD in middle-aged and elderly men with PD. We investigated 84 prediabetic and 56 control men. Total T (TT), calculated free T (cFT), and dehydroepiandrosterone sulfate (DHEAS) were measured, and BMD was assessed using DXA methods. Patients with PD had lower TT (p < .001), cFT (p < .005), and DHEAS (p < .02) than control group. BMD values of the lower lumbar spine (p < .02) and total body (p < .05) in prediabetic men were lower than in control group. Lumbar spine BMD correlated with TT (r = 0.376), cFT (r = 0.235), and HbA1c (r = -0.368); femoral neck BMD correlated with TT (r = 0.412) and cFT (r = 0.421). The high lumbar spine and femur neck BMD was associated with high TT, cFT, and low HbA1c, while the high total body BMD with high TT, cFT, and low HbA1c. The anabolic hormones significantly affect BMD in male with PD, and screening for low BMD is necessary in these patients.

  8. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  9. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  10. Anabolic steroids.

    PubMed

    Mottram, D R; George, A J

    2000-03-01

    Anabolic steroids are synthetic derivatives of testosterone modified to enhance the anabolic rather than the androgenic actions of the hormone. The anabolic effects are considered to be those promoting protein synthesis, muscle growth and crythopoiesis. There are numerous side-effects to anabolic steroids, including hypertension and atherosclerosis, blood clotting, jaundice, hepatic carcinoma, tendon damage, psychiatric and behavioural effects and, in males, reduced fertility and gynaccomastia. Anabolic steroids were added to the International Olympic Committee's list of banned substances in 1975. The majority of 'evidence' concerning the efficacy of anabolic steroids as performance enhancing agents is anecdotal. In the main, experimental investigations have been poorly designed scientifically, clinically and statistically. The percentage of positive test results from IOC accredited laboratories has remained consistently low. However, athletes take their steroids during training and out-of-competition testing is not conducted in all countries, although international co-operation is now under consideration. Despite the lack of conclusive evidence, steroids users will continue to hold the view that their effects are efficacious and they are therefore unlikely to be persuaded to curtail their use.

  11. Biochemistry and physiology of anabolic hormones used for improvement of meat production.

    PubMed

    Meyer, H H

    2001-01-01

    A number of hormones are involved in endocrine regulation of growth. In general, these hormones enhance body protein accretion and metabolise fat stores resulting in increased lean growth rates. Most practical importance was obtained by sex hormones (oestrogens and androgens), beta-agonists and growth hormone - whether legally or illegally. Efficiency of growth promotion ranges between 0% and +20% depending on the prerequisites such as species, breed, gender, age, reproductive status, body score or feeding of the animals. Oestrogens and androgens mediate their activity via intracellular receptors - directly in muscular tissue as well as indirectly via stimulation of growth hormone from the hypophysis and other growth factors from liver plus several further organs. In addition, mineral absorption in the gut is improved. The outstanding efficiency of trenbolone is based on its androgenic plus antiglucocorticoid activity. Melengestrolacetate is thought to act indirectly via stimulation of endogenous ovarian oestradiol in non-pregnant heifers. The necessary dosages and residue formations depend on the pharmacokinetic parameters of each substance and extrapolations between compounds are hardly possible. Growth hormone and beta2-agonists use independent pathways for growth promotion not related to steroid biochemistry.

  12. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    SciTech Connect

    Lu, Jinxiu; Cheng, Henry; Atti, Elisa; Shih, Diana M.; Demer, Linda L.; Tintut, Yin

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  13. Effect of 2 days of intensive resistance training on appetite-related hormone and anabolic hormone responses.

    PubMed

    Goto, Kazushige; Shioda, Kohei; Uchida, Sunao

    2013-03-01

    This study was designed to determine endocrine responses during 2 days of strenuous resistance training. Ten healthy men performed resistance training twice a day for two successive days to induce acute fatigue (excessive physical stress). The resistance training consisted of four exercises for the lower body in the morning and seven exercises for the upper body in the afternoon. Maximal isometric and isokinetic strengths were measured from day 1 (before the training period) to day 3 (after the training period). Fasting blood samples were taken on days 1-3. Maximal isometric and isokinetic strengths significantly decreased with two successive days of training (P<0·05), with significant increases in serum creatine phosphokinase and myoglobin concentrations (P<0·05). Significant reductions in the fasting concentrations of serum insulin-like growth factor-1, free testosterone, insulin and high-molecular-weight adiponectin were observed on day 3 (P<0·05), whereas there were no changes in the serum cortisol concentration or the free testosterone/cortisol ratio. Plasma active ghrelin and serum leptin concentrations decreased by -20·7 ± 2·8% and -29·6 ± 4·1%, respectively (P<0·05). Two days strenuous resistance training significantly affects the profiles of anabolic hormone and endocrine regulators of appetite and energy balance, such as ghrelin and leptin. The present findings suggest that decreased ghrelin and leptin concentrations might reflect excessive physical stress and may be early signs of accumulated fatigue. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  14. Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies.

    PubMed

    Esbrit, Pedro; Alcaraz, María José

    2013-05-15

    Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorptive drugs. An alternative therapeutic approach for osteoporosis is currently available, based on the intermittent administration of parathyroid hormone (PTH). Bone anabolism caused by PTH therapy is mainly accounted for by the ability of PTH to increase osteoblastogenesis and osteoblast survival. PTH and PTH-related protein (PTHrP)-an abundant local factor in bone- interact with the common PTH type 1 receptor with similar affinities in osteoblasts. Studies mainly in osteoporosis rodent models and limited data in postmenopausal women suggest that N-terminal PTHrP peptides might be considered a promising bone anabolic therapy. In addition, putative osteogenic actions of PTHrP might be ascribed not only to its N-terminal domain but also to its PTH-unrelated C-terminal region. In this review, we discuss the underlying cellular and molecular mechanisms of the anabolic actions of PTH and the similar potential of PTH-related protein (PTHrP) to increase bone mass and improve bone regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. [Effect of anabolic preparation fenobolin on blood, reproductive system and hormone levels in blood serum of fractionally irradiated male rats].

    PubMed

    Vereshchako, G G; Gorokh, G A; Fedosenko, O L; Gun'kova, N V; Iakushev, D L; Konoplia, E F

    2011-01-01

    Influence of anabolic drug (phenobolin) injection at a dose of 2.5 mg/kg on some indexes of blood, reproductive system, the level of thyroid hormones, corticosterone and testosterone in blood serum of the male rats exposed to a fractional irradiation at the total dose of 2.0 Gy have been studied. A significant decrease in the quantity of leucocytes and lymphocytes after a fractional irradiation without and with phenobolin introduction was determined. Introduction of anabolic drug resulted in a significant drop of relative mass of testes and, particularly, epididymes, and also in a sharp decrease of the number of mature germ cells isolated from epididymes. A combined action of phenobolin and fractional irradiation (2.0 Gy) led to a significant reduction (3-5 times) in the quantity of mature germ cells in an epididymis. In some cases phenobolin influenced the level of testosterone in blood serum of the intact and irradiated animals. The anabolic steroid drug affects negatively the state of reproductive system of male rats.

  16. Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy.

    PubMed

    Oishi, Yoshimi; Tsukamoto, Hayato; Yokokawa, Takumi; Hirotsu, Keisuke; Shimazu, Mariko; Uchida, Kenji; Tomi, Hironori; Higashida, Kazuhiko; Iwanaka, Nobumasa; Hashimoto, Takeshi

    2015-03-15

    We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals.

  17. Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

    PubMed

    Clifton, Kari B; Conover, Cheryl A

    2015-12-01

    Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice.

  18. Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin.

    PubMed

    Bonnet, Nicolas; Conway, Simon J; Ferrari, Serge L

    2012-09-11

    Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn(-/-) and Postn(+/+) mice to intermittent PTH. Compared with Postn(+/+), Postn(-/-) mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in Postn(-/-) mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-β-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (TOPGAL;Postn(-/-) mice). PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin αVβ3 receptor, whereas periostin-blocking antibody prevented inhibition of MEF2C and Sost by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in Postn(-/-) mice. In addition, primary osteoblasts from Postn(-/-) mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of Postn(-/-) osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-β-catenin signaling, and osteoblast differentiation.

  19. Inflammation marker, damage marker and anabolic hormone responses to resistance training with vascular restriction in older males.

    PubMed

    Karabulut, Murat; Sherk, Vanessa D; Bemben, Debra A; Bemben, Michael G

    2013-09-01

    The goal of this study was to examine anabolic hormone, muscle damage marker and inflammation marker responses to two types of resistance training protocols in older men. Thirty-six healthy older males (mean age = 56.6 ± 0.6 years) completed 6 weeks of high-intensity resistance training (HI-RT), low-intensity resistance training with vascular restriction (LI-BFR) or no exercise control group (CON) three times per week. Three upper body exercises were performed by both exercise groups at the same intensity (at 80% 1-RM), but lower body exercises were performed by the HI-RT group at 80% 1-RM and by the LI-BFR group at 20% 1-RM with vascular restriction. Resting serum creatine kinase (CK), interleukin 6 (IL-6), insulin-like growth factor-I (IGF-I), IGF binding protein 3 (IGFBP-3) and testosterone (T) were measured before and after training. No significant group differences in resting CK, IL-6, IGF-I, IGFBP-3 and T were detected following training (P>0.05). In addition, there were no significant changes in muscle cross-sectional area (CSA), but a trend for significant decreases in the percent changes in thigh subcutaneous fat (P = 0.051). Although training-induced anabolic hormone response did not reach statistical significance, our findings on CK and IL-6 indicated that the LI-BFR training protocol was safe and well tolerated for older men to perform to improve muscular strength. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  20. Anabolic and catabolic hormones and energy balance of the male bodybuilders during the preparation for the competition.

    PubMed

    Mäestu, Jarek; Eliakim, Alon; Jürimäe, Jaak; Valter, Ivo; Jürimäe, Toivo

    2010-04-01

    The purpose of the study was to investigate simultaneous effects of energy balance, caloric intake, and the hormonal anabolic-catabolic balance in bodybuilders prior to competition. Fourteen male bodybuilders took part in an 11-week energy-restricted period to reduce body fat. The subjects were divided into the energy-restricted group (ERG) (n = 7), who were preparing for the competition, or the control group (CG) (n = 7) who continued to train regularly and did not change their dietary or training pattern. Participants were tested at 11 weeks (T1), 5 weeks (T2), and 3 days (T3) before competition for diet, body composition, and fasting hormonal assessment. Body mass and body fat percentage of ERG were significantly (p < 0.05) decreased during the study period. In ERG, insulinlike growth factor-1 (IGF-1) and insulin decreased significantly during the 11-week weight-reduction period (p < 0.05). Testosterone was decreased only from week 11 to week 5 (from 20.3 +/- 6.0 to 18.0 +/- 6.8 nmol/L). Changes in IGF-I concentration were significantly related to changes in insulin (r = 0.741), fat mass (r = 0.705), lean body mass (r = 0.696), and body mass (r = 0.652). Changes in insulin concentrations were significantly related to changes in fat mass (r = 0.630) and lean body mass (r = 0.725). These data indicate that severe energy restriction to extremely low body energy reserves decreases significantly the concentrations of 3 anabolic pathways despite high protein intake. Monitoring of insulin and IGF-1 concentration is suggested to prevent losses in muscle mass in energy-restricted conditions. Other nutritional strategies might be needed to prevent possible catabolic effect during preparation of bodybuilders to competition.

  1. Are Osteoclasts Needed for the Bone Anabolic Response to Parathyroid Hormone?

    PubMed Central

    Pierroz, Dominique D.; Bonnet, Nicolas; Baldock, Paul A.; Ominsky, Michael S.; Stolina, Marina; Kostenuik, Paul J.; Ferrari, Serge L.

    2010-01-01

    PTH stimulates osteoblastic cells to form new bone and to produce osteoblast-osteoclast coupling factors such as RANKL. Whether osteoclasts or their activity are needed for PTH anabolism remains uncertain. We treated ovariectomized huRANKL knock-in mice with a human RANKL inhibitor denosumab (DMAb), alendronate (Aln), or vehicle for 4 weeks, followed by co-treatment with intermittent PTH for 4 weeks. Loss of bone mass and microarchitecture was prevented by Aln and further significantly improved by DMAb. PTH improved bone mass, microstructure, and strength, and was additive to Aln but not to DMAb. Aln inhibited biochemical and histomorphometrical indices of bone turnover, -i.e. osteocalcin and bone formation rate (BFR) on cancellous bone surfaces-, and Dmab inhibited them further. However Aln increased whereas Dmab suppressed osteoclast number and surfaces. PTH significantly increased osteocalcin and bone formation indices, in the absence or presence of either antiresorptive, although BFR remained lower in presence of Dmab. To further evaluate PTH effects in the complete absence of osteoclasts, high dose PTH was administered to RANK−/− mice. PTH increased osteocalcin similarly in RANK−/− and WT mice. It also increased BMD in RANK−/− mice, although less than in WT. These results further indicate that osteoclasts are not strictly required for PTH anabolism, which presumably still occurs via stimulation of modeling-based bone formation. However the magnitude of PTH anabolic effects on the skeleton, in particular its additive effects with antiresorptives, depends on the extent of the remodeling space, as determined by the number and activity of osteoclasts on bone surfaces. PMID:20558734

  2. Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor signaling in osteocytes.

    PubMed

    Rhee, Yumie; Lee, Eun-Young; Lezcano, Virginia; Ronda, Ana C; Condon, Keith W; Allen, Matthew R; Plotkin, Lilian I; Bellido, Teresita

    2013-10-11

    The contribution of remodeling-based bone formation coupled to osteoclast activity versus modeling-based bone formation that occurs independently of resorption, to the anabolic effect of PTH remains unclear. We addressed this question using transgenic mice with activated PTH receptor signaling in osteocytes that exhibit increased bone mass and remodeling, recognized skeletal effects of PTH elevation. Direct inhibition of bone formation was accomplished genetically by overexpressing the Wnt antagonist Sost/sclerostin; and resorption-dependent bone formation was inhibited pharmacologically with the bisphosphonate alendronate. We found that bone formation induced by osteocytic PTH receptor signaling on the periosteal surface depends on Wnt signaling but not on resorption. In contrast, bone formation on the endocortical surface results from a combination of Wnt-driven increased osteoblast number and resorption-dependent osteoblast activity. Moreover, elevated osteoclasts and intracortical/calvarial porosity is exacerbated by overexpressing Sost and reversed by blocking resorption. Furthermore, increased cancellous bone is abolished by Wnt inhibition but further increased by blocking resorption. Thus, resorption induced by PTH receptor signaling in osteocytes is critical for full anabolism in cortical bone, but tempers bone gain in cancellous bone. Dissecting underlying mechanisms of PTH receptor signaling would allow targeting actions in different bone compartments, enhancing the therapeutic potential of the pathway.

  3. Resorption Controls Bone Anabolism Driven by Parathyroid Hormone (PTH) Receptor Signaling in Osteocytes*

    PubMed Central

    Rhee, Yumie; Lee, Eun-Young; Lezcano, Virginia; Ronda, Ana C.; Condon, Keith W.; Allen, Matthew R.; Plotkin, Lilian I.; Bellido, Teresita

    2013-01-01

    The contribution of remodeling-based bone formation coupled to osteoclast activity versus modeling-based bone formation that occurs independently of resorption, to the anabolic effect of PTH remains unclear. We addressed this question using transgenic mice with activated PTH receptor signaling in osteocytes that exhibit increased bone mass and remodeling, recognized skeletal effects of PTH elevation. Direct inhibition of bone formation was accomplished genetically by overexpressing the Wnt antagonist Sost/sclerostin; and resorption-dependent bone formation was inhibited pharmacologically with the bisphosphonate alendronate. We found that bone formation induced by osteocytic PTH receptor signaling on the periosteal surface depends on Wnt signaling but not on resorption. In contrast, bone formation on the endocortical surface results from a combination of Wnt-driven increased osteoblast number and resorption-dependent osteoblast activity. Moreover, elevated osteoclasts and intracortical/calvarial porosity is exacerbated by overexpressing Sost and reversed by blocking resorption. Furthermore, increased cancellous bone is abolished by Wnt inhibition but further increased by blocking resorption. Thus, resorption induced by PTH receptor signaling in osteocytes is critical for full anabolism in cortical bone, but tempers bone gain in cancellous bone. Dissecting underlying mechanisms of PTH receptor signaling would allow targeting actions in different bone compartments, enhancing the therapeutic potential of the pathway. PMID:23963454

  4. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

    NASA Technical Reports Server (NTRS)

    Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

    2002-01-01

    Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

  5. Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin

    PubMed Central

    Bonnet, Nicolas; Conway, Simon J.; Ferrari, Serge L.

    2012-01-01

    Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn−/− and Postn+/+ mice to intermittent PTH. Compared with Postn+/+, Postn−/− mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in Postn−/− mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-β-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (TOPGAL;Postn−/− mice). PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin αVβ3 receptor, whereas periostin-blocking antibody prevented inhibition of MEF2C and Sost by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in Postn−/− mice. In addition, primary osteoblasts from Postn−/− mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of Postn−/− osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-β-catenin signaling, and osteoblast differentiation. PMID:22927401

  6. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

    NASA Technical Reports Server (NTRS)

    Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

    2002-01-01

    Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

  7. Long-chain n-3 fatty acids - New anabolic compounds improving protein metabolism

    USDA-ARS?s Scientific Manuscript database

    Previous animal studies demonstrated that chronic feeding of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) that modifies muscle membrane fatty acid composition promotes protein anabolism by blunting the age-associated deterioration in insulin sensitivity. The current study assessed, as a pr...

  8. Anabolic-androgenic steroids and related substances.

    PubMed

    Yesalis, Charles E; Bahrke, Michael S

    2002-08-01

    Testosterone is the primary male sex hormone, and anabolic-androgenic steroids are synthetic derivatives of testosterone. Anabolic steroids are used to enhance athletic performance and appearance. Adverse effects include those on the liver, serum lipids, psyche/behavior, and the reproductive system. Androstenedione is an anabolic-androgenic steroid used to increase blood testosterone levels for the purposes of increasing strength, lean body mass, and sexual performance. However, there is no research indicating androstenedione or its related compounds, significantly increases strength and/or lean body mass by increasing testosterone levels. The long-term health effects of prolonged androstenedione supplementation are unknown. Dehydroepiandrosterone (DHEA) is a weak androgen also used to elevate testosterone levels. DHEA is also advertised as an antiobesity and antiaging supplement capable of improving libido, vitality, and immunity levels. However, research demonstrates that DHEA supplementation does not increase serum testosterone concentrations or increase strength in men, and it may have virilizing effects on women.

  9. Treatment of idiopathic short stature: effects of gonadotropin-releasing hormone analogs, aromatase inhibitors and anabolic steroids.

    PubMed

    Dunkel, Leo

    2011-01-01

    Modulation of sex steroid action on the growth plate can, at least theoretically, increase adult height in children and adolescents with idiopathic short stature. Gonadotropin-releasing hormone (GnRH) analog therapy during adolescence has been shown effective in a placebo-controlled study, but to obtain clinically significant increases in adult height, the treatment duration must be lengthy (several years). Furthermore, such treatment seems to compromise bone health and, because of the resulting delay in pubertal development, likely has psychosocial consequences. Therefore, GnRH analogs are no longer recommended to augment height in adolescents with short stature and normally timed puberty. Aromatase inhibitors are probably more effective than GnRH analogs in promoting increased adult height in children with short stature and, unlike GnRH analogs, do not delay pubertal development in males. However, due to a dearth of safety data with aromatase inhibitors for the treatment of short stature, their use outside a research setting is currently not recommended. Positive effects of anabolic steroids on adult height have not been documented.

  10. 17β-trenbolone, an anabolic-androgenic steroid as well as an environmental hormone, contributes to neurodegeneration.

    PubMed

    Ma, Fucui; Liu, Daicheng

    2015-01-01

    Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic-androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in the hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles in neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down the onset of neurodegenerative disorders.

  11. Anabolic effects of PTH and the 'anabolic window'.

    PubMed

    Pazianas, Michael

    2015-03-01

    Maximization of the anabolic effects of intermittent administration of parathyroid hormone (PTH) has recently been at the forefront of clinical research in the area of osteoporosis, with the 'anabolic window' concept as its main driving force. The outcome of these attempts, however, has not been encouraging. This article examines whether the concept itself is based on sound evidence, related pathophysiological aspects, and whether the new anti-sclerostin antibodies could have extended anabolic action. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Interactions of anabolic steroids.

    PubMed

    Kopera, H

    1993-01-01

    Drug-drug interactions, or interference between drugs and other treatments, depend on many factors and are therefore difficult to predict. However, a number are clearly established in the case of anabolic-androgenic steroids. The beneficial interactions between anabolic steroids and radiotherapy or cytostatic drugs respectively are of therapeutic value. Adjuvant treatment with anabolic compounds in patients undergoing radiation and/or cytostatic therapy is beneficial because it can prevent or reduce depression of erythropoiesis, granulopoiesis and thrombopoiesis. It also diminishes protein catabolism, supports recovery, improves the general condition of the patient and minimizes radiation sickness. Potentially adverse interactions with anabolic steroids must be expected in the case of oral anticoagulants and antidiabetic drugs, since sensitivity to each of the latter is increased. This makes it particularly advisable to monitor patients receiving either oral anticoagulants or antidiabetic treatment concurrently with anabolic drugs.

  13. Skeletal Response of Male Mice to Anabolic Hormone Therapy in the Absence of the Igfals Gene

    PubMed Central

    Kennedy, Oran D.; Sun, Hui; Wu, YingJie; Courtland, Hayden-William; Williams, Garry A.; Cardoso, Luis; Basta-Pljakic, Jelena; Schaffler, Mitchell B.

    2014-01-01

    IGF-I is a critical regulator of skeletal acquisition, which acts in endocrine and autocrine/paracrine modes. In serum, IGF-I is carried by the IGF-binding proteins in binary complexes. Further stabilization of these complexes is achieved by binding to the acid labile subunit (ALS) in a ternary complex (of IGF-I-IGF-binding protein 3/5-ALS). Ablation of the Igfals gene in humans (ALS deficiency) and mice (ALS knockout [ALSKO]) leads to markedly decreased serum IGF-I levels, growth retardation, and impaired skeletal acquisition. To investigate whether hormonal replacement therapy would improve the skeletal phenotype in cases of Igfals gene ablation, we treated male ALSKO mice with GH, IGF-I, or a combination of both. Treatments were administered to animals between 4 and 16 weeks of age or from 8 to 16 weeks of age. Although all treatment groups showed an increase (20%) in serum IGF-I levels, there was no increase in body weight, weight gain, or bone length in either age group. Despite the blunted linear growth in response to hormone therapy, ALSKO mice treated with GH showed radial bone growth, which contributed to bone strength tested by 4-point bending. We found that ALSKO mice treated with GH showed increased total cross-sectional area, cortical bone area, and cortical thickness by microtomography. Dynamic histomorphometry showed that although GH and double treatment groups resulted in trends towards increased bone formation parameters, these did not reach significance. However, bone resorption parameters were significantly increased in all treatment groups. ALSKO mice treated between 4 and 16 weeks of age showed minor differences in bone traits compared with vehicle-treated mice. In conclusion, treatment with GH and IGF-I do not work synergistically to rescue the stunted growth found in mice lacking the Igfals gene. Although GH alone appears to increase bone parameters slightly, it does not affect body weight or linear growth. PMID:24424061

  14. Skeletal response of male mice to anabolic hormone therapy in the absence of the Igfals gene.

    PubMed

    Kennedy, Oran D; Sun, Hui; Wu, Yingjie; Courtland, Hayden-William; Williams, Garry A; Cardoso, Luis; Basta-Pljakic, Jelena; Schaffler, Mitchell B; Yakar, Shoshana

    2014-03-01

    IGF-I is a critical regulator of skeletal acquisition, which acts in endocrine and autocrine/paracrine modes. In serum, IGF-I is carried by the IGF-binding proteins in binary complexes. Further stabilization of these complexes is achieved by binding to the acid labile subunit (ALS) in a ternary complex (of IGF-I-IGF-binding protein 3/5-ALS). Ablation of the Igfals gene in humans (ALS deficiency) and mice (ALS knockout [ALSKO]) leads to markedly decreased serum IGF-I levels, growth retardation, and impaired skeletal acquisition. To investigate whether hormonal replacement therapy would improve the skeletal phenotype in cases of Igfals gene ablation, we treated male ALSKO mice with GH, IGF-I, or a combination of both. Treatments were administered to animals between 4 and 16 weeks of age or from 8 to 16 weeks of age. Although all treatment groups showed an increase (20%) in serum IGF-I levels, there was no increase in body weight, weight gain, or bone length in either age group. Despite the blunted linear growth in response to hormone therapy, ALSKO mice treated with GH showed radial bone growth, which contributed to bone strength tested by 4-point bending. We found that ALSKO mice treated with GH showed increased total cross-sectional area, cortical bone area, and cortical thickness by microtomography. Dynamic histomorphometry showed that although GH and double treatment groups resulted in trends towards increased bone formation parameters, these did not reach significance. However, bone resorption parameters were significantly increased in all treatment groups. ALSKO mice treated between 4 and 16 weeks of age showed minor differences in bone traits compared with vehicle-treated mice. In conclusion, treatment with GH and IGF-I do not work synergistically to rescue the stunted growth found in mice lacking the Igfals gene. Although GH alone appears to increase bone parameters slightly, it does not affect body weight or linear growth.

  15. Anabolic steroids.

    PubMed

    Snow, D H

    1993-12-01

    Anabolic steroids have been employed extensively in equine practice over the past 25 years. Their usefulness is largely dependent on subjective opinions, as only minimal studies have been carried out in horses. Therefore, their use will vary markedly between practitioners depending on their personal experiences and pressures by trainers to use them. They form part of rational therapy in a variety of conditions. In addition to use for increasing muscle mass, they are used to a varying extent in the raising of yearlings and in the training and racing of horses with the view of improving performance. However, in almost all countries, the latter use is largely curtailed, and the presence of these substances in postrace urine samples constitutes use of an illegal substance. To detect the use of anabolic steroids, including testosterone, sensitive ELISA tests for screening and GC/MS for confirmation have been developed. These compounds can be used safely. Risks can be encountered if too high doses are used, as horses may become difficult to manage due to increased aggressiveness and other stallion-like behavior. Reproductive efficiency in both stallions and mares may be temporarily impaired, but this is quite rapidly reversible following cessation of treatment.

  16. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men

    PubMed Central

    West, Daniel W D; Kujbida, Gregory W; Moore, Daniel R; Atherton, Philip; Burd, Nicholas A; Padzik, Jan P; De Lisio, Michael; Tang, Jason E; Parise, Gianni; Rennie, Michael J; Baker, Steven K; Phillips, Stuart M

    2009-01-01

    We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 ± 1.1 years, BMI = 26 ± 3.5 kg m−2) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF-1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 ± 0.007, LH = 0.071 ± 0.008, HH = 0.064 ± 0.014% h−1; P < 0.05) with no effect of elevated hormones (P= 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post-exercise (P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS. PMID:19736298

  17. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors

    PubMed Central

    West, Daniel W. D.; Burd, Nicholas A.; Tang, Jason E.; Moore, Daniel R.; Staples, Aaron W.; Holwerda, Andrew M.; Baker, Steven K.

    2010-01-01

    The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 ± 1.2 yr, body mass index = 23.1 ± 0.6 kg/m2) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition × training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men. PMID:19910330

  18. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors.

    PubMed

    West, Daniel W D; Burd, Nicholas A; Tang, Jason E; Moore, Daniel R; Staples, Aaron W; Holwerda, Andrew M; Baker, Steven K; Phillips, Stuart M

    2010-01-01

    The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 +/- 1.2 yr, body mass index = 23.1 +/- 0.6 kg/m(2)) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition x training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men.

  19. Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring nutritional rehabilitation.

    PubMed Central

    Byrne, T A; Morrissey, T B; Gatzen, C; Benfell, K; Nattakom, T V; Scheltinga, M R; LeBoff, M S; Ziegler, T R; Wilmore, D W

    1993-01-01

    OBJECTIVE: The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the composition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy. SUMMARY BACKGROUND DATA: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein. METHODS: Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n = 4) or, in addition, received GH 0.14 mg/kg/day (n = 10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and nonmineral-containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition. RESULTS: The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311 +/- 0.6 kg vs. 1.988 +/- 0.2 kg, p < or = 0.03) and more protein (1.417 +/- 0.3 kg vs. 0.086 +/- 0.1 kg, p < or = 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004 +/- 0.3 kg vs. 0.129 +/- 0.2 kg, p < 0

  20. Investigations into the feasibility of routine ultra high performance liquid chromatography-tandem mass spectrometry analysis of equine hair samples for detecting the misuse of anabolic steroids, anabolic steroid esters and related compounds.

    PubMed

    Gray, Bobby P; Viljanto, Marjaana; Bright, Jane; Pearce, Clive; Maynard, Steve

    2013-07-17

    The detection of the abuse of anabolic steroids in equine sport is complicated by the endogenous nature of some of the abused steroids, such as testosterone and nandrolone. These steroids are commonly administered as intramuscular injections of esterified forms of the steroid, which prolongs their effects and improves bioavailability over oral dosing. The successful detection of an intact anabolic steroid ester therefore provides unequivocal proof of an illegal administration, as esterified forms are not found endogenously. Detection of intact anabolic steroid esters is possible in plasma samples but not, to date, in the traditional doping control matrix of urine. The analysis of equine mane hair for the detection of anabolic steroid esters has the potential to greatly extend the time period over which detection of abuse can be monitored. Equine mane hair samples were incubated in 0.1M phosphate buffer (pH 9.5) before anabolic steroids (testosterone, nandrolone, boldenone, trenbolone and stanozolol), anabolic steroid esters (esters of testosterone, nandrolone, boldenone and trenbolone) and associated compounds (fluticasone propionate and esters of hydroxyprogesterone) were extracted by liquid-liquid extraction with a mix of hexane and ethyl acetate (7:3, v:v). Further sample clean up by solid phase extraction was followed by derivatisation with methoxylamine HCL and analysis by UHPLC-MS/MS. Initial method development was performed on a representative suite of four testosterone esters (propionate, phenylpropionate, isocaproate and decanoate) and the method was later extended to include a further 18 compounds. The applicability of the method was demonstrated by the analysis of mane hair samples collected following the intramuscular administration of 500 mg of Durateston(®) (mixed testosterone esters) to a Thoroughbred mare (560 kg). The method was subsequently used to successfully detect boldenone undecylenate and stanozolol in hair samples collected following

  1. Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH.

    PubMed

    Saini, Vaibhav; Marengi, Dean A; Barry, Kevin J; Fulzele, Keertik S; Heiden, Erica; Liu, Xiaolong; Dedic, Christopher; Maeda, Akira; Lotinun, Sutada; Baron, Roland; Pajevic, Paola Divieti

    2013-07-12

    Parathyroid hormone (PTH) is the only Food and Drug Administration-approved anabolic agent to treat osteoporosis; however, the cellular targets of PTH action in bone remain controversial. PTH modulates bone turnover by binding to the PTH/PTH-related peptide (PTHrP) type 1 receptor (PPR), a G-protein-coupled receptor highly expressed in bone and kidneys. Osteocytes, the most abundant cells in adult bone, also express PPR. However, the physiological relevance of PPR signaling in osteocytes remains to be elucidated. Toward this goal, we generated mice with PPR deletion in osteocytes (Ocy-PPRKO). Skeletal analysis of these mice revealed a significant increase in bone mineral density and trabecular and cortical bone parameters. Osteoblast activities were reduced in these animals, as demonstrated by decreased collagen type I α1 mRNA and receptor activator of NF-κB ligand (RANKL) expression. Importantly, when subjected to an anabolic or catabolic PTH regimen, Ocy-PPRKO animals demonstrated blunted skeletal responses. PTH failed to suppress SOST/Sclerostin or induce RANKL expression in Ocy-PPRKO animals compared with controls. In vitro, osteoclastogenesis was significantly impaired in Ocy-PPRKO upon PTH administration, indicating that osteocytes control osteoclast formation through a PPR-mediated mechanism. Taken together, these data indicate that PPR signaling in osteocytes is required for bone remodeling, and receptor signaling in osteocytes is needed for anabolic and catabolic skeletal responses.

  2. Parathyroid Hormone (PTH)/PTH-related Peptide Type 1 Receptor (PPR) Signaling in Osteocytes Regulates Anabolic and Catabolic Skeletal Responses to PTH*

    PubMed Central

    Saini, Vaibhav; Marengi, Dean A.; Barry, Kevin J.; Fulzele, Keertik S.; Heiden, Erica; Liu, Xiaolong; Dedic, Christopher; Maeda, Akira; Lotinun, Sutada; Baron, Roland; Pajevic, Paola Divieti

    2013-01-01

    Parathyroid hormone (PTH) is the only Food and Drug Administration-approved anabolic agent to treat osteoporosis; however, the cellular targets of PTH action in bone remain controversial. PTH modulates bone turnover by binding to the PTH/PTH-related peptide (PTHrP) type 1 receptor (PPR), a G-protein-coupled receptor highly expressed in bone and kidneys. Osteocytes, the most abundant cells in adult bone, also express PPR. However, the physiological relevance of PPR signaling in osteocytes remains to be elucidated. Toward this goal, we generated mice with PPR deletion in osteocytes (Ocy-PPRKO). Skeletal analysis of these mice revealed a significant increase in bone mineral density and trabecular and cortical bone parameters. Osteoblast activities were reduced in these animals, as demonstrated by decreased collagen type I α1 mRNA and receptor activator of NF-κB ligand (RANKL) expression. Importantly, when subjected to an anabolic or catabolic PTH regimen, Ocy-PPRKO animals demonstrated blunted skeletal responses. PTH failed to suppress SOST/Sclerostin or induce RANKL expression in Ocy-PPRKO animals compared with controls. In vitro, osteoclastogenesis was significantly impaired in Ocy-PPRKO upon PTH administration, indicating that osteocytes control osteoclast formation through a PPR-mediated mechanism. Taken together, these data indicate that PPR signaling in osteocytes is required for bone remodeling, and receptor signaling in osteocytes is needed for anabolic and catabolic skeletal responses. PMID:23729679

  3. [The reaction of hormones of hypophysis-thyroid gland's endocrinal axis on vibration pathology and on condition of it's correction with liquid oxygen and anabolic steroids].

    PubMed

    Abzianidze, E N

    2007-06-01

    The experiment was held on white male rats. After the tests had been finished, by means of immunofermental method the concentration of thyroid (T3 and T4) and thyrotrophic (TSH) hormones were defined in the blood of animals in condition of vibropathology and it's correction with liquid oxygen and retabolil. The research showed, that the level of TSH, T3 and T4 decreased in condition of vibropathology and it's correction with anabolic steroid compare with control groups. But against of background liquid oxygen's injection the level of TSH increased, but the concentration of T3 and T4 were reduced compare with control group, though they were increased compare with the rest groups of experimental animals. As a result of the search, it was established, that the impact of vibration on the organism of male rats causes important changes in the hypophysis-thyroid gland's endocrinal axis, particularly it takes place the hypofunction of thyroid gland. And it's worth to mention that the correction of vibropathology with liquid oxygen cause positive influence and changes in the organism. There is a positively expressed normalization of thyroid and thyrotrophic hormones' concentration, but the correction of vibropathology with anabolic steroid has not been a successful one.

  4. Anabolic steroids.

    PubMed

    Kuhn, Cynthia M

    2002-01-01

    The term "anabolic steroids" refers to testosterone derivatives that are used either clinically or by athletes for their anabolic properties. However, scientists have questioned the anabolic effects of testosterone and its derivatives in normal men for decades. Most scientists concluded that anabolic steroids do not increase muscle size or strength in people with normal gonadal function and have discounted positive results as unduly influenced by positive expectations of athletes, inferior experimental design, or poor data analysis. There has been a tremendous disconnect between the conviction of athletes that these drugs are effective and the conviction of scientists that they aren't. In part, this disconnect results from the completely different dose regimens used by scientists to document the correction of deficiency states and by athletes striving to optimize athletic performance. Recently, careful scientific study of suprapharmacologic doses in clinical settings - including aging, human immunodeficiency virus, and other disease states - supports the efficacy of these regimens. However, the mechanism by which these doses act remains unclear. "Anabolism" is defined as any state in which nitrogen is differentially retained in lean body mass, either through stimulation of protein synthesis and/or decreased breakdown of protein anywhere in the body. Testosterone, the main gonadal steroid in males, has marked anabolic effects in addition to its effects on reproduction that are easily observed in developing boys and when hypogonadal men receive testosterone as replacement therapy. However, its efficacy in normal men, as during its use in athletes or in clinical situations in which men are eugonadal, has been debated. A growing literature suggests that use of suprapharmacologic doses can, indeed, be anabolic in certain situations; however, the clear identification of these situations and the mechanism by which anabolic effects occur are unclear. Furthermore, the

  5. Loss of Gsα in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy*

    PubMed Central

    Sinha, Partha; Aarnisalo, Piia; Chubb, Rhiannon; Poulton, Ingrid J.; Guo, Jun; Nachtrab, Gregory; Kimura, Takaharu; Swami, Srilatha; Saeed, Hamid; Chen, Min; Weinstein, Lee S.; Schipani, Ernestina; Sims, Natalie A.; Kronenberg, Henry M.; Wu, Joy Y.

    2016-01-01

    Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-GsαOsxKO mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1–34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-GsαOsxKO mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-GsαOsxKO mice. In mice that express a mutated PTH1R that activates adenylyl cyclase and protein kinase A (PKA) via Gsα but not phospholipase C via Gq/11 (D/D mice), PTH significantly enhanced bone formation, indicating that phospholipase C activation is not required for increased bone turnover in response to PTH. Therefore, although the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of Gsα in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond Gsα and Gq/11 act downstream of PTH on osteoblast differentiation. PMID:26598522

  6. [Heterologous expression of functionally active human cytochrome P-450s. Cytochrome P-450IIIA4 catalyzes the biotransformation of the anabolic steroid hormone methandrostenolone].

    PubMed

    Krynetskiĭ, E Iu; Kovaleva, I E; Luzikov, V N

    1994-02-01

    The expression of the cytochrome P450IIIA4 gene in the Saccharomyces cerevisiae yeast using the shuttle vector pYeDP1-8/2 has been carried out. The microsomal fraction isolated from the transformed yeast cells was used for biotransformation of the anabolic steroid hormone-methandrostenolone (MA). The microsomal oxidation products were analyzed by HPLC and two-dimensional TLC. It was shown that microsomes of the yeasts expressing human cytochrome P450IIIA4 catalyze the MA conversion into its 6 beta-hydroxy derivative. An identical product is formed via a reaction catalyzed by human liver microsomes. The use of the heterological system of cytochrome P450IIIA4 expression has made it possible to establish its role in MA metabolism. The experimental system simulates the first phase of the drug biotransformation in liver cells.

  7. The Relationships between Anabolic Hormones and Body Composition in Middle-Aged and Elderly Men with Prediabetes: A Cross-Sectional Study

    PubMed Central

    Rabijewski, Michał; Papierska, Lucyna; Piątkiewicz, Paweł

    2016-01-01

    The influence of anabolic hormones and body composition in men with prediabetes (PD) is unknown. In a cross-sectional study we investigated the relationships between total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) and body composition assessed using dual-energy X-ray absorptiometry (DXA) method in 84 patients with PD (40–80 years) and 56 men in control group. Patients with PD had lower TT, cFT, and DHEAS levels but similar IGF-1 levels in both groups. Patients with PD presented the higher total and abdominal fat as well as the lower total and abdominal lean than control (p < 0.02, p < 0.01, p < 0.05, and p < 0.02, resp.). We observed negative relationship between TT and total fat (p = 0.014) and positive with abdominal lean mass (p = 0.034), while cFT was negatively associated with abdominal (p = 0.02), trunk (p = 0.024), and leg fat (p = 0.037) and positively associated with total (p = 0.022) and trunk lean (p = 0.024). DHEAS were negatively associated with total fat (p = 0.045), and IGF-1 were positively associated with abdominal (p = 0.003) and leg lean (p = 0.015). In conclusion, the lowered anabolic hormones are involved in body composition rearrangement in men with PD. Further studies are needed to establish whether the androgen replacement therapy would be beneficial in men with PD. PMID:27274996

  8. Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

    PubMed

    Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao

    2017-09-15

    Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC50) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Effect of low-intensity resistance training with heat stress on the HSP72, anabolic hormones, muscle size, and strength in elderly women.

    PubMed

    Yoon, Sung Jin; Lee, Moon Jin; Lee, Hyo Min; Lee, Jin Seok

    2016-11-19

    Several recent studies have reported that heat stress stimulates the activation of heat shock protein 72 (HSP72), leading to an increase in muscle synthesis. Some studies suggested that low-intensity resistance training combined with heat stress could improve muscle size and strength. This study aimed to identify the effect of low-intensity resistance training with heat stress over 12 weeks on the HSP72, anabolic hormones, muscle size, and strength in elderly women. The subjects were physically healthy women of 65-75 years, who were randomly assigned to one of three groups: a low-intensity resistance training with heating sheet group (HRT group, n = 8), a moderate-intensity resistance training (RT group, n = 6), and a heating sheet group (HEAT group, n = 7). Computed tomography scans, 1-repetition maximum (1RM), and blood samples were taken pre- and post-training. The HSP72 did not vary significantly between the different groups and times. The IGF-1 and 1RM had significantly increased in all three groups after the training (respectively, p < 0.05). Moreover, the cross-sectional area (CSA) of the quadriceps showed a significantly greater increase in the HRT group than in the HEAT group (p < 0.05). We found that low-intensity training with heat stress stimulated the anabolic hormones of elderly women, improving their muscle strength and hypertrophy. We believe that low-intensity training with heat stress is an effective way to prevent muscle atrophy and to improve muscle strength in elderly women.

  10. Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice.

    PubMed

    Gray, Sarah K; McGee-Lawrence, Meghan E; Sanders, Jennifer L; Condon, Keith W; Tsai, Chung-Jui; Donahue, Seth W

    2012-09-01

    Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has deleterious consequences in muscle and bone, leading to decreased mobility, progressive osteoporosis, and premature death. Patients with DMD experience a higher-than-average fracture rate, particularly in the proximal and distal femur and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid hormone, an effective anabolic agent for post-menopausal and glucocorticoid-induced osteoporosis, has not been explored for DMD. Black bear parathyroid hormone (bbPTH) has been implicated in the maintenance of bone properties during extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid residue differences from human PTH. Apoptosis was mitigated and cAMP was activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1-84 to 4-week old male mdx and wild type mice via daily (5×/week) subcutaneous injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone volume fraction than wild type mice. No changes were found in femoral cortical bone geometry or mechanical properties with bbPTH treatment in wild type mice, and only medio-lateral moment of inertia changed with bbPTH treatment in mdx femurs. However, μCT analyses of the trabecular regions of the distal femur and proximal tibia showed marked increases in bone volume fraction with bbPTH treatment, with a greater anabolic response (7-fold increase) in mdx mice than wild type mice (2-fold increase). Trabecular number increased in mdx long bone, but not wild type bone. Additionally, greater osteoblast area and decreased osteoclast area were observed with bbPTH treatment in mdx mice. The heightened response to PTH in mdx bone compared to wild type suggests a link between dystrophin deficiency, altered calcium signaling, and bone. These findings support further investigation of PTH as an anabolic

  11. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the Administrator...

  12. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  13. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  14. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  15. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  16. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by μCT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  17. The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB/c mice.

    PubMed

    Gohin, S; Carriero, A; Chenu, C; Pitsillides, A A; Arnett, T R; Marenzana, M

    2016-03-01

    There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L-NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1-34] (80 µg/kg/day) or L-NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro-CT, histomorphometry and three-point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co-treatment with L-NAME blocked the action of PTH on blood flow, whereas L-NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co-treatment with L-NAME restricted the PTH-stimulated increase in cortical bone formation but had no clear-cut effects in trabecular bone. Co-treatment with L-NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO-mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone.

  18. Nmp4/CIZ suppresses the response of bone to anabolic parathyroid hormone by regulating both osteoblasts and osteoclasts

    PubMed Central

    Childress, Paul; Philip, Binu K.; Robling, Alexander G.; Bruzzaniti, Angela; Kacena, Melissa A.; Bivi, Nicoletta; Plotkin, Lilian I.; Heller, Aaron; Bidwell, Joseph P.

    2011-01-01

    How parathyroid hormone (PTH) increases bone mass is unclear but understanding this phenomenon is significant to the improvement of osteoporosis therapy. Nmp4/CIZ is a nucleocytoplasmic shuttling transcriptional repressor that suppresses PTH-induced osteoblast gene expression and hormone-stimulated gains in murine femoral trabecular bone. To further characterize Nmp4/CIZ suppression of hormone-mediated bone growth we treated 10 wk-old Nmp4-knockout (KO) and wild-type (WT) mice with intermittent human PTH (1-34) at 30μg/kg/day or vehicle, 7 days/wk, for 2, 3, or 7 wks. Null mice treated with hormone (7 wks) gained more vertebral and tibial cancellous bone than WT animals paralleling the exaggerated response in the femur. Interestingly, Nmp4/CIZ suppression of this hormone-stimulated bone formation was not apparent during the first 2 wks of treatment. Consistent with the null mice enhanced PTH-stimulated addition of trabecular bone these animals exhibited an augmented hormone-induced increase in serum osteocalcin 3 wks into treatment. Unexpectedly the Nmp4-KO mice displayed an osteoclast phenotype. Serum C-terminal telopeptides, a marker for bone resorption, was elevated in the null mice, irrespective of treatment. Nmp4-KO bone marrow cultures produced more osteoclasts, which exhibited an elevated resorbing activity, compared to WT cultures. The expression of several genes critical to the development of both osteoblasts and osteoclasts were elevated in Nmp4-KO mice at 2 wks but not 3 wks of hormone exposure. We propose that Nmp4/CIZ dampens PTH-induced improvement of trabecular bone throughout the skeleton by transiently suppressing hormone-stimulated increases in the expression of proteins key to the required enhanced activity/number of both osteoblasts and osteoclasts. PMID:21607813

  19. A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.

    PubMed

    Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Suda, Hirofumi; Miyata, Shigeru; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert C

    2012-09-01

    Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1-33) to a collagen binding domain (PTH-CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH-CBD (320 μg/kg). PTH-CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH-CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH-CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH-CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH-CBD caused sustained increases in BMD by >10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy.

  20. Weight loss and low body cell mass in males with lung cancer: relationship with systemic inflammation, acute-phase response, resting energy expenditure, and catabolic and anabolic hormones.

    PubMed

    Simons, J P; Schols, A M; Buurman, W A; Wouters, E F

    1999-08-01

    The aim of the present study was to investigate, in human lung cancer, the relationship between weight loss and the existence of a low body cell mass (BCM) on the one hand, and the putative presence of systemic inflammation, an increased acute-phase response, anorexia, hypermetabolism and changes in circulating levels of several anabolic and catabolic hormones on the other. In 20 male lung cancer patients, pre-stratified by weight loss of >/=10% (n=10) or of <10% (n=10), the following measurements were performed: BCM (by dual-energy X-ray absorptiometry/bromide dilution), circulating levels of sTNF-R55 and sTNF-R75 (soluble tumour necrosis factor receptors of molecular masses 55 and 75 kDa respectively), interleukin-6, lipopolysaccharide-binding protein, albumin, appetite (scale of 0-10), resting energy expenditure (by indirect calorimetry) and circulating levels of catabolic (cortisol) and anabolic [testosterone, insulin-like growth factor-I (IGF-I)] hormones. Compared with the patients with a weight loss of <10%, those with a weight loss of >/=10% were characterized by higher levels of sTNF-R55 (trend towards significance; P=0.06), and lower levels of albumin (27.4 compared with 34.4 mmol/l; P=0.02), testosterone (13.2 compared with 21.5 nmol/l; P=0.01) and IGF-I (119 compared with 184 ng/ml; P=0.004). In the patient group as a whole, the percentage weight loss was significantly correlated with sTNF-R55 (r=0.59, P=0.02), albumin (r=-0.63, P=0.006) and IGF-I (r=-0.50, P=0.02) levels. Height-adjusted BCM was significantly correlated with sTNF-R55 (r=-0.57, P=0.03), sTNF-R75 (r=-0.50, P=0. 04), lipopolysaccharide-binding protein (r=-0.50, P=0.04), albumin (r=0.56, P=0.02) and resting energy expenditure/BCM (r=-0.54, P=0. 03), and there was a trend towards a correlation with IGF-I concentration (r=0.44, P=0.06). We conclude that, in human lung cancer, weight loss and the presence of a low BCM are associated with systemic inflammation, an increased acute

  1. Steroid hormone activity of flavonoids and related compounds.

    PubMed

    Zand, R S; Jenkins, D J; Diamandis, E P

    2000-07-01

    Soy isoflavones have been studied extensively for estrogenic and antiestrogenic properties. Other flavonoids, found in fruits, vegetables, tea and wine, have been much less tested for steroid hormone activity. We therefore assessed the estrogenic, androgenic and progestational activities of 72 flavonoids and structurally-related compounds. These compounds were tested on BT-474 human breast cancer cells at concentrations of 10(8)-10(-5) M, with estradiol (estrogen), norgestrel (progestin) and dihydrotestosterone (androgen) used as positive controls, and ethanol (solvent) as a negative control. pS2, an estrogen-regulated protein, and prostate-specific antigen (PSA), regulated by androgens and progestins, were quantified in tissue culture supernatants using ELISA-type immunofluorometric assays developed in-house. Of the 72 compounds tested, 18 showed estrogenic activity at 10(-5) M. Of this subset, seven also showed progestational activity at this concentration. The soy isoflavones, biochanin A and genistein, showed the most potent estrogenic activity, with a dose-response effect up to 10(-7) M. Of all other flavonoids, luteolin and naringenin displayed the strongest estrogenicity, while apigenin had a relatively strong progestational activity. Based on our data, we have formulated a set of structure/function relationships between the tested compounds. Flavonoids, therefore, exhibit significant steroid hormone activity, and may have an effect in the modification of cancer risk by diet, or in cancer therapeutics and prevention.

  2. Miscellaneous uses of anabolic steroids.

    PubMed

    Kopera, H

    1993-01-01

    The original list of indications for anabolic-androgenic steroids has been reduced to those discussed in this publication so far and to mammary carcinoma, deficiency states and growth disorders. In disseminated endocrine-responsive mammary carcinoma in the female, anabolic drugs have a proven palliative effect in some 20 to 40% of patients, arresting tumour growth for up to 12 months and improving the patient's general condition. In high doses they can cause a disturbing increase in libido. Patients with deficiency states can, irrespective of the cause, benefit from adjunctive anabolic steroid treatment, provided their food supply is adequate. Positive effects are exerted by the anabolic agents' protein anabolic and anticatabolic actions, by psychic stimulation of the patient and by enhancement of recovery. Current trials strongly indicate that oral anabolic drugs administered alone or in combination with growth hormone or thyroid preparations are of therapeutic value in growth disorders such as constitutional delay of growth and puberty, hypopituitary dwarfism, chronic renal diseases and in Turner's syndrome.

  3. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone

    PubMed Central

    Pacifici, Roberto

    2015-01-01

    Osteoimmunology is field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciothropic hormones are bone marrow T lymphocytes. T cells secrete osteoclastogenic cytokines such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b. In addition, T cells regulate the differentiation and life span of stromal cells and their responsiveness to parathyroid hormone (PTH) via costimulatory molecules expressed on their surface. The conditioning effect of T cells on stromal cells (SCs) is inherited by the osteoblastic and osteocytic progeny of SCs. As a result, osteoblastic cells of T cell–deficient mice have functional characteristics different from corresponding cells of T cell–replete mice. These differences include the ratio of RANKL/OPG produced in response to continuous PTH treatment, and the osteoblastogenic response to intermittent PTH treatment. This article reviews the evidence indicating that the effects of parathyroid hormone are mediated not only by osteoblasts and osteocytes but also by T cells. PMID:26662934

  4. Anabolic steroid boosts weight.

    PubMed

    1996-09-01

    A randomized study of nandrolone decanoate (Deca-Durabolin) showed that the anabolic steroid can increase weight in people with HIV infections. The group receiving nandrolone experienced a greater increase both in fat-free mass and body cell mass (although the latter measure did not reach statistical significance) than those on placebo. Deca-Durabolin had little to do with two occurrences of Kaposi's sarcoma (KS) in the study group, but until further studies are completed, caution is advised when using this steroid in patients with KS. A new study comparing nandrolone to growth hormone in patients with wasting is slated to begin in the next 3 or 4 months.

  5. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone.

    PubMed

    Pacifici, Roberto

    2016-01-01

    Osteoimmunology is a field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciothropic hormones are bone marrow T lymphocytes. T cells secrete osteoclastogenic cytokines such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b. In addition, T cells regulate the differentiation and life span of stromal cells (SCs) and their responsiveness to parathyroid hormone (PTH) via costimulatory molecules expressed on their surface. The conditioning effect of T cells on SCs is inherited by the osteoblastic and osteocytic progeny of SCs. As a result, osteoblastic cells of T cell-deficient mice have functional characteristics different from corresponding cells of T cell-replete mice. These differences include the ratio of RANKL/OPG produced in response to continuous PTH treatment, and the osteoblastogenic response to intermittent PTH treatment. This article reviews the evidence indicating that the effects of PTH are mediated not only by osteoblasts and osteocytes but also by T cells.

  6. The standardization of nonsterile compounding: a study in quality control and assessment for hormone compounding.

    PubMed

    Wiley, T S; Odegard, R D; Raden, J; Haraldsen, J T

    2014-01-01

    Sterile and nonsterile compounding of medication has attracted much attention over the last few years due to the onset of various infections and negative compounding practices. This paper reports on the standardization of compounded hormones utilizing the Wiley Protocol, which provides nonsynthetic bioidentical estradiol, progesterone, dehydroepiandrosterone, and testosterone in a transdermal topical cream base for women and men in a standardized dosing regimen. Here, we present data from 2008 through 2012, which details the process of standardization and quality testing of the hormones through submission of random compounded samples for quality control and assessment. Pharmacies delivering the Wiley Protocol were required to follow the same compounding formulation, as well as submit random samples for quarterly testing. Sample concentrations were tested using high-performance liquid chromatography. We found that pharmacies that submitted samples had a 91% passing rating with a percent of target of 98.6% +/- 8.4%. It was also determined that pharmacies that prepared more compounded cream had a higher passing rating than those that prepared limited quantities. We found that standardization across multiple pharmacies could be achieved through quarterly testing of submitted samples by a third-party laboratory when following necessary procedures as defined by the Wiley Protocol. It was also determined that experience and training were a critical factor in the mixing of compounded prescriptions, with high consistency and accuracy providing patient safety.

  7. Effects of a daily mixed nutritional supplement on physical performance, body composition, and circulating anabolic hormones during 8 weeks of arduous military training.

    PubMed

    Fortes, Matthew B; Diment, Bethany C; Greeves, Julie P; Casey, Anna; Izard, Rachel; Walsh, Neil P

    2011-12-01

    The aim of this work was to investigate the effect of a daily mixed nutritional supplement upon body composition, physical performance, and circulating anabolic hormones in soldiers undergoing arduous training. Thirty males received either a habitual diet alone (CON, n = 15) or with the addition of a daily mixed supplement (SUP, n = 15) of ∼5.1 MJ·d⁻¹ during 8 weeks of training. Body composition (DEXA), maximal dynamic lift strength (MDLS), and vertical jump (VJ) were assessed, and resting blood samples were collected before and after training. Blood analysis included insulin-like growth factors (IGF-1, IGF BP-1, and IGF BP-3), testosterone, and cortisol. There were no group differences at baseline. Body mass loss (mean ± SD) (CON 5.0 ± 2.3, SUP 1.6 ± 1.5 kg), lean mass loss (CON 2.0 ± 1.5, SUP 0.7 ± 1.5 kg), and fat mass loss (CON 3.0 ± 1.6, SUP 0.9 ± 1.8 kg) were significantly blunted by SUP. CON experienced significant decrements in MDLS (14%), VJ (10%), and explosive leg power (11%) that were prevented by SUP. Military training significantly reduced circulating IGF-1 (28%), testosterone (19%), and the testosterone:cortisol ratio (24%) with no effect of SUP. Circulating IGF BP-1 concentration and cortisol remained unchanged throughout, although SUP abolished the significant decrease in circulating IGF BP-3 (20%) on CON. In conclusion, a daily mixed nutritional supplement attenuated decreases in body mass and lean mass and prevented the decrease in physical performance during an arduous military training program.

  8. Anabolic steroids.

    PubMed

    Brower, K J

    1993-03-01

    Anabolic-androgenic steroids are controlled substances that are taken illicitly to enhance physical appearance and performance. In addition to the desired somatic effects, reasonably good evidence suggests that AASs are capable of influencing mood and behavior. A myriad of adverse effects have been reported. Although many of these effects appear to reverse with cessation of use, fatalities due to suicides, homicides, liver disease, heart attacks, and cancer have been reported infrequently among illicit users. Although studies are needed to quantify more precisely the long-term consequences and risks of using AASs, patterns of illicit use are particularly troublesome. The use of extremely high doses, needles, counterfeit and veterinary drugs, and multiple steroidal and nonsteroidal drugs simultaneously may further enhance the risks of using AASs. The clinician should suspect AAS use in high-risk individuals who manifest any of the possible consequences described in this article. Laboratory tests can be valuable for detection of use and assessment of consequences. Treatment approaches may borrow from proven techniques employed with other substance abusers, but should also address the special value that physical attributes and body image have for the AAS user.

  9. Emerging anabolic treatments in osteoporosis.

    PubMed

    Mosekilde, Leif; Tørring, Ove; Rejnmark, Lars

    2011-04-01

    Anabolic treatment that remodels bone tissue and restores bone biomechanical competence is essential in the treatment of osteoporosis. In addition, long term antiresorptive therapy may have limitations because of the reduced renewal of bone tissue. The only pure anabolic drugs available at present are intact PTH (1-84) (Preotact®) and the truncated PTH (1-34) (Teriparatide, Forteo®) while strontium ranelate may possess antiresorptive as well as anabolic properties. The marketed antiresorptive and anabolic antiosteoporotic drugs have limitations in their use due to adverse effects or to the occurrence of rare but severe late complications. Furthermore, indications may be restricted by co-existing diseases or treatment duration may be limited. However, new anabolic drugs are being developed mimicking the effect of PTH, or targeting the calcium sensing receptor (CaSR) or the Wnt/β-catenin signalling pathway. The PTH mimetics are truncated or altered PTH fragments, parathyroid hormone related peptide (PTHrP) and calcilytics stimulating endogenous PTH secretion. Calcimimetics (e.g. strontium) and calcilytics (e.g. lithium) may also affect bone cells directly through the CaSR. The Wnt pathway that stimulates osteoblastic proliferation, differentiation and function may be activated by neutralizing antibodies to secreted inhibitors of Wnt signalling (e.g. Sclerostin or Dickkopf) or by small molecules (e.g. lithium) that inhibits the glycogen synthase kinase 3β mediated degradation of β-catenin. Finally, blocking of activin A by soluble receptor fusion proteins has been shown to increase bone mass by a dual anabolic-antiresorptive action. The present paper summarises the physiological background and the present evidence for these effects.

  10. 21 CFR 1308.33 - Exemption of certain anabolic steroid products; application.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exemption of certain anabolic steroid products... SCHEDULES OF CONTROLLED SUBSTANCES Exempt Anabolic Steroid Products § 1308.33 Exemption of certain anabolic... compound, mixture, or preparation containing an anabolic steroid as defined in part 1300 of this chapter...

  11. Anabolic agent use in adults with cystic fibrosis.

    PubMed

    Green, Heather D; Barry, Peter J; Jones, Andrew M

    2015-10-01

    The use of non-prescribed anabolic agents amongst non-athletes is increasing with young, adult males with cystic fibrosis (CF) in the highest risk demographic. There is evidence that anabolic agents increase weight and muscle mass in adults with a variety of catabolic conditions but there is no evidence for their use in hormone sufficient adults with CF. We report a case of anabolic agent use in a male adult with CF and review the clinical features of anabolic agent use with a focus on adults with CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. New anabolic therapies for osteoporosis.

    PubMed

    Minisola, Salvatore; Cipriani, Cristiana; Occhiuto, Marco; Pepe, Jessica

    2017-08-05

    Osteoporosis is characterized by low bone mass and qualitative structural abnormalities of bone tissue, leading to increased bone fragility that results in fractures. Pharmacological therapy is aimed at decreasing the risk of fracture, mainly correcting the imbalance between bone resorption and formation at the level of bone remodeling units. Anabolic therapy has the capability to increase bone mass to a greater extent than traditional antiresorptive agents. The only currently available drug licensed is parathyroid hormone 1-34 (teriparatide); new drugs are on the horizon, targeting the stimulation of bone formation, and therefore improving bone mass, structure and ultimately skeletal strength. These are represented by abaloparatide (a 34-amino acid peptide which incorporates critical N-terminal residues, shared by parathyroid hormone and parathyroid hormone-related protein, followed by sequences unique to the latter protein) and romosozumab (an antibody to sclerostin). In the future, the availability of new anabolic treatment will allow a more extensive utilization of additive and sequential approach, with the goal of both prolonging the period of treatment and, more importantly, avoiding the side effects consequent to long-term use of traditional drugs.

  13. Androgenic-anabolic activities of some new synthesized steroidal pyrane, pyridine and thiopyrimidine derivatives.

    PubMed

    Abdalla, Mohamed M; Amr, Abd El-Galil E; Al-Omar, Mohamed A; Hussain, Azza A; Amer, Mohamed S

    2014-01-01

    In continuation of our previous work, fused steroidal derivatives with pyrane, pyridine, pyrimidine moieties were synthesized and evaluated as androgenic-anabolic agents. Some of the newly synthesized compounds are exhibited pronounced androgenic-anabolic activities.

  14. Mail-Based Intervention for Sarcopenia Prevention Increased Anabolic Hormone and Skeletal Muscle Mass in Community-Dwelling Japanese Older Adults: The INE (Intervention by Nutrition and Exercise) Study.

    PubMed

    Yamada, Minoru; Nishiguchi, Shu; Fukutani, Naoto; Aoyama, Tomoki; Arai, Hidenori

    2015-08-01

    The aim of the Intervention by Nutrition and Exercise (INE) study was to investigate the effects of a mail-based intervention for sarcopenia prevention on muscle mass and anabolic hormones in community-dwelling older adults. A cluster-randomized controlled trial. This trial recruited community-dwelling adults aged 65 years and older in Japan. The 227 participants were cluster randomized into a walking and nutrition (W/N) group (n = 79), a walking (W) group (n = 71), and a control (C) group (n = 77). We analyzed the physical and biochemical measurements in this substudy. Six months of mail-based intervention (a pedometer-based walking program and nutritional supplementation). The skeletal muscle mass index (SMI) using the bioelectrical impedance data acquisition system, biochemical measurements, such as those of insulinlike growth factor (IGF-1), dehydroepiandrosterone sulfate (DHEA-S), and 25-hydroxy vitamin D (25[OH]D), as well as frailty, were assessed by the Cardiovascular Health Study criteria. Participants in the W/N and W groups had significantly greater improvements in SMI, IGF-1, and 25(OH)D (P < .05) than those in the C group. Participants in the W/N group had significantly greater improvements in DHEA-S (P < .05) than in the other groups. These effects were more pronounced in frail, older adults. These results suggest that the mail-based walking intervention of the remote monitoring type for sarcopenia prevention can increase anabolic hormone levels and SMI in community-dwelling older adults, particularly in those who are frail. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  15. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women.

    PubMed

    Pinkerton, JoAnn V; Santoro, Nanette

    2015-09-01

    Two surveys (Harris and Rose surveys) were conducted to quantify the use of compounded hormone therapy (CHT; or bioidentical hormone therapy) among perimenopausal and postmenopausal women in the United States, to assess women's knowledge of CHT versus Food and Drug Administration (FDA)-approved hormone therapy, and to gather information on menopausal experience. The Harris survey was administered to 801 women aged 45 to 60 years who had experienced at least one menopausal symptom. The Rose survey was administered to 2,044 women aged 40 years or older who were ever users of hormone therapy. Women were queried about menopausal symptoms, hormone therapy use, and knowledge of CHT. Findings from the Rose survey were extrapolated using US Census Bureau data and prescription claims for FDA-approved hormone therapy to estimate the prevalence of CHT use. According to extrapolations using Rose data, up to 2.5 million US women aged 40 years or older may use CHT annually, accounting for 28% to 68% of hormone therapy prescriptions. Harris data showed that 86% of women surveyed were unaware that CHT products are not FDA-approved. The Rose survey asked a subset of 1,771 women whether their hormone therapy had been personalized based on hormone levels; 21% (378) answered "yes" whereas 27% (476) did not know. In both surveys, most hormone therapy users stated that their physician had recommended the treatment. We estimate that 1 million to 2.5 million US women aged 40 years or older use CHT. The data suggest that many women are unaware that compounded hormones have not been evaluated or approved by the FDA. Providers have an educational opportunity to ensure that women considering hormone therapy understand the risks and benefits of inadequately regulated CHT.

  16. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women

    PubMed Central

    Pinkerton, JoAnn V.; Santoro, Nanette

    2015-01-01

    Abstract Objective: Two surveys (Harris and Rose surveys) were conducted to quantify the use of compounded hormone therapy (CHT; or bioidentical hormone therapy) among perimenopausal and postmenopausal women in the United States, to assess women's knowledge of CHT versus Food and Drug Administration (FDA)–approved hormone therapy, and to gather information on menopausal experience. Methods: The Harris survey was administered to 801 women aged 45 to 60 years who had experienced at least one menopausal symptom. The Rose survey was administered to 2,044 women aged 40 years or older who were ever users of hormone therapy. Women were queried about menopausal symptoms, hormone therapy use, and knowledge of CHT. Findings from the Rose survey were extrapolated using US Census Bureau data and prescription claims for FDA-approved hormone therapy to estimate the prevalence of CHT use. Results: According to extrapolations using Rose data, up to 2.5 million US women aged 40 years or older may use CHT annually, accounting for 28% to 68% of hormone therapy prescriptions. Harris data showed that 86% of women surveyed were unaware that CHT products are not FDA-approved. The Rose survey asked a subset of 1,771 women whether their hormone therapy had been personalized based on hormone levels; 21% (378) answered “yes” whereas 27% (476) did not know. In both surveys, most hormone therapy users stated that their physician had recommended the treatment. Conclusions: We estimate that 1 million to 2.5 million US women aged 40 years or older use CHT. The data suggest that many women are unaware that compounded hormones have not been evaluated or approved by the FDA. Providers have an educational opportunity to ensure that women considering hormone therapy understand the risks and benefits of inadequately regulated CHT. PMID:25692877

  17. Simultaneous determination of anabolic steroids and synthetic hormones in meat by freezing-lipid filtration, solid-phase extraction and gas chromatography-mass spectrometry.

    PubMed

    Seo, Jungju; Kim, Hye-Young; Chung, Bong Chul; Hong, Jongki

    2005-03-04

    Estradiol, testosterone, progesterone, zeranol and diethylstilbestrol including estradiol metabolites were determined simultaneously in meat. Extraction of growth hormones was carried out by ultasonication using a methanol-water mixture. The growth hormones in the meat extract can be effectively separated from lipids by freezing-lipid filtration, followed by C8-solid phase extraction (SPE). During freezing-lipid filtration, about 90% of lipids are removed without any significant loss of growth hormones. For further clean-up, silica- and aminopropyl-SPE were used. To enhance detection sensitivity, the growth hormones are derivatized with trimethylsilyl reagents. Quantitation using isotope-labelled internal standards was performed by gas chromatography-mass spectrometry in the selected ion monitoring mode. The method detection limits were 0.1-0.4 microg/kg for all growth hormones. Overall recoveries of synthetic and natural growth hormones were 68-106% with coefficients of variation of 5-16% for the complete procedure.

  18. [Anabolic/catabolic imbalance in chronic heart failure].

    PubMed

    Cittadini, Antonio; Bossone, Eduardo; Marra, Alberto Maria; Arcopinto, Michele; Bobbio, Emanuele; Longobardi, Salvatore; Cevara, Carmine; Di Michele, Sara; Saccà, Luigi

    2010-06-01

    A metabolic imbalance between anabolic drive and catabolic forces is commonly observed in chronic heart failure (CHF) patients, with the latter prevailing over anabolic hormones. Moreover, anabolic deficiencies are independent markers of poor prognosis. This finding represents a solid background for the implementation of therapeutic trials based on replacement therapy. The somatotropic axis (GH/IGF-1) is the most powerful anabolic axis of the body and its decline is related with a poor outcome and a worse clinical status. Growth hormone (GH) administration may enter the therapeutic arena as adjunctive treatment in patients affected by CHF and GH/IGF-1 deficiency. The T.O.S.CA. project aims at investigating the relationship between CHF and hormonal deficiency.

  19. Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy.

    PubMed

    Kim, Hyun-Yi; Choi, Sehee; Yoon, Ji-Hye; Lim, Hwan Jung; Lee, Hyuk; Choi, Jiwon; Ro, Eun Ji; Heo, Jung-Nyoung; Lee, Weontae; No, Kyoung Tai; Choi, Kang-Yell

    2016-04-01

    Bone anabolic agents promoting bone formation and rebuilding damaged bones would ideally overcome the limitations of anti-resorptive therapy, the current standard prescription for osteoporosis. However, the currently prescribed parathyroid hormone (PTH)-based anabolic drugs present limitations and adverse effects including osteosarcoma during long-term use. Also, the antibody-based anabolic drugs that are currently being developed present the potential limits in clinical application typical of macromolecule drugs. We previously identified that CXXC5 is a negative feedback regulator of the Wnt/β-catenin pathway via its interaction with Dishevelled (Dvl) and suggested the Dvl-CXXC5 interaction as a potential target for anabolic therapy of osteoporosis. Here, we screened small-molecule inhibitors of the Dvl-CXXC5 interaction via a newly established in vitro assay system. The screened compounds were found to activate the Wnt/β-catenin pathway and enhance osteoblast differentiation in primary osteoblasts. The bone anabolic effects of the compounds were shown using ex vivo-cultured calvaria. Nuclear magnetic resonance (NMR) titration analysis confirmed interaction between Dvl PDZ domain and KY-02061, a representative of the screened compounds. Oral administration of KY-02327, one of 55 newly synthesized KY-02061 analogs, successfully rescued bone loss in the ovariectomized (OVX) mouse model. In conclusion, small-molecule inhibitors of the Dvl-CXXC5 interaction that block negative feedback regulation of Wnt/β-catenin signaling are potential candidates for the development of bone anabolic anti-osteoporosis drugs. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  20. Sports-related issues and biochemistry of natural and synthetic anabolic substances.

    PubMed

    Parr, Maria K; Flenker, Ulrich; Schänzer, Wilhelm

    2010-03-01

    Testosterone is the principal male sex hormone. As with all natural steroids, it is biosynthesized from cholesterol. Phase I metabolism employs some very specific enzymes and pathways. Phase II metabolism and excretion follow more general patterns. The effects of testosterone are twofold: anabolic and androgenic. Because of its anabolic effects, testosterone is frequently abused in sports. Because of its endogenous nature, testosterone doping is difficult to detect. The standard procedure is based on the evaluation of the urinary steroid profile. Conspicuous samples then are submitted to compound-specific (13)C/(12)C analysis. Synthetic and endogenous steroids differ in this measure. Numerous xenobiotic compounds have been derived from testosterone. The modifications typically aim at a reduction of the androgenic properties while maintaining the anabolic potential. Most of these compounds have been withdrawn from the legal market. However, they are found to be illicitly added to otherwise inefficient nutritional supplements. These products represent a major problem to doping control. Recently, clinical trials with selective androgen receptor modulators have been started.

  1. Alternatives to animal experimentation for hormonal compounds research.

    PubMed

    Penza, M; Jeremic, M; Montani, C; Unkila, M; Caimi, L; Mazzoleni, G; Di Lorenzo, Diego

    2009-09-01

    Alternatives to animal testing and the identification of reliable methods that may decrease the need for animals are currently the subject of intense investigation worldwide. Alternative testing procedures are particularly important for synthetic and natural chemicals that exert their biological actions through binding nuclear receptors, called nuclear receptors-interacting compounds (NR-ICs), for which research is increasingly emphasizing the limits of several models in the accurate estimation of the physiological consequences of exposure to these compounds. In particular, estrogen receptor interacting compounds (ER-ICs) have a great impact on human health from the therapeutic, nutritional, and toxicological point of view due to the highly permissive nature of the estrogen receptors towards a large number of natural and synthetic compounds. Similar to in vitro systems, recently generated animal models (e.g., animal models generated for the study of estrogen receptor ligands) may fulfill the 3R principles: refine, reduce, and replace. If used correctly, NR-regulated models, such as reporter mice, xenopus, or zebrafish, and models obtained by somatic gene transfer in reporter systems, combined with imaging technologies, may contribute to strongly decreasing the overall number of animals required for NR-IC testing and research. With these models, flexible and highly standardized parameters and reporter marker quantification can be obtained. Here, we highlight the need for the substitution of currently used testing models with more appropriate ones that can reproduce the features and reactivity of specific mammalian target tissue/organs. We consider the promotion of this advancement a research priority bearing scientific, economic, social, and ethical relevance.

  2. Are osteoclasts needed for the bone anabolic response to parathyroid hormone? A study of intermittent parathyroid hormone with denosumab or alendronate in knock-in mice expressing humanized RANKL.

    PubMed

    Pierroz, Dominique D; Bonnet, Nicolas; Baldock, Paul A; Ominsky, Michael S; Stolina, Marina; Kostenuik, Paul J; Ferrari, Serge L

    2010-09-03

    PTH stimulates osteoblastic cells to form new bone and to produce osteoblast-osteoclast coupling factors such as RANKL. Whether osteoclasts or their activity are needed for PTH anabolism remains uncertain. We treated ovariectomized huRANKL knock-in mice with a human RANKL inhibitor denosumab (DMAb), alendronate (Aln), or vehicle for 4 weeks, followed by co-treatment with intermittent PTH for 4 weeks. Loss of bone mass and microarchitecture was prevented by Aln and further significantly improved by DMAb. PTH improved bone mass, microstructure, and strength, and was additive to Aln but not to DMAb. Aln inhibited biochemical and histomorphometrical indices of bone turnover,--i.e. osteocalcin and bone formation rate (BFR) on cancellous bone surfaces-, and Dmab inhibited them further. However Aln increased whereas Dmab suppressed osteoclast number and surfaces. PTH significantly increased osteocalcin and bone formation indices, in the absence or presence of either antiresorptive, although BFR remained lower in presence of Dmab. To further evaluate PTH effects in the complete absence of osteoclasts, high dose PTH was administered to RANK(-/-) mice. PTH increased osteocalcin similarly in RANK(-/-) and WT mice. It also increased BMD in RANK(-/-) mice, although less than in WT. These results further indicate that osteoclasts are not strictly required for PTH anabolism, which presumably still occurs via stimulation of modeling-based bone formation. However the magnitude of PTH anabolic effects on the skeleton, in particular its additive effects with antiresorptives, depends on the extent of the remodeling space, as determined by the number and activity of osteoclasts on bone surfaces.

  3. Research of stimulants and anabolic steroids in dietary supplements.

    PubMed

    Baume, N; Mahler, N; Kamber, M; Mangin, P; Saugy, M

    2006-02-01

    The purpose of this study was to analyze the composition of 103 dietary supplements bought on the internet. The supplements were dispatched in four different categories according to their announced contents [creatine, prohormones, "mental enhancers" and branched chain amino acids (BCAA)]. All the supplements were screened for the presence of stimulants and main anabolic steroids parent compounds. At the same time, the research was focused on the precursors and metabolites of testosterone and nandrolone. The study pointed out three products containing an anabolic steroid, metandienone, in a very high amount. The ingestion of such products induced a high quantity of metandienone metabolites in urines that would be considered as a positive antidoping test. The results have also shown that one creatine product and three "mental enhancers" contained traces of hormones or prohormones not claimed on the labels and 14 prohormone products contained substances other than those indicated by the manufacturer. The oral intake of the creatine product revealed the presence of the two main nandrolone metabolites (19-norandrosterone and 19-noretiocholanolone) in urine.

  4. Antagonizing the calcium-sensing receptor: towards new bone anabolics?

    PubMed

    Riccardi, Daniela

    2012-06-01

    With a rise in the aging population, the global osteoporosis market represents a major unmet need and one of the greatest challenges for the pharmaceutical companies. Currently bisphosphonates constitute the mainstay antiosteoporotic treatment. They inhibit osteoclast-dependent bone resorption, and substantially reduce the risk of vertebral and non-vertebral fractures. However, bisphosphonates are only marginally effective in subjects with significant loss of bone mineral density. Furthermore, safety concerns have recently been raised due to an increased risk of low-energy fractures associated with long-term bisphosphonate treatment; hence the need for new osteoanabolic drugs. Transient fluctuations in plasma parathyroid hormone (PTH) are a well-established bone anabolic stimulus and efforts have aimed at identifying new medical therapies that can reduce the risk of vertebral and non-vertebral fractures and increase bone mineral density through modifications of circulating PTH. Two approaches have recently emerged in the search for new bone anabolics: a) administration of exogenous PTH, and b) administration of compounds, which evoke transient release of endogenous PTH, namely calcilytics. This review will focus on the potential use of PTH modifying agents as the new osteoanabolics.

  5. Selling androgenic anabolic steroids by the pound: identification and analysis of popular websites on the Internet.

    PubMed

    Cordaro, F G; Lombardo, S; Cosentino, M

    2011-12-01

    Internet websites offering androgenic anabolic steroids (AAS) were identified and available products were examined. Keywords for the website search were: "anabolic steroids," "anabolic steroids buy," "anabolic steroid purchase." The first 10 websites offering AAS in the first 10 pages of results were considered. At least two AAS-containing products per website were selected. Thirty AAS-selling websites were identified, mainly located in the United States (46.7%) and Europe (30%). Most websites sold other anabolic/ergogenic products (clenbuterol, 76.7%; GH/IGF, 60.0%; thyroid hormones, 46.7%; erythropoietin, 30.0%; insulin, 20.0%) or products for AAS-related adverse effects (mainly: estrogen antagonists, 63.3%; products for erectile dysfunction, 56.7%; 5α-reductase inhibitors, 33.3%; anti-acne products, 33.3%). AAS were sold as medicines (69.6%) or as dietary supplements (30.4%). AAS in medicines were mainly: nandronole (20.4%), methandrostenolone (18.4%), and testosterone (12.2%). Dietary supplements contained mainly DHEA and included several fake compounds. Manufacturers were declared for 97.9% of medicines and 66.7% of dietary supplements; however, several manufacturers were not found on the Internet. Described benefits were usually few adverse effects and no estrogenicity. Toxicity was seldom reported and presented as mild. Recommended doses were two-fourfold higher than current medical recommendations. In conclusion, misleading information and deceiving practices were common findings on AAS-selling websites, indicating their deleterious potential for public health.

  6. Jasmonate Hormone: Regulating Synthesis of Reduced Carbon Compounds in Plants

    SciTech Connect

    Browse, John

    2016-05-13

    Our original interest in understanding the role of jasmonate (JA) in regulating the final stages of stamen and pollen development led to our discovery of the JAZ repressors, and the molecular mechanism of JA action is now a second important focus of our research. The specific goals for this grant period are to: 1. Investigate the generation and clearance of the hormone with emphasis on the regulation of the OPR3 enzyme and the hydrolysis of JA-Ile. 2. Use dominant-negative and overexpression constructs to explore the role of the MYC5 transcription factor in initiating and regulating JA responses. 3. Investigate specific JAZ protein interactions that will help us to recognize and understand the extended network of processes, such as sulfur nutrition, that interface with JA signaling. The COI1 F-Box protein is a JA-Ile coreceptor and coi1 mutant plants lack JA responses. We have tested the possibility that sites of JA action can be probed by using tissue-specific promoters to drive expression of a COI1-YFP fusion protein in coi1 mutant plants deficient in stamen and pollen function. When we expressed COI1 behind a filament-specific promoter (from the DAD1 gene), filament elongation was restored but not anther dehiscence or pollen function. Three tapetum specific promoters, all failed to restore any of these three functions but, unexpectedly, a promoter active in the stomium and epidermal cells, restored both pollen function and anther dehiscence. Most importantly, our results demonstrate the power of promoter::COI1-YFP constructs in revealing the primary sites of JA-regulated gene expression that control developmental and other responses in neighboring tissues. We now plan to use this new tool to test current hypotheses about JA action in other organs of the plant. The MYC2, MYC3, and MYC4 proteins are the primary transcription factors initiating defense and root growth responses to JA signaling. However, transgenic plants overexpressing these proteins do not show

  7. Sexual functioning of male anabolic steroid abusers.

    PubMed

    Moss, H B; Panzak, G L; Tarter, R E

    1993-02-01

    The effects of anabolic steroid use on male sexual behavior were assessed using a structured clinical interview administered to male body builders currently using steroids, and to two comparison groups (body builders with a past but not current history of steroid use, and a group of "natural" body builders who had never used steroids). Current anabolic steroid users had a significantly higher coital and orgasmic frequency than did comparison athletes. They also reported a significantly higher incidence of erectile difficulties during the past month. Beliefs concerning the sexually stimulating effects of steroids did not correlate with the frequencies of specific sexual behaviors. The data support the contention that anabolic steroids, as androgenic compounds, enhance sexual desire.

  8. Ecdysteroids: A novel class of anabolic agents?

    PubMed

    Parr, M K; Botrè, F; Naß, A; Hengevoss, J; Diel, P; Wolber, G

    2015-06-01

    Increasing numbers of dietary supplements with ecdysteroids are marketed as "natural anabolic agents". Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class "S1.2 Other Anabolic Agents" of the list of prohibited substances of the World Anti-Doping Agency.

  9. Ecdysteroids: A novel class of anabolic agents?

    PubMed Central

    Botrè, F; Naß, A; Hengevoss, J; Diel, P; Wolber, G

    2015-01-01

    Increasing numbers of dietary supplements with ecdysteroids are marketed as “natural anabolic agents”. Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class “S1.2 Other Anabolic Agents” of the list of prohibited substances of the World Anti-Doping Agency. PMID:26060342

  10. Impact of Four Weeks of a Multi-Ingredient Performance Supplement on Muscular Strength, Body Composition, and Anabolic Hormones in Resistance-Trained Young Men.

    PubMed

    Kreipke, Vince C; Allman, Brittany R; Kinsey, Amber W; Moffatt, Robert J; Hickner, Robert C; Ormsbee, Michael J

    2015-12-01

    Although multi-ingredient performance supplements (MIPS) have increased in popularity because of their array of ergogenic ingredients, their efficacy and safety remain in question. The objective of this study was to determine the impact of supplementation with T+ (SUP; Onnit Labs, Austin, TX, USA), an MIPS containing long jack root, beta-alanine, and branched-chain amino acids, and other proprietary blends, on strength, body composition, and hormones in young resistance-trained men. Subjects were randomized to consume either T+ (SUP; n = 14; age, 21 ± 3 years; body fat, 18.3 ± 4.7%) or an isocaloric placebo (PL; n = 13; age, 21 ± 3 years; body fat, 21.5 ± 6.2%) for 4 weeks. Both groups underwent a progressive, 4-week high-intensity resistance training protocol. Before and after the training protocol, mood state, body composition, blood hormones (also collected at midpoint), and maximal strength were measured. SUP had significantly greater increases in bench press (SUP, 102 ± 16 kg to 108 ± 16 kg vs. PL, 96 ± 22 kg to 101 ± 22 kg; p < 0.001) and total weight lifted (SUP, 379 ± 59 kg to 413 ± 60 kg vs. PL, 376 ± 70 kg to 400 ± 75 kg; p < 0.001) compared with PL. Additionally, deadlift strength relative to total body mass (calculated as weight lifted/body mass; kg:kg) (2.08 ± 0.18 to 2.23 ± 0.16; p = 0.036) and lean mass (2.55 ± 0.19 to 2.72 ± 0.16; p = 0.021) increased significantly in SUP but not PL (2.02 ± 0.30 to 2.15 ± 0.36 and 2.56 ± 0.31 to 2.70 ± 0.36, respectively). No other significant differences were detected between groups for the remaining variables. Supplementing with SUP enhanced resistance training adaptations independent of hormonal status, and thus SUP use may warrant inclusion into peri-workout nutrition regimens. This study was registered with clinicaltrials.gov (identifier: NCT01971723).

  11. Compounded non-FDA-approved menopausal hormone therapy prescriptions have increased: results of a pharmacy survey.

    PubMed

    Pinkerton, JoAnn V; Constantine, Ginger D

    2016-04-01

    From a survey of compounding pharmacists, specific questions regarding compounded menopausal hormone therapy were used to estimate compounded hormone therapy (CHT) prescribing in the United States. A national online survey was conducted by Rose Research--a market research company consisting of 12,250 US pharmacists from independent community pharmacies (ICPs) and compounding pharmacies (CPs). Pharmacists who completed the survey and met the prespecified criteria were eligible. Data from the survey were extrapolated to estimate overall CHT prescription volume and annual costs of CHT prescriptions for the United States based upon industry data from the National Community Pharmacists Association and IBISWorld. Surveys were completed by 483 pharmacies, including 365 ICPs and 118 CPs. On the basis of the survey responses and extrapolated industry data, an estimated 26 to 33 million CHT prescriptions were filled annually, with total sales estimated at $1.3 to $1.6 billion. CPs (vs ICPs) accounted for a higher proportion of CHT prescriptions. More than half of the ICPs (52%) and CPs (75%) expected continued compounding business growth, with most predicting 5% to 25% growth within 2 years, despite the potential effect of restrictive legislation regarding compounding. On the basis of extrapolated data from numbers of prescriptions reported by pharmacists participating in the survey, the volume of CHT seems to approach that of Food and Drug Administration (FDA)-approved menopausal hormone therapy, and growth in the CHT market is expected. Thus, physicians should educate themselves and the women consulting them about the differences between the FDA-approved and the less-tested CHT formulations. More research on the efficacy, safety, and consistency of non-FDA-approved CHT is needed.

  12. Bioidentical compounded hormones: a pharmacokinetic evaluation in a randomized clinical trial.

    PubMed

    Sood, Richa; Warndahl, Roger A; Schroeder, Darrell R; Singh, Ravinder J; Rhodes, Deborah J; Wahner-Roedler, Dietlind; Bahn, Rebecca S; Shuster, Lynne T

    2013-04-01

    Bioidentical compounded hormone therapy is popular among patients, but providers do not have pharmacokinetic information or dosing guidelines for these preparations. Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice. We conducted a randomized, blinded, four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream (Bi-est (80:20); 2.0, 2.5, or 3.0 mg)+compounded oral progesterone 100 mg, or to a conventional estradiol patch (Vivelle-Dot™ 0.05 mg)+Prometrium™ 100mg. Serum levels of estrone, estradiol, estriol, and progesterone were obtained at multiple time intervals during the first 24-h, and at steady-state. Results were analyzable for 37/40 women. Study medications were well tolerated. The AUC at 24h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch. The difference was statistically significant for Bi-est 2.0mg (AUC-estradiol=181 vs. 956; p<0.001) and 2.5mg (AUC-estradiol=286 vs. 917; p<0.001). Estriol levels remained low in all study arms. Serum progesterone levels were comparable in conventional vs. compounded groups. This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the standard-dose estradiol patch. To find comparable doses, further studies are needed. This successfully conducted randomized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Role of biofilms in sorptive removal of steroidal hormones and 4-nonylphenol compounds from streams

    USGS Publications Warehouse

    Writer, J.H.; Ryan, J.N.; Barber, L.B.

    2011-01-01

    Stream biofilms play an important role in geochemical processing of organic matter and nutrients, however, the significance of this matrix in sorbing trace organic contaminants is less understood. This study focused on the role of stream biofilms in sorbing steroidal hormones and 4-nonylphenol compounds from surface waters using biofilms colonized in situ on artificial substrata and subsequently transferred to the laboratory for controlled batch sorption experiments. Steroidal hormones and 4-nonylphenol compounds readily sorb to stream biofilms as indicated by organic matter partition coefficients (K om, L kg-1) for 17??-estradiol (102.5-2.8 L kg-1), 17??-ethynylestradiol (102.5-2.9 L kg -1), 4-nonylphenol (103.4-4.6 L kg-1), 4-nonylphenolmonoethoxylate (103.5-4.0 L kg-1), and 4-nonylphenoldiethoxylate (103.9-4.3 L kg-1). Experiments using water quality differences to induce changes in the relative composition of periphyton and heterotrophic bacteria in the stream biofilm did not significantly affect the sorptive properties of the stream biofilm, providing additional evidence that stream biofilms will sorb trace organic compounds under of variety of environmental conditions. Because sorption of the target compounds to stream biofilms was linearly correlated with organic matter content, hydrophobic partition into organic matter appears to be the dominant mechanism. An analysis of 17??-estradiol and 4-nonylphenol hydrophobic partition into water, biofilm, sediment, and dissolved organic matter matrices at mass/volume ratios typical of smaller rivers showed that the relative importance of the stream biofilm as a sorptive matrix was comparable to bed sediments. Therefore, stream biofilms play a primary role in attenuating these compounds in surface waters. Because the stream biofilm represents the base of the stream ecosystem, accumulation of steroidal hormones and 4-nonylphenol compounds in the stream biofilm may be an exposure pathway for organisms in higher trophic

  14. Compounded non-FDA–approved menopausal hormone therapy prescriptions have increased: results of a pharmacy survey

    PubMed Central

    Pinkerton, JoAnn V.; Constantine, Ginger D.

    2016-01-01

    Abstract Objective: From a survey of compounding pharmacists, specific questions regarding compounded menopausal hormone therapy were used to estimate compounded hormone therapy (CHT) prescribing in the United States. Methods: A national online survey was conducted by Rose Research—a market research company consisting of 12,250 US pharmacists from independent community pharmacies (ICPs) and compounding pharmacies (CPs). Pharmacists who completed the survey and met the prespecified criteria were eligible. Data from the survey were extrapolated to estimate overall CHT prescription volume and annual costs of CHT prescriptions for the United States based upon industry data from the National Community Pharmacists Association and IBISWorld. Results: Surveys were completed by 483 pharmacies, including 365 ICPs and 118 CPs. On the basis of the survey responses and extrapolated industry data, an estimated 26 to 33 million CHT prescriptions were filled annually, with total sales estimated at $1.3 to $1.6 billion. CPs (vs ICPs) accounted for a higher proportion of CHT prescriptions. More than half of the ICPs (52%) and CPs (75%) expected continued compounding business growth, with most predicting 5% to 25% growth within 2 years, despite the potential effect of restrictive legislation regarding compounding. Conclusions: On the basis of extrapolated data from numbers of prescriptions reported by pharmacists participating in the survey, the volume of CHT seems to approach that of Food and Drug Administration (FDA)-approved menopausal hormone therapy, and growth in the CHT market is expected. Thus, physicians should educate themselves and the women consulting them about the differences between the FDA-approved and the less-tested CHT formulations. More research on the efficacy, safety, and consistency of non-FDA–approved CHT is needed. PMID:26645819

  15. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  16. Pharmacology of anabolic steroids.

    PubMed

    Kicman, A T

    2008-06-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

  17. Abuse of anabolic androgenic steroids and related substances in sport and exercise.

    PubMed

    Bahrke, Michael S; Yesalis, Charles E

    2004-12-01

    Anabolic androgenic steroids are synthetic derivatives of testosterone, which is the primary male sex hormone. Anabolic androgenic steroids are used to enhance athletic performance and appearance. Adverse effects include those on the liver, serum lipids, psyche/behavior and reproductive system. Androstenedione is an anabolic androgenic steroid used to increase blood testosterone levels for the purposes of increasing strength, lean body mass and sexual performance. However, there is no research indicating that androstenedione, or its related compounds, significantly increases strength and/or lean body mass in humans by increasing testosterone levels. The long-term health effects of prolonged androstenedione supplementation are unknown. Dehydroepiandrosterone (DHEA) is a weak androgen also used to elevate testosterone levels, and is advertised as an anti-obesity and anti-aging supplement capable of improving libido, vitality and immunity levels. However, research demonstrates that DHEA supplementation does not increase serum testosterone concentrations or increase strength in men, and may acutely increase testosterone levels in women, thus producing a virilizing effect.

  18. Anabolic effect of plant brassinosteroid

    PubMed Central

    Esposito, Debora; Komarnytsky, Slavko; Shapses, Sue; Raskin, Ilya

    2011-01-01

    Brassinosteroids are plant-derived polyhydroxylated derivatives of 5a-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle-treated controls. The effect of HB administration increased slightly in animals fed a high-protein diet (protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity when tested in the Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor in vitro. HB treatment was also associated with an improved physical fitness of untrained healthy rats, as evident from a 6.7% increase in lower extremity strength, measured by grip test. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibers and the cross-sectional area of type I and type IIa fibers. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side-effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.—Esposito, D., Komarnytsky, S., Shapses, S., Raskin, I. Anabolic effect of plant brassinosteroid. PMID:21746867

  19. Influence of anabolic combinations of an androgen plus an estrogen on biochemical pathways in bovine uterine endometrium and ovary.

    PubMed

    Becker, C; Riedmaier, I; Reiter, M; Tichopad, A; Groot, M J; Stolker, A A M; Pfaffl, M W; Nielen, M F W; Meyer, H H D

    2011-07-01

    The application of anabolic steroids in food producing animals is forbidden in the EU since 1988, but the abuse of such drugs is a potential problem. The existing test systems are based on known compounds and can be eluded by newly emerging substances. The examination of physiological effects of anabolic hormones on different tissues to indirectly detect misuse might overcome this problem. Two studies were conducted with post-pubertal 24-months old Nguni heifers and pre-pubertal female 2-4 weeks old Holstein Friesian calves, respectively. The animals of the accordant treatment groups were administered combinations of estrogenic and androgenic compounds. The measurement of the gene expression pattern was undertaken with RT-qPCR. Target genes of different functional groups (receptors, angiogenesis, steroid synthesis, proliferation, apoptosis, nutrient metabolism and others) have been quantified. Several biochemical pathways were shown to be influenced by anabolic treatment. Both studies identified significant regulations in steroid and growth factor receptors (AR, ERβ, LHR, FSHR, Flt-1, PR, IGF-1R, Alk-6), angiogenic and tissue remodeling factors (VEGFs, FGFs, BMPs, ANGPT-2, MMPs, TIMP-2, CTSB), steroid synthesis (S5A1, HSD17, CYP19A1), proliferation (TNFα, IGF-1, IGFBPs, p53, c-fos; CEBPD, c-kit), apoptosis (CASP3, FasL, p53) and others (C7, INHA, STAR). Several genes were regulated to opposite directions in post-pubertal compared to pre-pubertal animals. PCA for Nguni heifers demonstrated a distinct separation between the control and the treatment group. In conclusion, anabolics modify hormone sensitivity and steroid synthesis, and they induce proliferative effects in the whole reproductive tract (uterus and ovary) as well as anti-angiogenic effects in the ovary. However, the extent will depend on the developmental stage of the animals.

  20. Influence of the dosing frequency of parathyroid hormone-(1-38) on its anabolic effect in bone and on the balance of calcium, phosphorus and magnesium.

    PubMed

    Riond, J L; Goliat-von Fischer, I; Küffer, B; Toromanoff, A; Forrer, R

    1998-06-01

    The effect of the frequency of administration of synthetic human parathyroid hormone fragment 1-38 [hPTH-(1-38)] on bone formation and on the balance of calcium, phosphorus, and magnesium was investigated in 32 9-week-old female Sprague-Dawley rats, using a randomly complete block design. Rats received subcutaneously during 14 days either the vehicle solution once a day or 50 micrograms hPTH-(1-38)/kg BW once a day at 8:00 a.m., twice a day at 8:00 a.m. and 5:00 p.m. or three times a day at 8:00 a.m., 0:30 p.m., and 5:00 p.m. The balance study was performed during the last 48 h of the hPTH-(1-38) treatment schedule after which femora, tibiae, and lumbar vertebrae were removed for the determination of the dry weight, volume, and contents of Ca, P, Mg, hydroxyproline, and DNA. PTH treatment was associated with a significant increase of the apparent intestinal absorption of Ca, P, and Mg. Mean urinary Ca excretion augmented with the increase of the frequency of dosing. Urinary Ca excretion correlated negatively with the Ca apparent intestinal absorption and with the Ca content of the tibiae in the 2 groups with the highest frequency of dosing. The mean Ca, P, and Mg balances, the mean contents of bone Ca, P, and Mg and the mean bone dry weights were significantly increased with PTH treatment. In contrast to the mean volume of tibiae which was not affected by the PTH administration, the mean volume of the fifth lumbar vertebrae increased with the treatment. With the 2 times and 3 times daily treatments, mean hydroxyproline concentrations in the femora were significantly higher than the control values. An increase of the mean hydroxyproline content of the third lumbar vertebrae was evidenced with the 1 time and 2 times daily treatment, but the mean of the highest frequency of dosing was not different from that of the control group. The DNA content of femoral and of the fourth lumbar vertebrae significantly decreased with the frequency of dosing.

  1. Anabolic steroid-induced hypogonadism--towards a unified hypothesis of anabolic steroid action.

    PubMed

    Tan, R S; Scally, M C

    2009-06-01

    Anabolic steroid-induced hypogonadism (ASIH) is the functional incompetence of the testes with subnormal or impaired production of testosterone and/or spermatozoa due to administration of androgens or anabolic steroids. Anabolic-androgenic steroid (AAS), both prescription and nonprescription, use is a cause of ASIH. Current AAS use includes prescribing for wasting associated conditions. Nonprescription AAS use is also believed to lead to AAS dependency or addiction. Together these two uses account for more than four million males taking AAS in one form or another for a limited duration. While both of these uses deal with the effects of AAS administration they do not account for the period after AAS cessation. The signs and symptoms of ASIH directly impact the observation of an increase in muscle mass and muscle strength from AAS administration and also reflect what is believed to demonstrate AAS dependency. More significantly, AAS prescribing after cessation adds the comorbid condition of hypogonadism to their already existing chronic illness. ASIH is critical towards any future planned use of AAS or similar compound to effect positive changes in muscle mass and muscle strength as well as an understanding for what has been termed anabolic steroid dependency. The further understanding and treatments that mitigate or prevent ASIH could contribute to androgen therapies for wasting associated diseases and stopping nonprescription AAS use. This paper proposes a unified hypothesis that the net effects for anabolic steroid administration must necessarily include the period after their cessation or ASIH.

  2. Consequences of use of anabolic androgenic steroids.

    PubMed

    Casavant, Marcel J; Blake, Kathleen; Griffith, Jill; Yates, Andrew; Copley, LaRae M

    2007-08-01

    Whether providing anticipatory guidance to the young adolescent patient, conducting a preparticipation examination on a young athlete, or treating a sick user of anabolic androgenic steroids (AASs), the primary care physician must be familiar with the adverse consequences of the use of these compounds. This article reviews the endocrine, cardiovascular, neuropsychiatric, musculoskeletal, hematologic, hepatic, and miscellaneous effects of AASs, highlighting effects reported in children and adolescents, and relying on consequences in adults when pediatric data is unavailable.

  3. Pharmacology of anabolic steroids

    PubMed Central

    Kicman, A T

    2008-01-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic–androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided. PMID:18500378

  4. Project Right Way: An Anabolic Steroid Education Program.

    ERIC Educational Resources Information Center

    Nutter, June

    There is increasing concern by medical experts in this country about the use of anabolic steroids by teenagers. Over one million Americans are believed to be currently using or have used the synthetic hormones in the past. While drug testing and a reduction in the supply of the drugs appear to be reducing the number of adult users, use by…

  5. Role of biofilms in sorptive removal of steroidal hormones and 4-nonylphenol compounds from streams

    USGS Publications Warehouse

    Writer, Jeffrey H.; Ryan, Joseph N.; Barber, Larry B.

    2011-01-01

    Stream biofilms play an important role in geochemical processing of organic matter and nutrients, however, the significance of this matrix in sorbing trace organic contaminants is less understood. This study focused on the role of stream biofilms in sorbing steroidal hormones and 4-nonylphenol compounds from surface waters using biofilms colonized in situ on artificial substrata and subsequently transferred to the laboratory for controlled batch sorption experiments. Steroidal hormones and 4-nonylphenol compounds readily sorb to stream biofilms as indicated by organic matter partition coefficients (Kom, L kg–1) for 17β-estradiol (102.5–2.8 L kg–1), 17α-ethynylestradiol (102.5–2.9 L kg–1), 4-nonylphenol (103.4–4.6 L kg–1), 4-nonylphenolmonoethoxylate (103.5–4.0 L kg–1), and 4-nonylphenoldiethoxylate (103.9–4.3 L kg–1). Experiments using water quality differences to induce changes in the relative composition of periphyton and heterotrophic bacteria in the stream biofilm did not significantly affect the sorptive properties of the stream biofilm, providing additional evidence that stream biofilms will sorb trace organic compounds under of variety of environmental conditions. Because sorption of the target compounds to stream biofilms was linearly correlated with organic matter content, hydrophobic partition into organic matter appears to be the dominant mechanism. An analysis of 17β-estradiol and 4-nonylphenol hydrophobic partition into water, biofilm, sediment, and dissolved organic matter matrices at mass/volume ratios typical of smaller rivers showed that the relative importance of the stream biofilm as a sorptive matrix was comparable to bed sediments. Therefore, stream biofilms play a primary role in attenuating these compounds in surface waters. Because the stream biofilm represents the base of the stream ecosystem, accumulation of steroidal hormones and 4-nonylphenol compounds in the stream biofilm may be an exposure pathway for

  6. The effects of six weeks of supplementation with multi-ingredient performance supplements and resistance training on anabolic hormones, body composition, strength, and power in resistance-trained men

    PubMed Central

    2012-01-01

    Background Resistance training (RT) enhances muscle protein synthesis and hypertrophy while increasing strength and power. Some multi-ingredient performance supplements (MIPS) have been shown to augment the physiological improvements associated with RT. The purpose of this study was to investigate the impact of specific pre- and post-workout MIPS on anabolic hormones, body composition, muscle strength, and power in resistance-trained men participating in a periodized RT program. Methods Twenty-four ( mean ± SE; 24.0 ± 0.9 years; 180.5 ± 5.8 cm; 83.7 ± 0.5 kg) resistance-trained men completed 6 wks of periodized RT (3x/wk). Participants were assigned to one of two groups based upon maximal voluntary contraction of the quadriceps (Biodex) to lean mass (LM) ratio. Group 1 (n = 13; MIPS) consumed one serving of NO-Shotgun® (whey protein, casein protein, branched-chain amino acids, creatine, beta alanine, and caffeine) before each workout and one serving of NO-Synthesize® (whey protein, casein protein, branched-chain amino acids, creatine, and beta alanine; Vital Pharmaceuticals, Inc., Davie, FL) immediately after each workout and on non-RT days. Group 2 (n = 11; Placebo; PLA) consumed a flavor-matched isocaloric maltodextrin placebo. Serum insulin-like growth factor 1, human growth hormone, testosterone, body composition (DXA), circumferences, 1-repetition maximal strength (1RM) of the upper (chest press) and lower body (leg press), and anaerobic power (Wingate test) were assessed before and after the intervention. Statistical analysis included a 2 × 2 (group x time) ANOVA with repeated measures. Tukey LSD post hoc tests were used to examine pairwise differences. Significance was set at p < 0.05. Results There was a main time effect (p = 0.035) for testosterone to increase, but no differences between groups were observed. There were no differences in the other blood hormones. Group x time interactions were observed for LM

  7. Pathological changes in anabolic androgenic steroid users.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2015-07-01

    Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  8. Anabolic steroids and head injury.

    PubMed

    Mills, James D; Bailes, Julian E; Turner, Ryan C; Dodson, Sean C; Sakai, Jun; Maroon, Joseph C

    2012-01-01

    The suggestion has been made that neurological changes seen in the syndrome of chronic traumatic encephalopathy may be due to exogenous anabolic steroid use rather than traumatic brain injury. To determine whether administration of anabolic steroids alters the pathophysiology of traumatic brain injury. Sixty adult male Sprague-Dawley rats and a linear acceleration model of traumatic brain injury were used. Experimental groups were (1) preinjury anabolic steroids, (2) preinjury placebo carrier, (3) anabolic steroids without injury, (4) no steroids and no injury, (5) postinjury placebo carrier, and (6) postinjury anabolic steroids. Following a 30-day recovery, rats were euthanized, and brainstem white matter tracts underwent fluorescent immunohistochemical processing and labeling of β-amyloid precursor protein (APP), a marker of axonal injury. Digital imaging and statistical analyses were used to determine whether anabolic steroid administration resulted in a significant change in the number of injured axons. There was no statistically significant difference in number of APP-positive axons by immunohistochemical analysis between respective anabolic steroid and placebo groups. Using a standard acceleration-deceleration model of mild traumatic brain injury, we have shown successful visualization of traumatically injured axons with antibody staining of APP. Our results indicate no statistically significant effect of anabolic steroids on the number of APP-positive axons. With the use of this model, and within its limitations, we see no adverse effect or causative role of anabolic steroid administration on the brain following mild traumatic brain injury using APP counts as a marker for anatomic injury.

  9. Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.

    PubMed

    Troina, A A; Figueiredo, M S; Passos, M C F; Reis, A M; Oliveira, E; Lisboa, P C; Moura, E G

    2012-07-01

    We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil+SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40 mg of SDG/100g diet (SDG) or diet added 40 mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14th day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-β estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups.

  10. New Insights into the Role of Anabolic Interventions in Dialysis Patients with Protein Energy Wasting

    PubMed Central

    Dong, Jie; Ikizler, T. Alp

    2010-01-01

    Purpose of review Patients on maintenance dialysis commonly develop protein-energy wasting (PEW), which is associated with poor survival. There have been several advances in anabolic interventions aimed at improving PEW in these patients in recent years. Recent findings Oral or parenteral nutritional supplementation, especially if administered during dialysis, improves net protein anabolism in chronic hemodialysis (CHD) patients. These beneficial effects have been extended to long-term benefits in recent clinical trials. Resistance exercise, alone or combined with intradialytic oral nutrition supplementation also improves net protein balance in the acute setting although recent studies indicated a limited beneficial effect of long-term exercise alone on muscle protein accretion in CHD patients. Anabolic agents such as growth hormone and androgens have been shown to exert significant benefits on visceral protein stores, muscle mass and strength. Ghrelin, a hormone with combined orexigenic and anti-inflammatory effects, is a potential new nutritional intervention in maintenance dialysis patients. Summary Existing anabolic therapeutic strategies have proven to be effective in improving PEW in maintenance dialysis patients. Combined anabolic interventions and several new and established anabolic hormones represent as further promising nutritional interventions. Large-scale randomized controlled trials examining the effects of anabolic interventions on mortality and morbidity are still lacking. PMID:19713839

  11. Test methods: anabolics.

    PubMed

    Saugy, M; Cardis, C; Robinson, N; Schweizer, C

    2000-03-01

    In the International Olympic Committee (IOC) accredited laboratories, specific methods have been developed to detect anabolic steroids in athletes' urine. The technique of choice to achieve this is gas-chromatography coupled with mass spectrometry (GC-MS). In order to improve the efficiency of anti-doping programmes, the laboratories have defined new analytical strategies. The final sensitivity of the analytical procedure can be improved by choosing new technologies for use in detection, such as tandem mass spectrometry (MS-MS) or high resolution mass spectrometry (HRMS). A better sample preparation using immuno-affinity chromatography (IAC) is also a good tool for improving sensitivity. These techniques are suitable for the detection of synthetic anabolic steroids whose structure is not found naturally in the human body. The more and more evident use, on a large scale, of substances chemically similar to the endogenous steroids obliges both the laboratory and the sports authorities to use the steroid profile of the athlete in comparison with reference ranges from a population or with intraindividual reference values.

  12. Anabolic Steroid Use: Federal Efforts to Prevent and Reduce Anabolic Steroid Abuse among Teenagers. Report to the Committee on Oversight and Government Reform, House of Representatives. GAO-08-15

    ERIC Educational Resources Information Center

    Government Accountability Office, 2007

    2007-01-01

    The abuse of anabolic steroids by teenagers--that is, their use without a prescription--is a health concern. Anabolic steroids are synthetic forms of the hormone testosterone that can be taken orally, injected, or rubbed on the skin. Although a 2006 survey funded by the National Institute on Drug Abuse (NIDA) found that less than 3 percent of 12th…

  13. [Abuse of anabolic steroids and its impact on thyroid function].

    PubMed

    Fortunato, Rodrigo S; Rosenthal, Doris; Carvalho, Denise P de

    2007-12-01

    The use of anabolic steroids to increase physical performance and for aesthetic ends has reached alarming indices in the last three decades. Besides the desired actions, several collateral effects have been described in the literature, such as the development of some types of cancer, ginecomasty, peliosis hepatis, renal insufficiency, virilization, amongst others. The most proeminent effect on human thyroid function is the reduction of thyroxine binding globulin (TBG), with consequent reductions of total serum T3 and T4, depending however on the susceptibility of the drug to aromatization and subsequent transformation into estrogen. In rats, anabolic steroids also act in the peripheral metabolism of thyroid hormones and seem to exert an important proliferative effect on thyroid cells. Thus, the aim of the present paper is to review data on the effect of supraphysiological doses of anabolic steroids on thyroid function, showing the danger that indiscriminate use of these drugs can cause to health.

  14. Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor.

    PubMed

    Ren, Xiao-Min; Zhang, Yin-Feng; Guo, Liang-Hong; Qin, Zhan-Fen; Lv, Qi-Yan; Zhang, Lian-Ying

    2015-02-01

    Perfluoroalkyl compounds (PFCs) have been shown to disrupt thyroid functions through thyroid hormone receptor (TR)-mediated pathways, but direct binding of PFCs with TR has not been demonstrated. We investigated the binding interactions of 16 structurally diverse PFCs with human TR, their activities on TR in cells, and the activity of perfluorooctane sulfonate (PFOS) in vivo. In fluorescence competitive binding assays, most of the 16 PFCs were found to bind to TR with relative binding potency in the range of 0.0003-0.05 compared with triiodothyronine (T3). A structure-binding relationship for PFCs was observed, where fluorinated alkyl chain length longer than ten, and an acid end group were optimal for TR binding. In thyroid hormone (TH)-responsive cell proliferation assays, PFOS, perfluorohexadecanoic acid, and perfluorooctadecanoic acid exhibited agonistic activity by promoting cell growth. Furthermore, similar to T3, PFOS exposure promoted expression of three TH upregulated genes and inhibited three TH downregulated genes in amphibians. Molecular docking analysis revealed that most of the tested PFCs efficiently fit into the T3-binding pocket in TR and formed a hydrogen bond with arginine 228 in a manner similar to T3. The combined in vitro, in vivo, and computational data strongly suggest that some PFCs disrupt the normal activity of TR pathways by directly binding to TR.

  15. Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon

    USGS Publications Warehouse

    Lerner, Darren T.; Sheridan, Mark A.; McCormick, Stephen D.

    2012-01-01

    Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10 days with 2 μg g−1 17β-estradiol (E2) or 150 μg g−1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30 μg g−1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5 mM in FW and increased 10.5 mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na+/K+-ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na+/K+-ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.

  16. Anabolic Steroids...What's the Hype?...

    ERIC Educational Resources Information Center

    Landry, Gregory L.; Wagner, Lauris L.

    This pamphlet uses a question-and-answer format to examine the use and abuse of anabolic steroids. It begins by explaining that all steroids are not anabolic steroids and that anabolic steroids are those used specifically to build muscles quickly. Medical uses of anabolic steroids are reviewed; how people get steroids, how they take them, and…

  17. Anabolic Steroids...What's the Hype?...

    ERIC Educational Resources Information Center

    Landry, Gregory L.; Wagner, Lauris L.

    This pamphlet uses a question-and-answer format to examine the use and abuse of anabolic steroids. It begins by explaining that all steroids are not anabolic steroids and that anabolic steroids are those used specifically to build muscles quickly. Medical uses of anabolic steroids are reviewed; how people get steroids, how they take them, and…

  18. Occurrence of pharmaceuticals, hormones, and organic wastewater compounds in Pennsylvania waters, 2006-09

    USGS Publications Warehouse

    Reif, Andrew G.; Crawford, J. Kent; Loper, Connie A.; Proctor, Arianne; Manning, Rhonda; Titler, Robert

    2012-01-01

    Concern over the presence of contaminants of emerging concern, such as pharmaceutical compounds, hormones, and organic wastewater compounds (OWCs), in waters of the United States and elsewhere is growing. Laboratory techniques developed within the last decade or new techniques currently under development within the U.S. Geological Survey now allow these compounds to be measured at concentrations in nanograms per liter. These new laboratory techniques were used in a reconnaissance study conducted by the U.S. Geological Survey, in cooperation with the Pennsylvania Department of Environmental Protection, to determine the occurrence of contaminants of emerging concern in streams, streambed sediment, and groundwater of Pennsylvania. Compounds analyzed for in the study are pharmaceuticals (human and veterinary drugs), hormones (natural and synthetic), and OWCs (detergents, fragrances, pesticides, industrial compounds, disinfectants, polycyclic aromatic hydrocarbons, fire retardants and plasticizers). Reconnaissance sampling was conducted from 2006 to 2009 to identify contaminants of emerging concern in (1) groundwater from wells used to supply livestock, (2) streamwater upstream and downstream from animal feeding operations, (3) streamwater upstream from and streamwater and streambed sediment downstream from municipal wastewater effluent discharges, (4) streamwater from sites within 5 miles of drinking-water intakes, and (5) streamwater and streambed sediment where fish health assessments were conducted. Of the 44 pharmaceutical compounds analyzed in groundwater samples collected in 2006 from six wells used to supply livestock, only cotinine (a nicotine metabolite) and the antibiotics tylosin and sulfamethoxazole were detected. The maximum concentration of any contaminant of emerging concern was 24 nanograms per liter (ng/L) for cotinine, and was detected in a groundwater sample from a Lebanon County, Pa., well. Seven pharmaceutical compounds including acetaminophen

  19. Anabolic effect of plant brassinosteroid.

    PubMed

    Esposito, Debora; Komarnytsky, Slavko; Shapses, Sue; Raskin, Ilya

    2011-10-01

    Brassinosteroids are plant-derived polyhydroxylated derivatives of 5a-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC(50) 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle-treated controls. The effect of HB administration increased slightly in animals fed a high-protein diet (protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity when tested in the Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor in vitro. HB treatment was also associated with an improved physical fitness of untrained healthy rats, as evident from a 6.7% increase in lower extremity strength, measured by grip test. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibers and the cross-sectional area of type I and type IIa fibers. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side-effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.

  20. Abaloparatide: Recombinant human PTHrP (1-34) anabolic therapy for osteoporosis.

    PubMed

    Chew, Chee Kian; Clarke, Bart L

    2017-03-01

    The treatment of osteoporosis is generally either by inhibition of bone resorption with antiresorptive agents or by stimulation of bone formation with anabolic agents. Currently, teriparatide (recombinant human parathyroid hormone 1-34 [rhPTH (1-34)]) is the only available approved anabolic agent in the U.S. Other anabolic agents are under investigation however. Abaloparatide is recombinant human parathyroid hormone-related peptide 1-34. This agent is an anabolic agent that appears more potent than teriparatide, and it may have more rapid onset of fracture reduction than teriparatide. It is currently undergoing FDA review, with approval expected in 2017. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Cardiac effects of anabolic steroids

    PubMed Central

    Payne, J R; Kotwinski, P J; Montgomery, H E

    2004-01-01

    Anabolic steroid abuse in athletes has been associated with a wide range of adverse conditions, including hypogonadism, testicular atrophy, impaired spermatogenesis, gynaecomastia, and psychiatric disturbance. But what effect does steroid abuse have on the cardiovascular system? PMID:15084526

  2. Anabolic-Androgenic Steroids: Knowledge about, Attitude toward, and Extent of Use by High School Students.

    ERIC Educational Resources Information Center

    Yonker, R. J.; And Others

    Anabolic-androgenic steroids (AS) are pharmacologic derivatives of the hormone testosterone. They have therapeutic merit when used under a physician's prescription to treat certain hormonal imbalances and some forms of anemia; however, when taken in high doses they have a number of virilizing, feminizing, toxic, and psychological effects. This…

  3. Prescribing of FDA-approved and compounded hormone therapy differs by specialty.

    PubMed

    Constantine, Ginger D; Archer, David F; Graham, Shelli; Bernick, Brian A; Mirkin, Sebastian

    2016-10-01

    To determine the prescribing patterns of general practitioners (GPs), obstetrician/gynecologists (OB/GYNs), and wellness physicians (WPs) of menopausal hormone therapy (HT) for both compounded (CHT) and Food and Drug Administration (FDA)-approved products, using a survey of US physicians. Nine thousand one US physicians were invited to participate in a survey to report on their HT-prescribing patterns. Physicians were eligible if they prescribed HT for at least six patients per month. The survey was completed by 440 eligible physicians (893 responded of 9,001 invited) including 171 GPs, 170 OB/GYNs, and 84 WPs. Physicians prescribed HT for 15% to 30% of their female patients, with WPs numerically most likely to prescribe HT. Menopausal symptoms were the leading reason for HT prescriptions among all specialties. WPs seemed more likely to prescribe HT for general/cardiovascular health (28%), and for shorter durations, than other specialties. WPs prescribed proportionally more compounded (vs FDA-approved) estrogens/progestogens than GPs or OB/GYNs, but OB/GYNs seemed to prescribe more compounded dehydroepiandrosterone and testosterone (prescribed alone) than did others. OB/GYNs seemed least likely to consider CHT being more safe or effective than FDA-approved HT. Symptom relief was the main determinant of efficacy for all specialties; WPs also used blood (61%) or saliva testing (25%) for dose adjustment. Although all physician specialties surveyed prescribed HT, differences in prescribing CHT versus FDA-approved formulations by medical specialty/practice seemed to exist. Of those surveyed, OB/GYNs and GPs prescribed proportionally more FDA-approved HT, whereas WPs, similarly, prescribed more CHT. More discussion is needed concerning physicians' decisions to prescribe CHT versus FDA-approved formulations.

  4. Prescribing of FDA-approved and compounded hormone therapy differs by specialty

    PubMed Central

    Constantine, Ginger D.; Archer, David F.; Graham, Shelli; Bernick, Brian A.; Mirkin, Sebastian

    2016-01-01

    Abstract Objective: To determine the prescribing patterns of general practitioners (GPs), obstetrician/gynecologists (OB/GYNs), and wellness physicians (WPs) of menopausal hormone therapy (HT) for both compounded (CHT) and Food and Drug Administration (FDA)-approved products, using a survey of US physicians. Methods: Nine thousand one US physicians were invited to participate in a survey to report on their HT-prescribing patterns. Physicians were eligible if they prescribed HT for at least six patients per month. Results: The survey was completed by 440 eligible physicians (893 responded of 9,001 invited) including 171 GPs, 170 OB/GYNs, and 84 WPs. Physicians prescribed HT for 15% to 30% of their female patients, with WPs numerically most likely to prescribe HT. Menopausal symptoms were the leading reason for HT prescriptions among all specialties. WPs seemed more likely to prescribe HT for general/cardiovascular health (28%), and for shorter durations, than other specialties. WPs prescribed proportionally more compounded (vs FDA-approved) estrogens/progestogens than GPs or OB/GYNs, but OB/GYNs seemed to prescribe more compounded dehydroepiandrosterone and testosterone (prescribed alone) than did others. OB/GYNs seemed least likely to consider CHT being more safe or effective than FDA-approved HT. Symptom relief was the main determinant of efficacy for all specialties; WPs also used blood (61%) or saliva testing (25%) for dose adjustment. Conclusions: Although all physician specialties surveyed prescribed HT, differences in prescribing CHT versus FDA-approved formulations by medical specialty/practice seemed to exist. Of those surveyed, OB/GYNs and GPs prescribed proportionally more FDA-approved HT, whereas WPs, similarly, prescribed more CHT. More discussion is needed concerning physicians’ decisions to prescribe CHT versus FDA-approved formulations. PMID:27648594

  5. Biotransformation of anabolic compound methasterone with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini, and TNF-α inhibitory effect of transformed products.

    PubMed

    Ahmad, Malik Shoaib; SammerYousuf; Atia-Tul-Wahab; Jabeen, Almas; Atta-Ur-Rahman; Choudhary, M Iqbal

    2017-04-09

    Microbial transformation of methasterone (1) was investigated with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini. Biotransformation of 1 with M. phaseolina yielded metabolite 2, while metabolites 3-7 were obtained from the incubation of 1 with C. blakesleeana. Metabolites 8-13 were obtained through biotransformation with F. lini. All metabolites, except 13, were found to be new. Methasterone (1) and its metabolites 2-6, 9, 10, and 13 were then evaluated for their immunomodulatory effects against TNF-α, NO , and ROS production. Among all tested compounds, metabolite 6 showed a potent inhibition of proinflammatory cytokine TNF-α (IC50 = 8.1 ± 0.9 µg/mL), as compared to pentoxifylline used as a standard (IC50 = 94.8± 2.1 µg/mL). All metabolites were also evaluated for the inhibition of NO production at concentration of 25 µg/mL. Metabolites 6 (86.7 ± 2.3%) and 13 (62.5 ± 1.5%) were found to be the most potent inhibitors of NO as compared to the standard N(G)-monomethyl-L-arginine acetate (65.6 ± 1.1%). All metabolites were found to be non-toxic against PC3, HeLa, and 3T3 cell lines. Observed inhibitory potential of metabolites 6 and 13 against pro-inflammatory cytokine TNF-α, as well as NO production makes them interesting leads for further studies. Copyright © 2017. Published by Elsevier Inc.

  6. Use of compounded bioidentical hormone therapy in menopausal women: an opinion statement of the Women's Health Practice and Research Network of the American College of Clinical Pharmacy.

    PubMed

    McBane, Sarah E; Borgelt, Laura M; Barnes, Kylie N; Westberg, Sarah M; Lodise, Nicole M; Stassinos, Martha

    2014-01-01

    Menopausal symptoms affect a significant portion of women. Traditional treatment with manufactured hormone therapy can alleviate these symptoms, but many women and their health care providers are concerned about the risks, such as venous thromboembolism and certain types of cancer, demonstrated with manufactured hormone therapy. Compounded bioidentical hormone therapy has been proposed and is often used as a solution for these concerns. Despite this use, no data are currently available to support the claims that compounded bioidentical hormone therapy is a safer or more efficacious option compared with manufactured hormone therapy. A common misperception is that all manufactured products consist of synthetic hormones and all compounded medications consist of natural hormones; however, in fact, significant overlap exists. Several key stakeholder organizations have issued statements expressing concern about the lack of evidence regarding the efficacy and safety of compounded bioidentical hormone therapy, in addition to concerns regarding prescribing patterns. The Women's Health Practice and Research Network of the American College of Clinical Pharmacy recommends against the consistent use of compounded bioidentical hormones as a safer option compared with manufactured therapy and supports the statements of other key organizations, acknowledging the need for more robust clinical studies to evaluate the potential advantages and disadvantages of compounded bioidentical products compared with manufactured products.

  7. Exercise as an anabolic stimulus for bone.

    PubMed

    Turner, Charles H; Robling, Alexander G

    2004-01-01

    Mechanical loading provides an anabolic stimulus for bone. More importantly, the mechanosensing apparatus in bone directs osteogenesis to where it is most needed for improving bone strength. The biological processes involved in bone mechanotransduction are poorly understood and further investigation of the molecular mechanisms might uncover drug targets for osteoporosis. Several pathways are emerging from current research, including membrane ion channels, ATP signaling, and second messengers such as prostaglandins and nitric oxide. Some key molecular targets include the L-type calcium channel (alpha 1C isoform), a gadolinium-sensitive stretch-activated channel, P2Y(2) and P2X(7) purinergic receptors, EP(2) and EP(4) prostanoid receptors, and the parathyroid hormone receptor. One characteristic of the mechanosensing apparatus that has only recently been studied is the important role of desensitization. Experimental protocols that insert "rest" periods to reduce the effects of desensitization can double anabolic responses to mechanical loading. A drug therapy that suppresses desensitization pathways may provide an effective means to build bone strength.

  8. Mathematical Model of Bone Remodeling Captures the Antiresorptive and Anabolic Actions of Various Therapies.

    PubMed

    Ross, David S; Mehta, Khamir; Cabal, Antonio

    2017-01-01

    A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al. in J Bone Miner Res 28(8):1830-1836, 2013; Lemaire et al. in J Theor Biol 229:293-309, 2004; Peterson and Riggs in Bone 46:49-63, 2010; Raposo et al. in J Clin Endocrinol Metab 87(9):4330-4340, 2002; Ross et al. in J Disc Cont Dyn Sys Series B 17(6):2185-2200, 2012). We plan to use this model as a bone homeostasis platform to develop anabolic and antiresorptive compounds. The model will allow us to test hypotheses about the dynamics of compounds and to test the potential benefits of combination therapies. At the core of the model is the idealized account of osteoclast and osteoblast signaling given by Lemaire et al. (J Theor Biol 229:293-309, 2004). We have relaxed some of their assumptions about the roles of osteoprotegerin, transforming growth factor [Formula: see text], and receptor activator of nuclear factor [Formula: see text]B ligand; we have devised more detailed models of the interactions of these species. We have incorporated a model of the effect of calcium sensing receptor antagonists on remodeling (Cabal et al. in J Bone Miner Res 28(8):1830-1836, 2013). We have also incorporated a basic model of the effects of vitamin D on calcium homeostasis. We have included a simple model of the mechanism proposed by Bellido et al. (2003), Ross et al. (J Disc Cont Dyn Sys Series B 17(6):2185-2200, 2012), of the

  9. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study.

    PubMed

    Ruiz, Andres D; Daniels, Kelly R

    2014-01-01

    Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy; however, clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking. The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor, mood, and other quality-of-life symptoms in post-menopausal women. This was a prospective, observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1, 2003 and October 1, 2010 in a community pharmacy. Data collection included patient demographics, comorbidities, hormone regimens, and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of-life symptoms as absent, mild, moderate, or severe at baseline, at one to three months follow-up, and three to six months follow-up. Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test. A total of 200 patients met study criteria; 160 received topical bioidentical hormone replacement therapy, and 40 received sublingual bioidentical hormone replacement therapy. Most sublingually-treated patients (70%) received an estrogen combination and 100% received progesterone. Nearly half (43%) of the topically treated patients received an estrogen combination (43%) and 99% received progesterone. The percentage of sublingually treated patients reporting "moderate" or "severe" symptoms was significantly reduced at one to three months follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night sweats (38%, P < 0.01), irritability (36%, P = 0

  10. Identification of plant compounds that disrupt the insect juvenile hormone receptor complex

    PubMed Central

    Lee, Seok-Hee; Oh, Hyun-Woo; Fang, Ying; An, Saes-Byeol; Park, Doo-Sang; Song, Hyuk-Hwan; Oh, Sei-Ryang; Kim, Soo-Young; Kim, Seonghyun; Kim, Namjung; Raikhel, Alexander S.; Je, Yeon Ho; Shin, Sang Woon

    2015-01-01

    Insects impact human health through vector-borne diseases and cause major economic losses by damaging crops and stored agricultural products. Insect-specific growth regulators represent attractive control agents because of their safety to the environment and humans. We identified plant compounds that serve as juvenile hormone antagonists (PJHANs). Using the yeast two-hybrid system transformed with the mosquito JH receptor as a reporter system, we demonstrate that PJHANs affect the JH receptor, methoprene-tolerant (Met), by disrupting its complex with CYCLE or FISC, formation of which is required for mediating JH action. We isolated five diterpene secondary metabolites with JH antagonist activity from two plants: Lindera erythrocarpa and Solidago serotina. They are effective in causing mortality of mosquito larvae at relatively low LD50 values. Topical application of two diterpenes caused reduction in the expression of Met target genes and retardation of follicle development in mosquito ovaries. Hence, the newly discovered PJHANs may lead to development of a new class of safe and effective pesticides. PMID:25624480

  11. Identification of plant compounds that disrupt the insect juvenile hormone receptor complex.

    PubMed

    Lee, Seok-Hee; Oh, Hyun-Woo; Fang, Ying; An, Saes-Byeol; Park, Doo-Sang; Song, Hyuk-Hwan; Oh, Sei-Ryang; Kim, Soo-Young; Kim, Seonghyun; Kim, Namjung; Raikhel, Alexander S; Je, Yeon Ho; Shin, Sang Woon

    2015-02-10

    Insects impact human health through vector-borne diseases and cause major economic losses by damaging crops and stored agricultural products. Insect-specific growth regulators represent attractive control agents because of their safety to the environment and humans. We identified plant compounds that serve as juvenile hormone antagonists (PJHANs). Using the yeast two-hybrid system transformed with the mosquito JH receptor as a reporter system, we demonstrate that PJHANs affect the JH receptor, methoprene-tolerant (Met), by disrupting its complex with CYCLE or FISC, formation of which is required for mediating JH action. We isolated five diterpene secondary metabolites with JH antagonist activity from two plants: Lindera erythrocarpa and Solidago serotina. They are effective in causing mortality of mosquito larvae at relatively low LD50 values. Topical application of two diterpenes caused reduction in the expression of Met target genes and retardation of follicle development in mosquito ovaries. Hence, the newly discovered PJHANs may lead to development of a new class of safe and effective pesticides.

  12. The concept of multiple hormonal dysregulation.

    PubMed

    Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Ferrucci, Luigi; Luci, Michele; Valenti, Giorgio; Ceda, Gianpaolo

    2010-01-01

    Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones that remain stable and anabolic hormones (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Despite the multiple hormonal dysregulation occurring with age, the prevalent line of research in the last decades has tried to explain many age-related phenomena as consequence of one single hormonal derangement with disappointing results. In this review we will list the relationship between hormonal anabolic deficiency and frailty and mortality in older population, providing evidence to the notion that multiple hormonal dysregulation rather than change in single anabolic hormone is a powerful marker of poor health status and mortality.

  13. The molecular site of action of juvenile hormone and juvenile hormone insecticides during metamorphosis: how these compounds kill insects.

    PubMed

    Wilson, Thomas G

    2004-01-01

    Studies in a variety of insects during the past four decades has deepened our understanding of juvenile hormone (JH) physiology, but how this hormone works at the molecular level remains elusive. Similarly, the mechanism of toxicity of JH analogue insecticides is still in question. There is much evidence from laboratory usage that JHAs act as JH agonists and generally show the highest toxicity when applied at the onset of metamorphosis. A physiological basis for the toxicity and morphogenetic effects has been suggested by recent work linking these effects with interference with the expression or action of certain genes, particularly the Broad-Complex (BR-C) transcription factor gene, that direct metamorphic change. Misexpressed BR-C then leads to improper expression of one or more downstream effector genes controlled by BR-C gene products, resulting in abnormal developmental and physiological changes that disrupt metamorphosis. Therefore, JH is a necessary molecule at certain times in insect development but becomes toxic when present during metamorphosis.

  14. Investigation of anabolic steroids in two taste aversion paradigms.

    PubMed

    Ganesan, R; Rosellini, R A; Svare, B

    1993-02-01

    The aversive effects of estradiol have been studied in two different taste aversion paradigms. A similar investigation was undertaken for the anabolic-androgenic steroids, nandralone and testosterone cypionate, using Rockland-Swiss mice. Experiments 1 and 2 used the brief exposure of a novel saccharin solution as the conditioned stimulus for taste aversion learning, and showed that anabolic steroids (1 mg) do not induce taste aversions. Instead, these hormones induced a small non-contingent increase in saccharin preference. Experiment 3 showed that daily nandralone administration (1 mg/day) had a greater anabolic effect than the same dose of testosterone cypionate. Experiment 4 paired the continuous exposure to a novel diet with daily nandralone injections, and showed that steroid treatment increased intake of the novel diet. When the novel diet was subsequently presented with the familiar diet in a two-choice preference test, there was no indication that an aversion was conditioned to the novel target diet. On the contrary, nandralone treatment significantly increased the preference for the novel diet. These experiments show that anabolic-androgenic steroids do not have aversive effects in mice, and that they may have positive consequences.

  15. Canalicular cholestasis induced by anabolic steroids.

    PubMed

    Silva Ruiz, María Del Pilar; Giráldez Gallego, Álvaro; Serrano Jiménez, María

    2017-10-01

    Inappropriate use of anabolic steroids is increasing, usually by younger males in an illicit manner. This is a well-documented case of cholestatic hepatitis attributed to use of anabolic steroids for esthetic and/or athletic purposes.

  16. Anabolic Steroids May Tax the Heart

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_165824.html Anabolic Steroids May Tax the Heart Weight-lifters using ... HealthDay News) -- Long-term use of muscle-building anabolic steroids may take a toll on the heart, ...

  17. Effects of stress hormones on the production of volatile sulfur compounds by periodontopathogenic bacteria.

    PubMed

    Calil, Caroline Morini; Oliveira, Gisele Mattos; Cogo, Karina; Pereira, Antonio Carlos; Marcondes, Fernanda Klein; Groppo, Francisco Carlos

    2014-01-01

    Little is known about the effects of stress hormones on the etiologic agents of halitosis. Thus, the aim of this study was to evaluate in vitro the effects of adrenaline (ADR), noradrenaline (NA) and cortisol (CORT) on bacteria that produce volatile sulfur compounds (VSC), the major gases responsible for bad breath. Cultures of Fusobacterium nucleatum (Fn), Porphyromonas endodontalis (Pe), Prevotella intermedia (Pi) and Porphyromonas gingivalis (Pg) were exposed to 50 µM ADR, NA and CORT or equivalent volumes of sterile water as controls for 12 and 24 h. Growth was evaluated based on absorbance at 660 nm. Portable gas chromatography was used to measure VSC concentrations. Kruskal-Wallis and the Dunn post-hoc test were used to compare the groups. For Fn, ADR, NA and CORT significantly reduced bacterial growth after 12 h and 24 h (p<0.05). All the substances tested increased hydrogen sulfide (H2S) production (p<0.05). For Pe, all the substances tested reduced bacterial development after 24 h (p<0.05), and NA significantly increased the H2S concentration after 12 h (p<0.05). In the Pg and Pi cultures, no effects on bacterial growth were observed (p>0.05). In the Pi cultures, ADR, NA and CORT increased H2S (p<0.05). Catecholamines and cortisol can interfere with growth and H2S production of sub-gingival species in vitro. This process appears to be complex and supports the association between stress and the production of VSC.

  18. Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use.

    PubMed

    L'Hermite, M

    2017-06-01

    Wide rejection of conventional hormone therapy (HT) after the initial publication of the Women's Health Initiative (WHI) led to unjustified use of custom-compounded bioidentical hormones. In the USA, it became an unregulated drug manufacturer industry in disguise, without proper control and making false claims and misleading advertisements. Manufacturing quality is not ensured. Unspecific harm from compounding has occurred on a large scale, such as deaths from infected products and end-stage renal failure plus carcinoma due to confusion between different Chinese herbs. Oral estrogens increase venous thromboembolic and ischemic stroke events, even more when overdosed; these excess risks can be avoided by non-oral administration, readily accessible in custom-compounded HT by administering estradiol through diverse routes (of which transdermal is the best documented). Another risk specific to custom-compounded HT, resulting from estrogen/progestogen imbalance, might be excess endometrial carcinomas. HT can be optimized by continuously combining transdermal estradiol with progesterone (when required). Registered preparations do exist for such a more physiological treatment and therefore must be preferred. Custom compounding is only seldom legitimate, for example in case of allergy (such as to peanut oil) or to prescribe different combinations, doses or components (e.g. estriol, dehydroepiandrosterone or testosterone), even when not approved by local regulatory authorities despite being scientifically acceptable.

  19. Anabolic Steroid Reversal of Denervation Atrophy

    DTIC Science & Technology

    2012-03-01

    10-1-0932 TITLE: Anabolic Steroid Reversal of Denervation Atrophy PRINCIPAL INVESTIGATOR: Dr. Jonathan E. Isaacs...certainly “denervation atrophy” plays a significant role. Anabolic steroids , which have been shown to cause hypertrophy of muscle fibers, increase net...of satellite cells to muscle fibers. In conclusion, there did not seem to be a functional benefit for anabolic steroid treatment following

  20. Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy

    PubMed Central

    Pinkerton, JoAnn V.; Pickar, James H.

    2016-01-01

    Abstract Objective: We review the historical regulation of drug compounding, concerns about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded bioidentical hormone therapies (CBHTs), which do not have proper labeling and warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA) on compounding. Methods: US government websites were searched for documents concerning drug compounding regulation and oversight from 1938 (passage of Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including chronologies, Congressional testimony, FDA guidelines and enforcements, and reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for articles on compounded drugs, including CBHT. Results: Congress explicitly granted the FDA limited oversight of compounded drugs in a 1997 amendment to the FDCA, but the FDA has encountered obstacles in exercising that authority. After 64 patient deaths and 750 adversely affected patients from the 2012 meningitis outbreak due to contaminated compounded steroid injections, Congress passed the DQSA, authorizing the FDA to create a voluntary registration for facilities that manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA regulations for traditional compounding. Given history and current environment, concerns remain about CBHT product regulation and their lack of safety and efficacy data. Conclusions: The DQSA and its reinforcement of §503A of the FDCA solidifies FDA authority to enforce FDCA provisions against compounders of CBHT. The new law may improve compliance and accreditation by the compounding industry; support state and FDA oversight; and prevent the distribution of misbranded, adulterated, or inconsistently compounded medications, and false and misleading claims, thus reducing public health risk. PMID:26418479

  1. Endocrine aspects of anabolic steroids.

    PubMed

    Wu, F C

    1997-07-01

    Understanding of the mechanism of androgen action has been enhanced by advances in knowledge on the molecular basis of activation of the androgen receptor and the importance of tissue conversion of circulating testosterone to dihydrotestosterone and estradiol. New evidence supports the view that supraphysiological doses of anabolic steroids do have a definite, positive effect on muscle size and muscle strength. However, the nature of the anabolic action of androgens on muscle is currently unclear and may involve mechanisms independent of the androgen receptor. The dose-response relationships of anabolic actions vs the potentially serious risk to health of androgenic-anabolic steroids (AAS) use are still unresolved. Most of the adverse effects of AAS are reversible but some are permanent, particularly in women and children. The reported incidence of acute life-threatening events associated with AAS abuse is low, but the actual risk may be underrecognized or underreported; the exact incidence is unknown. The long-term consequences and disease risks of AAS to the sports competitor remain to be properly evaluated.

  2. Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis.

    PubMed

    Jha, Sujeet; Waghdhare, Swati; Reddi, Rajashekar; Bhattacharya, Priyanka

    2012-12-01

    Thyroid storm (TS) is a rare life-threatening condition that is characterized by fever and altered mental status precipitated by endogenous or exogenous critical events, illness/injury, acute iodine load, and thyroid or non thyroid surgery. A large number of thyroid extracts are available and extensively used, even though they are not recommended clinically in hypothyroid or euthyroid patients. Consumption of such products can be dangerous and result in life-threatening TS. Here, we report a case of TS caused by inadvertent intake of very high dosages of triiodothyronine (T3) and thyroxine (T4) in compounded thyroid extracts. Plasmapheresis may be considered an option for the management of exogenous TS. A 62-year-old woman with no significant past medical history presented with severe myalgia, fever, tachycardia, and blood pressure of 170/80 mmHg, which precipitated to an altered mental state within 24 hours. Neurological examination did not reveal any focal deficit or any signs of meningeal irritation. Further investigation revealed that she had been taking thyroid supplements. The patient had accidentally been supplied with a batch of thyroid extract pills that had an inadvertently high content of T4. Her free T3 (FT3) and free T4 (FT4) levels were found to be very high beyond the laboratory readable range (FT3>30 pg/mL; FT4>6.06 ng/dL; thyrotropin [TSH]=0.07 IU/mL). Three days post commencement of standard conservative management of TS, the patient developed posterior reversible encephalopathy syndrome, resulting in a seizure. She remained unresponsive and in a poor mental state. The confirmed exogenous etiology for TS led to a decision to conduct plasmapheresis. Plasmapheresis conducted for two consecutive days proved successful as a therapeutic measure for TS and improved her thyroid profile as well as her mental state. The inappropriate use of thyroid extracts in euthyroid and hypothyroid patients can result in life-threatening TS. Plasmapheresis is probably

  3. Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey.

    PubMed

    Gass, Margery L S; Stuenkel, Cynthia A; Utian, Wulf H; LaCroix, Andrea; Liu, James H; Shifren, Jan L

    2015-12-01

    A national survey was conducted to determine the extent of use of compounded hormone therapy (C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the US Food and Drug Administration (FDA-HT users). This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal or experiencing the menopause transition. The sample was weighted slightly by age, region, education, and race to reflect population attributes based on US Census data. Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT. C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49 years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason for using HT was vasomotor symptoms (∼70%). Nonapproved indications for using HT were selected more often by C-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reported among the 738 FDA-HT users. Significance was not determined because of small numbers. This survey indicates substantial use of C-HT across the country and the possibility of higher rates of endometrial side effects with such products. There is a need for standardized data collection on the extent of use of compounded hormones and their potential risks.

  4. Anabolic treatment with GH, IGF-I, or anabolic steroids in patients with HIV-associated wasting.

    PubMed

    Mulligan, Kathleen; Schambelan, Morris

    2002-09-01

    Wasting, and particularly loss of metabolically active lean tissue, contributes to increased mortality, accelerated disease progression, and impairment of strength and functional status in patients with HIV infection. A variety of protein anabolic agents, including growth hormone, insulin-like growth factor-I, testosterone, nandrolone decanoate, oxandrolone, and oxymetholone, have been studied in patients with HIV-associated wasting. Overall, these studies have demonstrated that treatment with protein anabolic agents can increase lean body mass (LBM) and in some cases provide functional benefits and improvements in quality of life. Further research is needed to determine whether such treatment prolongs survival or reduces the overall health care burden of HIV infection. The advances in identification of successful treatments for HIV-associated wasting can provide a model for using these therapies in other catabolic states, including end-stage renal disease, cancer, chronic obstructive pulmonary disease, and cardiac cachexia.

  5. Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 2.

    PubMed

    Deleruyelle, Laura J

    2016-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provides a brief discussion

  6. Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 3.

    PubMed

    Deleruyelle, Laura J

    2017-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provided a brief discussion

  7. Atrial fibrillation and anabolic steroids.

    PubMed

    Sullivan, M L; Martinez, C M; Gallagher, E J

    1999-01-01

    A young male bodybuilder, consuming large doses of anabolic steroids (AS), presented to the Emergency Department (ED) with symptomatic rapid atrial fibrillation (AF). Echocardiogram revealed significant septal hypokinesis, and posterior and septal wall thickness at the upper limit of normal for highly trained athletes. The atrial fibrillation had not recurred at 10 weeks after discontinuation of AS use. Consumption of these agents in athletes has been associated with hypertension, ischemic heart disease, hypertrophic cardiomyopathy, and sudden death.

  8. HPLC-ICP/MS Analysis of Thyroid Hormone and Related Iodinated Compounds in Tissues and Media

    EPA Science Inventory

    Quantifying thyroid hormone (TH) and the synthetic precursors and metabolic products of TH is important for developing models of the hypothalamic-pituitary-thyroid (HPT) axis as well as for understanding the effects of xenobiotics on HPT axis function. In this study, the developm...

  9. HPLC-ICP/MS Analysis of Thyroid Hormone and Related Iodinated Compounds in Tissues and Media

    EPA Science Inventory

    Quantifying thyroid hormone (TH) and the synthetic precursors and metabolic products of TH is important for developing models of the hypothalamic-pituitary-thyroid (HPT) axis as well as for understanding the effects of xenobiotics on HPT axis function. In this study, the developm...

  10. Anabolic steroids are fool's gold.

    PubMed

    Ryan, A J

    1981-10-01

    Since increases in muscle strength are proportional to increases in the cross-sectional diameter of the muscles being trained, the body must convert greater than normal amounts of amino acids available to it to increase size in athletes in training. When androgens became available in the 1930's they were used primarily to restore positive nitrogen balance in victims of starvation. Anabolic steroids, which were developed to avoid unwanted effects of androgens, were first given to weight lifters, but football players and weight throwers were soon using them. From 1965 to 1977, 25 clinical studies were published dealing with the administration of an anabolic-androgenic steroid to adult human males for evaluating changes in strength and, in 10 of these studies, in maximum oxygen consumption. In 12 of these studies, improvements were claimed from the use of these steroids; in the other 13 no improvements were observed. Other studies have shown that in healthy adult males these steroids reduce testosterone and gonadotrophin output, which reduces spermatogenesis. Alterations of normal liver function have been found in up to 80% of persons treated with C17-alkylated testosterone derivatives. Peliosis hepatitis, with liver failure and death, and fatal liver cancer have also been reported in adults so treated. Reliable methods for detecting anabolic steroids in the urine are now used in certain international competitions. Testing, announced bans, and disqualifications have not been effective in controlling the use of the drugs. The best hope for doing so lies in continuing education of athletes and their supervisors.

  11. Hyperplastic changes and receptor status in the breast tissue of bodybuilders under anabolic-androgenic steroid stimulation.

    PubMed

    Salazar, E L; Torres, J A; Avila, A; Andrade, A

    2000-01-01

    Anabolic androgenic steroids (AAS) are misused by athletes to improve their physical performance. AAS with similar groups and configuration indicate that testosterone is the base of this ability to stimulate anabolic activity. The effect of these compounds on the breast tissue of males that consume them is a confirmation of its metabolic pathway. To confirm its hormonal effects, the status of estradiol and progesterone receptors (ER, PgR) status was determined in cytoplasmic and nuclear fractions (HRc, HRn) of 8 premalignant breast tissues from 8 bodybuilders (aged 21 to 45 years) under AAS stimulation. The control group included 5 males with benign disorders of the breast, but not due to AAS administration. The concentrations of ERc and ERn were significantly higher (p < .05) in males under AAS stimulation than in males without these. The concentrations of PgRc and PgRn do not differ between these two groups (p > .05) The benign breast disease is remarkably similar in female and male patients, suggesting a common origin. In the same way, the measurement of both HRc and HRn is necessary to accurately report receptor concentration.

  12. Anabolic steroids: a review of the literature.

    PubMed

    Haupt, H A; Rovere, G D

    1984-01-01

    The use of anabolic steroids by athletes is controversial. On the one hand, many athletes believe that steroids improve athletic performance and thus provide an advantage to those who use them. On the other hand, the medical and scientific communities believe that inadequate scientific data exist to support the claim that anabolic steroids can improve athletic performance while overwhelming scientific data demonstrate their deleterious effects. Therefore, a large information and credibility gap concerning anabolic steroids exists between the athletes and the medical and scientific communities. We believe that this gap can be closed if both groups are better informed about anabolic steroids. We provide a detailed review of the literature on anabolic steroids that provides to the reader the information needed to make an informed decision on the relative risks and benefits of anabolic steroids to the athlete.

  13. Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an effect-directed analysis of sediment.

    PubMed

    Weiss, Jana M; Andersson, Patrik L; Zhang, Jin; Simon, Eszter; Leonards, Pim E G; Hamers, Timo; Lamoree, Marja H

    2015-07-01

    A variety of anthropogenic compounds has been found to be capable of disrupting the endocrine systems of organisms, in laboratory studies as well as in wildlife. The most widely described endpoint is estrogenicity, but other hormonal disturbances, e.g., thyroid hormone disruption, are gaining more and more attention. Here, we present a review and chemical characterization, using principal component analysis, of organic compounds that have been tested for their capacity to bind competitively to the thyroid hormone transport protein transthyretin (TTR). The database contains 250 individual compounds and technical mixtures, of which 144 compounds are defined as TTR binders. Almost one third of these compounds (n = 52) were even more potent than the natural hormone thyroxine (T4). The database was used as a tool to assist in the identification of thyroid hormone-disrupting compounds (THDCs) in an effect-directed analysis (EDA) study of a sediment sample. Two compounds could be confirmed to contribute to the detected TTR-binding potency in the sediment sample, i.e., triclosan and nonylphenol technical mixture. They constituted less than 1% of the TTR-binding potency of the unfractionated extract. The low rate of explained activity may be attributed to the challenges related to identification of unknown contaminants in combination with the limited knowledge about THDCs in general. This study demonstrates the need for databases containing compound-specific toxicological properties. In the framework of EDA, such a database could be used to assist in the identification and confirmation of causative compounds focusing on thyroid hormone disruption.

  14. Modulation of follistatin and myostatin propeptide by anabolic steroids and gender.

    PubMed

    Mosler, S; Geisler, S; Hengevoss, J; Schiffer, T; Piechotta, M; Adler, M; Diel, P

    2013-07-01

    The purpose of this pilot study was to investigate the impact of training, anabolic steroids and endogenous hormones on myostatin-interacting proteins in order to identify manipulations of myostatin signalling. To identify whether analysis of the myostatin interacting proteins follistatin and myostatin propeptide is suitable to detect the abuse of anabolic steroids, their serum concentrations were monitored in untrained males, bodybuilders using anabolic steroids and natural bodybuilders. In addition, we analysed follistatin and myostatin propeptide serum proteins in females during menstrual cycle. Our results showed increased follistatin concentrations in response to anabolic steroids. Furthermore, variations of sex steroid levels during the menstrual cycle had no impact on the expression of follistatin and myostatin propetide. In addition, we identified gender differences in the basal expression of the investigated proteins. In general, follistatin and myostatin propeptide concentrations were relatively stable within the same individual both in males and females. In conclusion, the current findings provide an insight into gender differences in myostatin-interacting proteins and their regulation in response to anabolic steroids and endogenous hormones. Therefore our data provide new aspects for the development of doping prevention strategies. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Maximizing PTH Anabolic Osteoporosis Therapy. Revision

    DTIC Science & Technology

    2016-09-01

    Bone Anabolism: Engineering a Super Secretory Osteoblast • Invited seminar: 12/11/15: IUPUI Department of Biology Title: Boosting Bone Anabolism... Engineering a Super Secretory Osteoblast • Invited seminar: 01/14/16: IUSM Title: Engineering a Super Secretory Osteoblast • National meeting...American Society for Bone & Mineral Research, September 16-19, 2016, Atlanta, GA, Title: Engineering a hyper-anabolic, super-secreting osteoblast

  16. Regional variability in bed-sediment concentrations of wastewater compounds, hormones and PAHs for portions of coastal New York and New Jersey impacted by hurricane Sandy.

    PubMed

    Phillips, Patrick J; Gibson, Catherine A; Fisher, Shawn C; Fisher, Irene J; Reilly, Timothy J; Smalling, Kelly L; Romanok, Kristin M; Foreman, William T; ReVello, Rhiannon C; Focazio, Michael J; Jones, Daniel K

    2016-06-30

    Bed sediment samples from 79 coastal New York and New Jersey, USA sites were analyzed for 75 compounds including wastewater associated contaminants, PAHs, and other organic compounds to assess the post-Hurricane Sandy distribution of organic contaminants among six regions. These results provide the first assessment of wastewater compounds, hormones, and PAHs in bed sediment for this region. Concentrations of most wastewater contaminants and PAHs were highest in the most developed region (Upper Harbor/Newark Bay, UHNB) and reflected the wastewater inputs to this area. Although the lack of pre-Hurricane Sandy data for most of these compounds make it impossible to assess the effect of the storm on wastewater contaminant concentrations, PAH concentrations in the UHNB region reflect pre-Hurricane Sandy conditions in this region. Lower hormone concentrations than predicted by the total organic carbon relation occurred in UHNB samples, suggesting that hormones are being degraded in the UHNB region. Published by Elsevier Ltd.

  17. Regional variability in bed-sediment concentrations of wastewater compounds, hormones and PAHs for portions of coastal New York and New Jersey impacted by hurricane Sandy

    USGS Publications Warehouse

    Phillips, Patrick; Gibson, Cathy A; Fisher, Shawn C.; Fisher, Irene; Reilly, Timothy J.; Smalling, Kelly L.; Romanok, Kristin M.; Foreman, William T.; ReVello, Rhiannon C.; Focazio, Michael J.; Jones, Daniel K.

    2016-01-01

    Bed sediment samples from 79 coastal New York and New Jersey, USA sites were analyzed for 75 compounds including wastewater associated contaminants, PAHs, and other organic compounds to assess the post-Hurricane Sandy distribution of organic contaminants among six regions. These results provide the first assessment of wastewater compounds, hormones, and PAHs in bed sediment for this region. Concentrations of most wastewater contaminants and PAHs were highest in the most developed region (Upper Harbor/Newark Bay, UHNB) and reflected the wastewater inputs to this area. Although the lack of pre-Hurricane Sandy data for most of these compounds make it impossible to assess the effect of the storm on wastewater contaminant concentrations, PAH concentrations in the UHNB region reflect pre-Hurricane Sandy conditions in this region. Lower hormone concentrations than predicted by the total organic carbon relation occurred in UHNB samples, suggesting that hormones are being degraded in the UHNB region.

  18. [Use and abuse of androgens and anabolic steroids].

    PubMed

    Alén, M

    1993-01-01

    At therapeutic dosages, androgen and anabolic steroids enhance neither muscle strength nor competitive performance. Endogenous androgen secretion is inhibited, and the net effect is negligible. The dosages taken by athletes and body-builders are 10-50 fold greater than the therapeutic dosages, and give rise to hyperandrogenic conditions. Although this improves endurance, strength and muscle development, at the same time a manifest hormone disturbance is developed with a variety of consequences. Abusers, who as a rule inject illicit preparations themselves, are also at risk of hepatitis and HIV.

  19. The effects of dietary boron compounds in supplemented diet on hormonal activity and some biochemical parameters in rats.

    PubMed

    Kucukkurt, Ismail; Akbel, Erten; Karabag, Funda; Ince, Sinan

    2015-03-01

    The aims of this study were to clarify the effects of dietary boric acid or borax, as a boron (B) source, on hormonal status (leptin, insulin, triiodothyronine (T3), and thyroxine) and some biochemical parameter levels as glucose, carnitine, nonesterified fatty acids, and betahydroxybutyric acid in rats. A total of 30 Sprague-Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds especially borax decreased leptin, insulin, and glucose levels, whereas increased T3 and carnitine levels in plasma. In addition, body weight of rats was found to be low in the boric acid group at the end of 4 weeks. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases body weight, leptin, and insulin, whereas increases T3 levels in plasma, so enhances the metabolic activity of rats. Between the B compounds used in this study, it was found that borax had a greater effect on hormonal status than boric acid. © The Author(s) 2012.

  20. Sex steroid and growth hormone supplementation to enhance performance in adolescent athletes.

    PubMed

    Rogol, A D

    2000-08-01

    Ergogenic aids are taken to enhance energy utilization by producing more, controlling its use, or increasing mechanical efficiency. Most athletes are looking toward enhancing performance by proper training modalities and methods; however, some look to the biochemical route for a "quick fix." Thus, the use of chemical agents is on the rise. Herein is provided information on the anabolic-androgenic agents androstenedione, dehydroepiandrosterone, and the "parent" compound, testosterone. The former two, at best, have equivocal activity, but testosterone is both anabolic and androgenic in doses that adolescents might receive. Growth hormone and insulin-like growth factor-1 are anabolic, nonandrogenic compounds with undoubted effects on the lean body mass compartment. Both are expensive, not readily available, and subject to the art of counterfeiting. Thus, very few data are available in non-growth hormone-deficient adolescents. The discussion of these agents ends with issues of fairness, ethics, and the message we attempt to project to our teenagers, whether athletes or not.

  1. Anabolic-androgenic steroids and the adolescent.

    PubMed

    Rogol, A D; Yesalis, C E

    1992-03-01

    This article has reviewed some of the hormonal and behavioral maturation that occurs during adolescence, which are characterized by remarkable physical changes and behavioral vulnerability. Risk taking of many varieties is common and drugs (including anabolic-androgenic steroids) form a part of the prevailing culture in many places. These steroids probably are not severe health hazards when taken intermittently and in low to moderate doses. The 17-alkylated derivatives are clearly the more likely to cause hepatotoxicity. Thus, the scare tactics formerly used (severe constitutional side effects) are doomed to failure. The tenuous link between these drugs and objective behavioral and addictive effects must be strengthened before health strategies based on this issue can be validated. Clearly, the lack of scientific information has impeded, if not precluded, the formulation of an effective health education strategy. The most potent deterrent to the use of steroid drugs by athletes must be the moral issue of fair play and maintaining a "level playing field." We strongly support directed research in these areas and hope that the credibility of the scientific community can be regained after its faulted "stop steroid use" campaigns based on the lack of steroid efficacy in bringing about desired results or on their dire consequences have been replaced with credible evidence to refute their use on these and other grounds.

  2. Illicit Anabolic-Androgenic Steroid Use

    PubMed Central

    Kanayama, Gen; Hudson, James I.; Pope, Harrison G.

    2009-01-01

    The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its derivatives. These substances have been used by elite athletes since the 1950s, but they did not become widespread drugs of abuse in the general population until the 1980s. Thus, knowledge of the medical and behavioral effects of illicit AAS use is still evolving. Surveys suggest that many millions of boys and men, primarily in Western countries, have abused AAS to enhance athletic performance or personal appearance. AAS use among girls and women is much less common. Taken in supraphysiologic doses, AAS show various long-term adverse medical effects, especially cardiovascular toxicity. Behavioral effects of AAS include hypomanic or manic symptoms, sometimes accompanied by aggression or violence, which usually occur while taking AAS, and depressive symptoms occurring during AAS withdrawal. However, these symptoms are idiosyncratic and afflict only a minority of illicit users; the mechanism of these idiosyncratic responses remains unclear. AAS users may also ingest a range of other illicit drugs, including both “body-image” drugs to enhance physical appearance or performance, and classical drugs of abuse. In particular, AAS users appear particularly prone to opioid use. There may well be a biological basis for this association, since both human and animal data suggest that AAS and opioids may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome in a substantial minority of users. AAS dependence may pose a growing public health problem in future years, but remains little studied. PMID:19769977

  3. Anabolic steroids for rehabilitation after hip fracture in older people.

    PubMed

    Farooqi, Vaqas; van den Berg, Maayken E L; Cameron, Ian D; Crotty, Maria

    2014-10-06

    Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture. To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013. Randomised controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture. Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality. We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias, we judged the quality of the evidence for all primary outcomes to

  4. Anabolic steroids for rehabilitation after hip fracture in older people.

    PubMed

    Farooqi, Vaqas; Berg, Maayken E L van den; Cameron, Ian D; Crotty, Maria

    2016-01-01

    Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture. To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013.Selection criteria: Randomized controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture.Data collection and analysis: Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality. We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias

  5. Anabolic steroid accelerated multicompartment syndrome following trauma

    PubMed Central

    Bahia, H; Platt, A; Hart, N; Baguley, P

    2000-01-01

    The case is reported of a 23 year old male body builder who was involved in a road traffic accident after taking anabolic steroids. The resulting trauma caused a severe life threatening acute multicompartment syndrome resulting in the need for urgent multiple fasciotomies. Key Words: anabolic steroids; body builder; trauma; multicompartment syndrome PMID:10953907

  6. Anabolic effects of IGF-1 signaling on the skeleton

    PubMed Central

    Tahimic, Candice G. T.; Wang, Yongmei; Bikle, Daniel D.

    2013-01-01

    This review focuses on the anabolic effects of IGF-1 signaling on the skeleton, emphasizing the requirement for IGF-1 signaling in normal bone formation and remodeling. We first discuss the genomic context, splicing variants, and species conservation of the IGF-1 locus. The modulation of IGF-1 action by growth hormone (GH) is then reviewed while also discussing the current model which takes into account the GH-independent actions of IGF-1. Next, the skeletal phenotypes of IGF-1-deficient animals are described in both embryonic and postnatal stages of development, which include severe dwarfism and an undermineralized skeleton. We then highlight two mechanisms by which IGF-1 exerts its anabolic action on the skeleton. Firstly, the role of IGF-1 signaling in the modulation of anabolic effects of parathyroid hormone (PTH) on bone will be discussed, presenting in vitro and in vivo studies that establish this concept and the proposed underlying molecular mechanisms involving Indian hedgehog (Ihh) and the ephrins. Secondly, the crosstalk of IGF-1 signaling with mechanosensing pathways will be discussed, beginning with the observation that animals subjected to skeletal unloading by hindlimb elevation are unable to mitigate cessation of bone growth despite infusion with IGF-1 and the failure of IGF-1 to activate its receptor in bone marrow stromal cell cultures from unloaded bone. Disrupted crosstalk between IGF-1 signaling and the integrin mechanotransduction pathways is discussed as one of the potential mechanisms for this IGF-1 resistance. Next, emerging paradigms on bone-muscle crosstalk are examined, focusing on the potential role of IGF-1 signaling in modulating such interactions. Finally, we present a future outlook on IGF research. PMID:23382729

  7. Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.

    PubMed

    Schmidt, Azriel; Meissner, Robert S; Gentile, Michael A; Chisamore, Michael J; Opas, Evan E; Scafonas, Angela; Cusick, Tara E; Gambone, Carlo; Pennypacker, Brenda; Hodor, Paul; Perkins, James J; Bai, Chang; Ferraro, Damien; Bettoun, David J; Wilkinson, Hilary A; Alves, Stephen E; Flores, Osvaldo; Ray, William J

    2014-09-01

    Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens.

  8. Steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota—Study design, methods, and data, 2009–10

    USGS Publications Warehouse

    Erickson, Melinda L.

    2012-01-01

    The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota during 2009–10. This report describes the study design and methods, and presents the data collected on steroidal hormones and other related compounds. Environmental and quality-control samples were collected from 40 wells as part of this study. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 16 steroidal hormones and 4 other related compounds, of which all but 2 compounds are endocrine active compounds. Most of the water samples did not contain detectable concentrations of any of the 20 compounds analyzed. Water samples from three wells had detectable concentrations of one or more compounds. Bisphenol A was detected in samples from three wells, and trans-diethylstilbestrol was detected in one of the samples in which bisphenol A also was detected.

  9. Bone biology and anabolic therapies for bone: current status and future prospects.

    PubMed

    Martin, T John

    2014-02-01

    Bone is continuously remodelled at many sites asynchronously throughout the skeleton, with bone formation and resorption balanced at these sites to retain bone structure. Negative balance resulting in bone loss and osteoporosis, with consequent fractures, has mainly been prevented or treated by anti-resorptive drugs that inhibit osteoclast formation and/or activity, with new prospects now of anabolic treatments that restore bone that has been lost. The anabolic effectiveness of parathyroid hormone has been established, and an exciting new prospect is presented of neutralising antibody against the osteocyte protein, sclerostin. The cellular actions of these two anabolic treatments differ, and the mechanisms will need to be kept in mind in devising their best use. On present evidence it seems likely that treatment with either of these anabolic agents will need to be followed by anti-resorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for safe, effective anti-resorptive drugs.

  10. Bone Biology and Anabolic Therapies for Bone: Current Status and Future Prospects

    PubMed Central

    2014-01-01

    Bone is continuously remodelled at many sites asynchronously throughout the skeleton, with bone formation and resorption balanced at these sites to retain bone structure. Negative balance resulting in bone loss and osteoporosis, with consequent fractures, has mainly been prevented or treated by anti-resorptive drugs that inhibit osteoclast formation and/or activity, with new prospects now of anabolic treatments that restore bone that has been lost. The anabolic effectiveness of parathyroid hormone has been established, and an exciting new prospect is presented of neutralising antibody against the osteocyte protein, sclerostin. The cellular actions of these two anabolic treatments differ, and the mechanisms will need to be kept in mind in devising their best use. On present evidence it seems likely that treatment with either of these anabolic agents will need to be followed by anti-resorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for safe, effective anti-resorptive drugs. PMID:24707463

  11. [Influence of anabolic agents on behavior].

    PubMed

    Signoret, J P

    1976-01-01

    Sexual steroids are involved not only in the triggering of sexual activity but also in sex-linked social behaviour (aggressiveness etc.) The use of anabolic agents (particularly steroids) raises the problem of their possible interference with these mechanisms. In the normal male, an injection of androgen does not alter the level of sexual activity, which seems to be determined by nervous mechanisms. On the contrary, by feed-back in the hypothalamo-hypophysial mechanisms it exerts a depressive effect on the endogenous secretion. Female hormones have an inhibiting effect which works both by reducing the actual secretion of androgen and by direct action at two levels: the nervous receptors and the target organs of the genital apparatus. In the female, injections of exogenous hormones may interfere with the mechanisms regulating the oestrous cycle, e.g. inhibition of oestrous and of ovulation by progestagens, and luteotrophic or luteolytic action in the case of the estrogens. In an ovariectomized female the injection of testosterone propionate causes the appearance of sexual receptivity. The behaviour induced in this way is completely normal and free from any abnormal male component. The importance of this action has led to the presumption of a role played by the androgens in the normal triggering off of female sexual behaviour. It therefore seems that the nervous system of the female, but not of the male, possesses a potential bisexuality. The rate at which the hormone passes into the circulation appears to be more important than the actual type of hormone (estrogen or androgen) in causing the appearance in the female of sexual behaviour of one or the other sex. It has been suggested that estrogens might be the active steroid form necessary at the nervous structure level for initiating sexual behaviour in the two sexes, while the androgens would have to undergo aromatization in order to acquire their effectiveness at that level. Aggressiveness depends on the sexual

  12. Organic compounds used in animal husbandry: Chapter 13

    USGS Publications Warehouse

    Wershaw, Robert L.; Shore, Laurence S.; Pruden, Amy; Shore, Laurence S.

    2009-01-01

    Although in general, the same drugs are used by humans as for animal husbandry, some compounds are unique to CAFOs. In raising and fattening steers, anabolic steroids are widely used in the US. In the cattle industry, large use is made of the acaricides, avermectins, and the cypermethrins as well as juvenile growth hormone inhibitor for fly and tick control that could affect soil fauna in very small quantities as they reach the environment without any modification. In poultry, the organic arsenides have been widely used for decades to control coccidiosis and increase growth. The environmental fate of the arsenic excreted in the poultry feces is therefore been an area of concern.

  13. Anabolic steroid abuse and dependence.

    PubMed

    Brower, Kirk J

    2002-10-01

    Anabolic-androgenic steroids (AAS) are mainly used to treat androgen deficiency syndromes and, more recently, catabolic states such as AIDS-associated wasting. There is no evidence in the reviewed literature that AAS abuse or dependence develops from the therapeutic use of AAS. Conversely, 165 instances of AAS dependence have been reported among weightlifters and bodybuilders who, as part of their weight training regimens, chronically administered supraphysiologic doses, often including combinations of injected and oral AAS as well as other drugs of abuse. A new model is proposed in which both the "myoactive" and psychoactive effects of AAS contribute to the development of AAS dependence. The adverse consequences of AAS are reviewed, as well as their assessment by means of a history and physical, mental status examination, and laboratory testing. When patients with AAS use disorders are compared with patients with other substance use disorders, both similarities and differences become apparent and have implications for treatment.

  14. [Regulation of bone mineralization by parathyroid hormone].

    PubMed

    Shimizu, Masaru; Tamura, Tatsuya

    2004-06-01

    In randomized clinical trials, parathyroid hormone (PTH) showed potent anabolic effects on the lumbar spine and decreased the risk of incident vertebral fractures dramatically. Although the anabolic effect of PTH on cortical bone in the femoral neck is still unclear, it should be demonstrated in further clinical studies. Concurrent or sequential therapies of PTH and anti-resorptive agents will be one of the major issues of treatment for osteoporosis in the future.

  15. Occurrence of pharmaceuticals, hormones, and perfluorinated compounds in groundwater in Taiwan.

    PubMed

    Lin, Yen-Ching; Lai, Webber Wei-Po; Tung, Hsin-hsin; Lin, Angela Yu-Chen

    2015-05-01

    In this work, we investigated the emerging pollutants in Taiwanese groundwater for the first time and correlated their presence with possible contamination sources. Fifty target pharmaceuticals and perfluorinated chemicals in groundwater were mostly present at ng L(-1) concentrations, except for 17α-ethynylestradiol, sulfamethoxazole, and acetaminophen (maximums of 1822, 1820, and 1036 ng L(-1), respectively). Perfluorinated compounds were detected with the highest frequencies in groundwater at almost all of the sample sites, especially short-chained perfluorinated carboxylates, which were easily transferred to the groundwater. The results indicate that the compounds found to have high detection frequencies and concentrations in groundwater are similar to those found in other countries around the world. Most common pharmaceuticals that contain hydrophilic groups, such as sulfonamide antibiotics and caffeine, are easily transported through surface waters to groundwater. The results also indicated that the persistent natures of emerging contaminants with high detection frequencies in surface water and groundwater, such as perfluorooctanesulfonate (risk quotient >1), caffeine, and carbamazepine, should be further studied and evaluated.

  16. Anticatabolic and anabolic strategies in critical illness: a review of current treatment modalities.

    PubMed

    Chang, D W; DeSanti, L; Demling, R H

    1998-09-01

    Critically ill patients characteristically exhibit a pronounced catabolism in addition to a down-regulation of normal anabolic activity, leading to major complications from loss of body protein stores. The marked decrease in lean body mass and protein stores leads to the loss of essential structural and functional proteins required for restoring and maintaining homeostasis. The standard management of the catabolic response to injury and illness has centered on optimizing nutrient intake that modulates but does not reverse the process. Complications of ongoing catabolism therefore remain a major cause of morbidity. Addition of anticatabolic and anabolic agents that may counteract "the stress response to injury or illness" may be of significant clinical benefit. Agents currently available for clinical use, which will be described, can be divided into two groups. The first group are nutrients and nutrient metabolites, namely protein and the specific amino acids, glutamine, arginine, and branched chain amino acids, especially leucine. The second group are anabolic hormones, namely growth hormone, testosterone, and the testosterone analog oxandrolone. The pros and cons of these agents, as to their anabolic and anticatabolic value, are described.

  17. Serum concentrations of major perfluorinated compounds among the general population in Korea: dietary sources and potential impact on thyroid hormones.

    PubMed

    Ji, Kyunghee; Kim, Sunmi; Kho, Younglim; Paek, Domyung; Sakong, Joon; Ha, Jongsik; Kim, Sungkyoon; Choi, Kyungho

    2012-09-15

    Perfluorinated compounds (PFCs) have been frequently detected in both the environment and biota, and have become a growing concern. However, information is limited on the potential sources and human health implications of such exposure. We evaluated the exposure levels of 13 major PFCs among a population (n=633, >12 years of age) in a mid-sized city of Korea, and investigated for their potential dietary sources and the impact on thyroid hormone concentrations. For this purpose, we collected blood samples from a general population in Siheung, Korea and measured for 13 PFCs, total thyroxine (T4), and thyroid stimulating hormone (TSH). In addition, a questionnaire survey on diet was conducted. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in relatively greater concentrations than the other 9 PFCs in the blood serum. Males tend to have greater concentrations than females for most PFCs, and the concentrations were elevated as age increased up to 50s. Body mass index (BMI) was also shown to influence the serum concentrations of several PFCs. After adjustment for age, sex, and BMI, the consumption of vegetable, potato, fish/shellfish, and popcorn was identified to be significantly related with concentrations of major PFCs in blood. Among the studied PFCs, the concentrations of perfluorotridecanoic acid (PFTrDA) were negatively correlated with total T4, and positively with TSH levels, especially among females. The result of this study will provide information useful for developing public health and safety management measures for PFCs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Spatial working memory is preserved in rats treated with anabolic-androgenic steroids.

    PubMed

    Smith, S T; Stackman, R W; Clark, A S

    1996-10-21

    The effects of anabolic-androgenic steroid (AAS) compounds on spatial working memory were evaluated in male rats. Thirty days of administration of a high dose of three individual AAS compounds (17 alpha-methyltestosterone, methandrostenolone, or testosterone cypionate) had no effects on spatial memory or motivation as tested on a delayed non-match-to-sample radial arm maze task. Administration of these AAS compounds at doses within the human abuse range does not impair spatial working memory in rats.

  19. [20-Hydroxyecdysone--plant adaptogen: an anabolic effect, possible use in sports nutrition].

    PubMed

    Volodin, V V; Sidorova, Iu S; Mazo, V K

    2013-01-01

    In the review the presentation about plant adaptogens--biologically active compounds is given. Its administration can help to achieve non-specific state of high resistance. The hypothetical mechanism of action: adaptogens are prostressors, reducing excessive increase of stress mediators in the following stress exposure. The features of adaptogenic effect of phytoecdysteroids, polyhydroxylated sterols, which are analogs of hormones of molting and metamorphosis of arthropodas, and are structurally similar to glucocorticoids on the example of the most widely studied phytoecdysteroid--20-hydroxyecdysone--are described. The results of studies of anabolic action of 20-hydroxyecdysone in experiments on laboratory animals and the possible explanation (existing in the modern scientific literature) of the mechanism of this phenomenon are discussed. Scientific publication testifying on the application of phytoecdysteroids to remove chronic fatigue syndrome, reducing nerve and muscle fatigue, improve memory and attention processes are presented. The prospects of using the 20-hydroxyecdysone in the composition of food supplements and specialized products for athletes are discussed.

  20. [New physiological and pharmacological aspects of the growth hormone (I). The effects in adults].

    PubMed

    Díez, J J; Gómez-Pan, A

    1993-04-01

    Growth hormone (GH), a well-known anabolizing agent, not only plays a physiological role in childhood by promoting longitudinal growth, but also it remains to be secreted during adult life. Many aspects on physiological and pharmacological actions of this hormone in adulthood have been clarified in the last years. GH induces the biosynthesis of insulin-like growth factor I (IGF-I), a peptidic compound that acts as a mediator of indirect actions of GH. In GH deficient adults, exogenous GH administration produces a decrease in adipose mass which is accompanied by an increase in lean body mass, mainly due to an enlargement of muscle cell mass. Sodium and water retention has been also described. An augmentation in muscle strength, basal metabolic rate and nitrogen retention by action of GH are expressions of the potential anabolizing effects of this hormone in adult life. Glucose tolerance is decreased by GH, and this effect is accompanied by a decrease in peripheral utilization of glucose and an increase in insulin secretion. GH behaves as a lipolytic hormone and gives rise to an increase in resistance to the lipogenetic action of insulin. GH treatment increases plasma levels of bone Gla protein and other marker of osteoblastic activity, what suggests a physiological role of GH in bone turnover regulation. Many other organic functions are also affected by GH administration.

  1. Anabolic steroid induced hypogonadism in young men.

    PubMed

    Coward, Robert M; Rajanahally, Saneal; Kovac, Jason R; Smith, Ryan P; Pastuszak, Alexander W; Lipshultz, Larry I

    2013-12-01

    The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001). Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis.

    PubMed

    Cosman, Felicia; Nieves, Jeri W; Dempster, David W

    2017-02-01

    The effects of anabolic medications (teriparatide [TPTD] and parathyroid hormone [PTH]) differ in patients who have received recent treatment with potent antiresorptives. This perspective reviews studies evaluating bone density (BMD) and histomorphometric effects of treatment sequences beginning with TPTD/PTH followed by potent antiresorptives and those beginning with potent antiresorptives followed by switching to or adding TPTD. Effect of treatment sequence on spine BMD outcome is minor, with modest quantitative differences. However, when individuals established on potent bisphosphonates are switched to TPTD, hip BMD declines below baseline for at least the first 12 months after the switch to TPTD. This transient hip BMD loss is more prominent when the antiresorptive is denosumab; in this setting, hip BMD remains below baseline for almost a full 24 months. In a controlled comparison of those who switched from alendronate to TPTD versus those who added TPTD to ongoing alendronate, the effect on hip BMD was improved with combination therapy. Furthermore, hip strength improved with the addition of TPTD to ongoing alendronate, whereas it was neutral after switching from alendronate to TPTD, primarily due to the effect on cortical bone. Bone biopsy studies indicate that TPTD stimulates bone formation in patients who have not been treated previously as well as in patients on prior and ongoing bisphosphonates. Histomorphometric evidence suggests that use of alendronate with TPTD blocks the TPTD-induced increase in cortical porosity. When possible, we suggest anabolic therapy first, followed by potent antiresorptive therapy. The common practice of switching to TPTD only after patients have an inadequate response to antiresorptives (intercurrent fracture or inadequate BMD effect) is not the optimal utilization of anabolic treatment. In fact, this may result in transient loss of hip BMD and strength. In this setting, continuing a potent antiresorptive while starting TPTD

  3. [Insulin as an anabolic: hypoglycemia in the bodybuilding world].

    PubMed

    Konrad, C; Schüpfer, G; Wietlisbach, M; Gerber, H

    1998-07-01

    Excessive body building may be dangerous. To promote athletic performance and to improve physical appearance many of the body builders abuse anabolic-androgenic steroids and other drugs. The abuse of insulin as an anabolic medication in this athletic community was followed by a case of severe hypoglycaemia in a body builder. A 30-year old male presented with cerebral symptoms of hypoglycaemia. Directly before an international competition he tried to stimulate muscle growth by using the hypoglycaemic stimulus to the growth hormone. To achieve this he injected 70 IE of a short-acting insulin subcutaneously, resulting in severe hypoglycaemia. After the initial administration of intravenous glucose by the paramedics, he lost consciousness and showed signs of convulsions. After orotracheal intubation by an emergency physician, despite of ongoing infusion of glucose the blood glucose concentration remained low as measured in the out-of-hospital setting. Finally administration of additional glucose and glucagon in the intensive care unit was able to stabilize the metabolic system. In any case of severe hypoglycaemia, repetitive measurements of blood glucose even in the prehospital setting should be performed to detect the hypoglycaemia especially if athletes are concerned.

  4. Prolonged intrahepatic cholestasis and renal failure secondary to anabolic androgenic steroid-enriched dietary supplements.

    PubMed

    Krishnan, Prashant V; Feng, Zhen-Zhou; Gordon, Stuart C

    2009-08-01

    The illegal enrichment of anabolic androgenic steroids in over-the-counter dietary supplements is well documented, but the health consequences have not been widely recognized. Three recent reports document cholestatic jaundice and nephropathy due to these compounds. We present 3 additional cases of anabolic androgenic steroid-enriched dietary supplement-induced hepatotoxicity and 1 case of renal failure, and we review the literature and the relevant features of this growing health concern. Recognition of this entity could obviate the need for invasive diagnostic testing and hospitalization and facilitate diagnosis and appropriate counseling.

  5. Anabolic-androgenic steroid and adrenal steroid effects on hippocampal plasticity.

    PubMed

    Clark, A S; Mitre, M C; Brinck-Johnsen, T

    1995-05-08

    Anabolic-androgenic steroids (AAS) are synthetic androgen-like compounds which are taken in high doses by athletes with the intention of enhancing muscular appearance, strength and/or athletic performance. Recent research indicates that high doses of AAS may influence the functions of the hippocampus. This evidence led us to explore the extent to which chronic AAS treatments influence spatial memory and the integrity of the hippocampus in the rat. Gonadally intact adult male Long-Evans rats were treated with either the AAS methandrostenolone, a steroid 'cocktail' (TNB; testosterone cypionate, boldenone undecylenate and nandrolone decanoate), or the oil vehicle daily for 12 weeks. A group of male rats treated with corticosterone (CORT; 10 mg/day) was also examined. Spatial memory was assessed in the Morris water maze after 10 weeks of hormone treatment. At 12 weeks, the animals were sacrificed, blood collected and the brain sectioned to assess hippocampal cell number. There were no impairments in the acquisition or retention of the Morris water maze in any hormone treatment group. Although serum testosterone levels were elevated in rats treated with TNB relative to the oil controls, neither the TNB or methandrostenolone treatments produced changes in hippocampal cell number. Serum CORT levels were significantly elevated in the rats treated with CORT and cell loss (15%) was detectable in the CA3b subfield in this group of animals. These results indicate that the AAS administered in the present study were not detrimental to hippocampal spatial memory or cell survival and that, while chronic CORT may produce mild hippocampal cell loss, this loss is not accompanied by deficits on a spatial memory task.

  6. The anabolic steroid methandienone targets the hypothalamic-pituitary-testicular axis and myostatin signaling in a rat training model.

    PubMed

    Mosler, Stephanie; Pankratz, Carlos; Seyfried, Alexis; Piechotta, Marion; Diel, Patrick

    2012-01-01

    There is increasing evidence that the biological activity of myostatin (MSTN), a negative regulator of muscle growth, is affected by training but also anabolic steroids. In this study, we analyzed the effects of the frequently abused anabolic steroid methandienone (Md) on the hypothalamic-pituitary-testicular axis and androgen-sensitive tissues in intact rats performing a treadmill training to simulate the situation of abusing athletes. The anabolic effects were correlated with the expression of members of the MSTN signaling cascade. Md treatment resulted in a significant stimulation of anabolic activity of the levator ani muscle, which was further increased by training, while prostate and seminal vesicle weights decreased in conformance with hormone concentrations of LH and testosterone. In gastrocnemius muscle, mRNA expression of genes of the MSTN signaling cascade (MSTN, Smad7 and MyoD) was reduced by training but not after Md treatment, in soleus muscle MSTN and its inhibitors, follistatin (FLST) and Smad-7 were only affected after training in combination with Md treatment. In summary, our data demonstrate that Md treatment of intact rats results in anabolic effects which are enhanced in combination with physical activity. Interestingly, the anabolic activity on the levator ani was increased in combination with training, although the levator ani muscle was not specifically stimulated by our training protocol. In the m. gastrocnemius and soleus, the anabolic effects correlate with changes in the expression patterns of genes involved in MSTN signaling. Our data provide evidence that the decrease in the weight of androgen-sensitive sexual glands, observed after Md treatment, is caused by a suppression of endogenous testosterone synthesis. These observations provide new insights into the molecular mechanisms of the interaction between anabolic steroids, training and MSTN signaling during skeletal muscle adaptation.

  7. Chronic Drought Decreases Anabolic and Catabolic BVOC Emissions of Quercus pubescens in a Mediterranean Forest

    PubMed Central

    Saunier, Amélie; Ormeño, Elena; Wortham, Henri; Temime-Roussel, Brice; Lecareux, Caroline; Boissard, Christophe; Fernandez, Catherine

    2017-01-01

    Biogenic volatile organic compounds (BVOC) emitted by plants can originate from both anabolism (metabolite production through anabolic processes) and catabolism (metabolite degradation by oxidative reactions). Drought can favor leaf oxidation by increasing the oxidative pressure in plant cells. Thus, under the precipitation decline predicted for the Mediterranean region, it can be expected both strong oxidation of anabolic BVOC within leaves and, as a result, enhanced catabolic BVOC emissions. Using an experimental rain exclusion device in a natural forest, we compared the seasonal course of the emissions of the main anabolic BVOC released by Q. pubescens (isoprene and methanol) and their catabolic products (MACR+MVK+ISOPOOH and formaldehyde, respectively) after 3 years of precipitation restriction (−30% of rain). Thus, we assume that this repetitive amplified drought promoted a chronic drought. BVOC emissions were monitored, on-line, with a PTR-ToF-MS. Amplified drought decreased all BVOC emissions rates in spring and summer by around 40–50 %, especially through stomatal closure, with no effect in autumn. Moreover, ratios between catabolic and anabolic BVOC remained unchanged with amplified drought, suggesting a relative stable oxidative pressure in Q. pubescens under the water stress applied. Moreover, these results suggest a quite good resilience of this species under the most severe climate change scenario in the Mediterranean region. PMID:28228762

  8. Direct determination of anabolic steroids in pig urine by a new SPME-GC-MS method.

    PubMed

    Zhang, Zhuomin; Duan, Hongbin; Zhang, Lan; Chen, Xi; Liu, Wei; Chen, Guonan

    2009-05-15

    A new solid phase microextraction (SPME) method coupled with gas chromatography-mass spectrometry (GC-MS) was developed for rapid determination of four anabolic steroids such as 3alpha-hydroxy-5alpha-androstane-17-one (HA), dihydrotestosterone (DHT), androstenedione (AD) and methyltestosterone (MT) in pig urine. SPME was used to extract the four anabolic compounds directly without derivatization. The optimum SPME sampling conditions were based on the home-made carbowax-divinylbenzene (CW-DVB) fiber coating during extraction at 40 degrees C for 50 min with 0.18 g/mL NaCl solution and 750 rpm stirring speed. The linear ranges of the proposed method were in the range of 8-640 pg/mL for HA and DHT and 16-510 pg/mL for AD and MT, respectively. The detection limits (S/N=3) were from 2 to 8 pg/mL for the four anabolic steroids. This SPME method provided very high enrichment factors for the four anabolic steroids, which were 1063-fold and 965-fold for HA and DHT at the concentration of 8 pg/mL and 207-fold and 451-fold for AD and MT at the concentration of 16 pg/mL, respectively. The recoveries ranged from 71.3 to 121%, and the RSDs were lower than 12.9%. The method was sensitive and reliable for determination of trace anabolic steroids in biological samples.

  9. THE MECHANISM OF ACTION OF 17-HYDROXY-11-DEHYDROCORTICOSTERONE (COMPOUND E) AND OF THE ADRENOCORTICOTROPIC HORMONE IN EXPERIMENTAL HYPERSENSITIVITY IN RABBITS

    PubMed Central

    Germuth, Frederick G.; Oyama, Jiro; Ottinger, Barbara

    1951-01-01

    The concurrent administration of compound E at a daily dosage of 2 mg. per kg. to rabbits receiving daily intracutaneous injections of crystalline egg albumin markedly inhibited the development of anaphylactic hypersensitivity of the Arthus type. ACTH, when given at a similar dosage, produced a much less marked effect. Both hormones suppressed circulating antibody and as with the Arthus reaction, the suppression produced by compound E was much greater than that obtained with ACTH. When treatment with compound E was started following sensitization, there was a rapid decline in circulating antibody and, if the pretreatment serum antibody was low, there was also a progressive decrease in skin reactivity, becoming negative after 5 days of treatment. When the pretreatment serum antibody concentration was great, so that by the termination of treatment the antibody concentration was still above the level ordinarily sufficient for a maximal skin response, the Arthus reaction was unaffected by treatment. These considerations as well as the failure of compound E to inhibit the systemic passive Arthus reaction suggest that the inhibitory effect of compound E and ACTH on the development of experimental hypersensitivity results from the hormonal reduction of circulating antibody. Treatment with compound E had no effect on the rate of disappearance of circulating antibody in the passively immunized rabbit. This finding suggests that ACTH and compound E reduce circulating antibody by inhibiting antibody formation rather than by promoting antibody destruction. The question is raised as to whether the marked lymphoid atrophy produced by these hormones may be related to the interference with antibody production. PMID:14861375

  10. Why women choose compounded bioidentical hormone therapy: lessons from a qualitative study of menopausal decision-making.

    PubMed

    Thompson, Jennifer Jo; Ritenbaugh, Cheryl; Nichter, Mark

    2017-10-02

    In recent years, compounded bioidentical hormone therapy (CBHT) has emerged as a popular alternative to manufactured, FDA approved hormone therapy (HT)-despite concerns within the medical community and the availability of new FDA approved "bioidentical" products. This study aims to characterize the motivations for using CBHT in a U.S. sample of ordinary midlife women. We analyze data collected from 21 current and former users of CBHT who participated in a larger qualitative study of menopausal decision-making among U.S. women. Interviews and focus groups were audio-recorded, transcribed verbatim, and analyzed thematically using an iterative inductive and deductive process. Although women's individual motivations varied, two overarching themes emerged: "push motivations" that drove women away from conventional HT and from alternative therapies, and "pull motivations" that attracted women to CBHT. Push motivations focused on (1) fear and uncertainty about the safety of conventional HT, (2) an aversion to conjugated estrogens in particular, and (3) and overarching distrust of a medical system perceived as dismissive of their concerns and overly reliant on pharmaceuticals. Participants also voiced dissatisfaction with the effectiveness of herbal and soy supplements. Participants were attracted to CBHT because they perceive it to be (1) effective in managing menopausal symptoms, (2) safer than conventional HT, (3) tailored to their individual bodies and needs, and (4) accompanied by enhanced clinical care and attention. This study finds that women draw upon a range of "push" and "pull" motivations in their decision to use CBHT. Importantly, we find that women are not only seeking alternatives to conventional pharmaceuticals, but alternatives to conventional care where their menopausal experience is solicited, their treatment goals are heard, and they are engaged as agents in managing their own menopause. The significance of this finding goes beyond understanding why

  11. [Anabolic action of PTH under the loading/unloading condition].

    PubMed

    Sakai, Akinori

    2012-03-01

    Parathyroid hormone (PTH) is available for the treatment of osteoporosis in Japan. PTH is administered subcutaneously daily or weekly. According to the results of animal experiments, the anabolic action of PTH on bone depends on dosage, condition of loading, and region of bone. Administration of PTH preserved trabecular bone formation rate reduced by immobilization or unloading at the same level of that under the normal mobilization or loading condition, but at low dose did not preserve periosteal bone formation rate reduced by unloading. PTH at high dose (40μg/kg BW) completely preserved trabecular bone volume reduced by immobilization in mice. Thus, we consider that PTH could be clinically effective for immobilization- and/or unloading-induced bone loss.

  12. Effects of androgenic-anabolic steroids in athletes.

    PubMed

    Hartgens, Fred; Kuipers, Harm

    2004-01-01

    Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. They can exert strong effects on the human body that may be beneficial for athletic performance. A review of the literature revealed that most laboratory studies did not investigate the actual doses of AAS currently abused in the field. Therefore, those studies may not reflect the actual (adverse) effects of steroids. The available scientific literature describes that short-term administration of these drugs by athletes can increase strength and bodyweight. Strength gains of about 5-20% of the initial strength and increments of 2-5 kg bodyweight, that may be attributed to an increase of the lean body mass, have been observed. A reduction of fat mass does not seem to occur. Although AAS administration may affect erythropoiesis and blood haemoglobin concentrations, no effect on endurance performance was observed. Little data about the effects of AAS on metabolic responses during exercise training and recovery are available and, therefore, do not allow firm conclusions. The main untoward effects of short- and long-term AAS abuse that male athletes most often self-report are an increase in sexual drive, the occurrence of acne vulgaris, increased body hair and increment of aggressive behaviour. AAS administration will disturb the regular endogenous production of testosterone and gonadotrophins that may persist for months after drug withdrawal. Cardiovascular risk factors may undergo deleterious alterations, including elevation of blood pressure and depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol levels. In echocardiographic studies in male athletes, AAS did not seem to affect cardiac structure and function, although in animal studies these drugs have been observed to exert hazardous effects on heart structure and function. In studies of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to be strongly affected by AAS

  13. Anabolic steroids and cardiovascular risk.

    PubMed

    Angell, Peter; Chester, Neil; Green, Danny; Somauroo, John; Whyte, Greg; George, Keith

    2012-02-01

    Recent reports from needle exchange programmes and other public health initiatives have suggested growing use of anabolic steroids (AS) in the UK and other countries. Data indicate that AS use is not confined to body-builders or high-level sportsmen. Use has spread to professionals working in emergency services, casual fitness enthusiasts and subelite sportsmen and women. Although the precise health consequences of AS use is largely undefined, AS use represents a growing public health concern. Data regarding the consequences of AS use on cardiovascular health are limited to case studies and a modest number of small cohort studies. Numerous case studies have linked AS use with a variety of cardiovascular disease (CVD) events or endpoints, including myocardial infarction, stroke and death. Large-scale epidemiological studies to support these links are absent. Consequently, the impact of AS use upon known CVD risk factors has been studied in relatively small, case-series studies. Data relating AS use to elevated blood pressure, altered lipid profiles and ECG abnormalities have been reported, but are often limited in scope, and other studies have often produced equivocal outcomes. The use of AS has been linked to the appearance of concentric left ventricular hypertrophy as well as endothelial dysfunction but the data again remains controversial. The mechanisms responsible for the negative effect of AS on cardiovascular health are poorly understood, especially in humans. Possibilities include direct effects on myocytes and endothelial cells, reduced intracellular Ca2+ levels, increased release of apoptogenic factors, as well as increased collagen crosslinks between myocytes. New data relating AS use to cardiovascular health risks are emerging, as novel technologies are developed (especially in non-invasive imaging) that can assess physiological structure and function. Continued efforts to fully document the cardiovascular health consequences of AS use is important to

  14. Simultaneous determination of selected hormones, endocrine disruptor compounds, and pesticides in water medium at trace levels by GC-MS after dispersive liquid-liquid microextraction.

    PubMed

    Chormey, Dotse Selali; Büyükpınar, Çağdaş; Turak, Fatma; Komesli, Okan Tarık; Bakırdere, Sezgin

    2017-06-01

    The need to enhance food safety has led to major advancements in pesticide productions, and though many benefits have been gained, environmental contamination has also risen from these chemicals that tend to persist in the environment. Some pesticides, together with other chemicals commonly called endocrine disruptor compounds, block the receptor sites of hormones or mimic displaced hormones, leading to imbalanced hormonal levels that result in health disorders and diseases. These chemicals occur at trace levels and are not directly detected by conventional analytical methods. A dispersive liquid-liquid microextraction method was therefore developed for preconcentration of 12 analytes including hormones, endocrine disruptor compounds, and pesticides, to be analyzed by gas chromatography mass spectrometry. This was achieved by optimizing parameters such as extractor solvent type and amount, dispersive solvent type and amount, pH, and salt effect that affect extraction output. The limits of detection and quantification of the developed method were between 0.09 and 3.36 and 0.31 and 11.19 ng mL(-1), respectively. The calibration plots of the analytes also showed good linearity and low percent relative standard deviations. Recovery studies were performed for tap water and wastewater samples, and the percent recoveries recorded were between 84 and 109%.

  15. Short Anabolic Peptides for Bone Growth.

    PubMed

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. © 2016 Wiley Periodicals, Inc.

  16. Doping in sport and exercise: anabolic, ergogenic, health and clinical issues.

    PubMed

    Bird, Stephen R; Goebel, Catrin; Burke, Louise M; Greaves, Ronda F

    2016-03-01

    The use of doping agents is evident within competitive sport in senior and junior age groups, where they are taken by non-elite as well as elite participants. They are also taken in non-sporting contexts by individuals seeking to 'improve' their physique through an increase in muscle and/or decrease in fat mass. While attaining accurate data on the prevalence of their use has limitations, studies suggest the illicit use of doping agents by athletes and non-athletes may be 1-5% in the population and greater than 50% in some groups; with the prevalence being higher in males. There is conclusive evidence that some doping agents are anabolic and ergogenic. There is also evidence that the use of doping agents such as anabolic androgenic steroids, growth hormone and other anabolic agents, erythropoietin and stimulants conveys considerable health risks that include, but are not limited to: cardiovascular disease, diabetes, cancer, mental health issues, virilisation in females and the suppression of naturally produced androgens in males. This review will outline the anabolic, ergogenic and health impacts of selected doping agents and methods that may be used in both the sporting and physique development contexts. It also provides a brief tabulated overview of the history of doping and how doping agents may impact upon the analyses of clinical samples.

  17. Metabolic Response to Injury and Role of Anabolic Hormones

    DTIC Science & Technology

    2007-01-01

    periphery to the liver with inefficient transport back to the periphery; feeding with carbohydrate or fat with de-novo synthesis of fat plays only a very...two-fold after severe burn [30]. The principal defect is an accel- erated rate of protein breakdown with a failure of com- pensatory synthesis ...resulting in a decrease in net protein synthesis (muscle protein synthesis minus muscle protein breakdown) [31]. Hyperpyrexia Burn patients have an elevated

  18. Hormonal growth promoting agents in food producing animals.

    PubMed

    Stephany, Rainer W

    2010-01-01

    In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters ("anabolics") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters ("hormones") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of "legal natural levels" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone

  19. Anabolic steroids: implications for the nurse practitioner.

    PubMed

    Duncan, D J; Shaw, E B

    1985-12-01

    Anabolic steroids are being used by athletes in a wide variety of sports in efforts to enhance their athletic performances. Steroid abuse is complex to evaluate due to the highly emotional subject matter and the limitations in researching anabolic steroids. This article has been written to heighten the practitioner's awareness of the problem of "sports doping" with anabolic steroids. It will provide practical information on possible consequences of steroid use and outline essential information to obtain through the history, physical exam and laboratory studies. Intervention strategies based on the three levels of prevention are described. With awareness of the problem of sports doping and knowledge of how to deal with it in primary care, the nurse practitioner can enhance the health care provided to aspiring athletes, athletes and retired athletes.

  20. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids

    PubMed Central

    Martínez-Rivera, Freddyson J.; Pérez-Laspiur, Juliana; Santiago-Gascot, María E.; Alemán-Reyes, Abner G.; García-Santiago, Emanuel; Rodríguez-Pérez, Yolanda; Calo-Guadalupe, Cristhian; Otero-Pagán, Inelia; Ayala-Pagán, Roxsana N.; Martínez, Magdiel; Cantres-Rosario, Yisel M.; Meléndez, Loyda M.; Barreto-Estrada, Jennifer L.

    2017-01-01

    The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH). In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM). These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE) and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function. PMID:28719635

  1. Review of Androgenic Anabolic Steroid Use

    SciTech Connect

    T. Borges; G. Eisele; C. Byrd

    2001-07-31

    An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition or they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).

  2. Preventing Anabolic Steroid Use: Guidelines and Activities.

    ERIC Educational Resources Information Center

    Nutter, June; Rauhe, Betty

    1997-01-01

    Information about anabolic steroids should be included in the school health curriculum as early as possible. The paper presents suggestions for planning education programs and offers a variety of activities and strategies appropriate for many age groups, including case studies, story completion, posters, demonstrations, projects, creative writing,…

  3. Preventing Anabolic Steroid Use: Guidelines and Activities.

    ERIC Educational Resources Information Center

    Nutter, June; Rauhe, Betty

    1997-01-01

    Information about anabolic steroids should be included in the school health curriculum as early as possible. The paper presents suggestions for planning education programs and offers a variety of activities and strategies appropriate for many age groups, including case studies, story completion, posters, demonstrations, projects, creative writing,…

  4. Anabolic androgenic steroid-induced Takotsubo cardiomyopathy

    PubMed Central

    Sella, Gianluigi; Bellanti, Giancarlo; Margheri, Massimo

    2015-01-01

    Anabolic steroid abuse, aimed at increasing muscle mass, has been growing in recent years. We describe a case of a 25-year-old bodybuilder who, after taking nandrolone and stanozolol, presented with Takotsubo syndrome. The angiography showed a normal coronary anatomy with the absence of stenosis. The left ventricular function was completely normalised after 1 week. PMID:25804946

  5. Androgenic anabolic steroids also impair right ventricular function.

    PubMed

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  6. Biochemistry and physiology of anabolic androgenic steroids doping.

    PubMed

    Lippi, G; Franchini, M; Banfi, G

    2011-05-01

    Anabolic Androgenic Steroids (AASs) are chemical and pharmacological derivatives of the male hormone testosterone which are widely used for increasing burst and sprinting activities in sports. Although AASs are thought to be transversal to the plurality of sports disciplines, they are principally misused by bodybuilders, weightlifters, shot, hammer, discus or javelin throwers, rugby and American football players as well as by swimmers and runners. AAS exert a kaleidoscope of effects on human biology, principally through the 5-α-reductase-mediated conversion into dihydrotestosterone, the aromatase-mediated conversion into female sex hormones, a competitive antagonism to the glucocorticoid receptors, the potential stimulation of erythropoietin secretion as well as psychoactive effects on the brain. The influence of AASs on physical performance is still undefined, since the large number of studies published so far have described discordant and often contradictory outcomes. Nevertheless, animal and human investigations support the hypothesis that the administration of AASs might increase lean body mass, muscle mass, and maximal voluntary strength especially in men, so that they would represent an appealing form of doping for increasing power capacity, sustaining intensive training periods and, last but not least, as a cosmetic muscle makeover. The aim of this article is to review the biochemistry, physiology and the ergogenic effects of AASs.

  7. Anabolic and antiresorptive therapy for osteoporosis: combination and sequential approaches.

    PubMed

    Cosman, Felicia

    2014-12-01

    In the recent Bone Key Reports review, it was noted that combinations of anabolic and antiresorptive agents have potential to improve bone density and bone strength more than either agent as monotherapy. Small clinical trials have been performed evaluating combinations of PTH1-34 (TPTD) or PTH1-84 (PTH) with a variety of antiresorptives including hormone/estrogen therapy, raloxifene, alendronate, risedronate, ibandronate, zoledronic acid, and denosumab. Most of the studies evaluate dual-energy X-ray absorptiometry outcomes, and a few trials report volumetric mineral density (BMD) by quantitative computed tomography, followed by finite element modeling to calculate bone strength. None of the studies has been powered to assess differences in fracture incidence between combination therapy and monotherapy. BMD outcomes vary based on the timing of introduction of the anabolic agent (before, during, or after antiresorptive treatment), as well as the specific anabolic and antiresorptive used. Furthermore, effects of combination therapies are site-dependent. The most consistent effect of combining antiresorptive agents with PTH or TPTD is a superior hip BMD outcome compared with TPTD/PTH alone. This is most evident when TPTD/PTH is combined with a bisphosphonate or denosumab. In contrast to findings in the hip, in the majority of studies, there is no benefit to spine BMD with combination therapy vs monotherapy. The 2 exceptions to this are when TPTD is combined with denosumab and when TPTD is given as monotherapy first for 9 months, followed by the addition of alendronate (with continuation administration of TPTD). Based on what we now know, in patients previously treated with bisphosphonates who suffer hip fractures or who have very low or declining hip BMD, strong consideration should be given to starting TPTD and continuing a potent antiresorptive agent (possibly switching to zoledronic acid or denosumab) to improve hip BMD and strength quickly. Furthermore, in

  8. Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis.

    PubMed

    Hanada, Keigo; Furuya, Kazuyuki; Yamamoto, Noriko; Nejishima, Hiroaki; Ichikawa, Kiyonoshin; Nakamura, Tsutomu; Miyakawa, Motonori; Amano, Seiji; Sumita, Yuji; Oguro, Nao

    2003-11-01

    A novel nonsteroidal androgen receptor (AR) binder, S-40503, was successfully generated in order to develop selective androgen receptor modulators (SARMs). We evaluated the binding specificity for nuclear receptors (NRs) and osteoanabolic activities of S-40503 in comparison with a natural nonaromatizable steroid, 5alpha-dihydrotestosterone (DHT). The compound preferentially bound to AR with nanomolar affinity among NRs. When S-40503 was administrated into orchiectomized (ORX) rats for 4 weeks, bone mineral density (BMD) of femur and muscle weight of levator ani were increased as markedly as DHT, but prostate weight was not elevated over the normal at any doses tested. In contrast, DHT administration caused about 1.5-fold increase in prostate weight. The reduced virilizing activity was clearly evident from the result that 4-week treatment of normal rats with S-40503 showed no enlargement of prostate. To confirm the bone anabolic effect, S-40503 was given to ovariectomized (OVX) rats for 2 months. The compound significantly increased the BMD and biomechanical strength of femoral cortical bone, whereas estrogen, anti-bone resorptive hormone, did not. The increase in periosteal mineral apposition rate (MAR) of the femur revealed direct bone formation activity of S-40503. It was unlikely that the osteoanabolic effect of the compound was attribute to the enhancement of muscle mass, because immobilized ORX rats treated with S-40503 showed a marked increase in BMD of tibial cortical bone without any actions on the surrounding muscle tissue. Collectively, our novel compound served as a prototype for SARMs, which had unique tissue selectivity with high potency for bone formation and lower impact upon sex accessory tissues.

  9. Plant ecdysteroids: plant sterols with intriguing distributions, biological effects and relations to plant hormones.

    PubMed

    Tarkowská, Danuše; Strnad, Miroslav

    2016-09-01

    The present review summarises current knowledge of phytoecdysteroids' biosynthesis, distribution within plants, biological importance and relations to plant hormones. Plant ecdysteroids (phytoecdysteroids) are natural polyhydroxylated compounds that have a four-ringed skeleton, usually composed of either 27 carbon atoms or 28-29 carbon atoms (biosynthetically derived from cholesterol or other plant sterols, respectively). Their physiological roles in plants have not yet been confirmed and their occurrence is not universal. Nevertheless, they are present at high concentrations in various plant species, including commonly consumed vegetables, and have a broad spectrum of pharmacological and medicinal properties in mammals, including hepatoprotective and hypoglycaemic effects, and anabolic effects on skeletal muscle, without androgenic side-effects. Furthermore, phytoecdysteroids can enhance stress resistance by promoting vitality and enhancing physical performance; thus, they are considered adaptogens. This review summarises current knowledge of phytoecdysteroids' biosynthesis, distribution within plants, biological importance and relations to plant hormones.

  10. Growth hormone therapy in progeria.

    PubMed

    Sadeghi-Nejad, Ab; Demmer, Laurie

    2007-05-01

    Catabolic processes seen in Hutchinson-Gilford progeria resemble those of normal aging and, in the affected children, usually result in death at an early age. In addition to its growth promoting effects, growth hormone (GH) has potent anabolic properties. Administration of GH ameliorates some of the catabolic effects of normal aging. We report the results of GH treatment in a young child with progeria.

  11. When color fails: illicit blue tablets containing anabolic androgen steroids.

    PubMed

    Favretto, Donata; Castagna, Franca; Maietti, Sergio; Boscolo-Berto, Rafael; Ferrara, Santo Davide

    2013-09-01

    The necessity of specific, confirmatory tests in the identification of seized illicit products was highlighted by the analysis of eighteen heart shaped, blue tablets confiscated by Police at a street control in the North East of Italy. The tablets responded as amphetamines to a preliminary color test (Marquis); a subsequent, confirmatory assay by gas chromatography-mass spectrometry revealed the presence of two anabolic androgen steroids (AAS), methandienone and methyltestosterone, in concentration of 1.7 and 1.5mg respectively per tablet; no trace of amphetamine-like or nitrogen containing compounds was found. The observed orange coloration was due to the reaction of concentrated sulphuric acid, contained in the Marquis reagent, with the Δ(4) C-3 keto group of steroids. The two AAS, banned under the world antidoping code, are not considered as psychoactive drugs of abuse in most countries, although their trafficking may entangle severe public health concerns.

  12. The hormonal pathway to cognitive impairment in older men.

    PubMed

    Maggio, M; Dall'Aglio, E; Lauretani, F; Cattabiani, C; Ceresini, G; Caffarra, P; Valenti, G; Volpi, R; Vignali, A; Schiavi, G; Ceda, G P

    2012-01-01

    In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline. Decline in cognitive function, typically memory, is a major symptom of dementia. The "preclinical phase" of cognitive impairment occurs many years before the onset of dementia. The identification of relevant modifiable factors, including the hormonal dysregulation, may lead to therapeutic strategies for preventing the cognitive dysfunction. There are several mechanisms by which anabolic hormones play a role in neuroprotection and neuromodulation. These hormones facilitate recovery after brain injury and attenuate the neuronal loss. In contrast, elevated thyroid hormones may increase oxidative stress and apoptosis, leading to neuronal damage or death. In this mini review we will address the relationship between low levels of anabolic hormones, changes in thyroid hormones and cognitive function in older men. Then, giving the contradictory data of the literature and the multi-factorial origin of dementia, we will introduce the hypothesis of multiple hormonal derangement as a better determinant of cognitive decline in older men.

  13. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

    PubMed Central

    2014-01-01

    Background Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. Methods Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. Results The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement

  14. Growth Hormone and Craniofacial Tissues. An update

    PubMed Central

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

  15. Bioidentical Hormones and Menopause

    MedlinePlus

    ... made products. These are made in a compounding pharmacy (a pharmacy that mixes medications according to a doctor’s instructions). ... that bioidentical hormones, whether prepared by a compounding pharmacy or pharmaceutical company, are safer to use than ...

  16. Multiple Hormonal Dysregulation as Determinant of Low Physical Performance and Mobility in Older Persons

    PubMed Central

    Maggio, Marcello; Lauretani, Fulvio; De Vita, Francesca; Basaria, Shehzad; Lippi, Giuseppe; Buttò, Valeria; Luci, Michele; Cattabiani, Chiara; Ceresini, Graziano; Verzicco, Ignazio; Ferrucci, Luigi; Ceda, Gian Paolo

    2015-01-01

    Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals. PMID:24050169

  17. Multiple hormonal dysregulation as determinant of low physical performance and mobility in older persons.

    PubMed

    Maggio, Marcello; Lauretani, Fulvio; De Vita, Francesca; Basaria, Shehzad; Lippi, Giuseppe; Butto, Valeria; Luci, Michele; Cattabiani, Chiara; Ceresini, Graziano; Verzicco, Ignazio; Ferrucci, Luigi; Ceda, Gian Paolo

    2014-01-01

    Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals.

  18. Determination of selected natural hormones and endocrine disrupting compounds in domestic wastewater treatment plants by liquid chromatography electrospray ionization tandem mass spectrometry after solid phase extraction.

    PubMed

    Muz, Melis; Sönmez, M Selcen; Komesli, Okan Tarık; Bakırdere, Sezgin; Gökçay, Celal Ferdi

    2012-02-21

    A new analytical method for the simultaneous determination of two natural hormones (progesterone and estrone) and two selected endocrine disrupter compounds (EDCs) (diltiazem and carbamazepine (Cbz)) was developed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) after pre-concentration with solid phase extraction (SPE). Influent and effluent samples taken from five different wastewater treatment plants throughout Turkey namely Hurma/Antalya, Lara/Antalya, Kemer-1 and Kemer-2 and METU/Ankara were analyzed for their EDCs contents under the optimum conditions. All of the parameters in the pre-concentration step were optimized and the best recoveries for all compounds of interest were achieved at pH 7 (about 100%). Progesterone was not detected in any of the treatment plants while diltiazem was found in all samples with the exception of Lara effluent.

  19. Anabolic steroids abuse and male infertility.

    PubMed

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage.

  20. Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development.

    PubMed

    Goodman, Julie E; Kerper, Laura E; Boyce, Catherine Petito; Prueitt, Robyn L; Rhomberg, Lorenz R

    2010-10-01

    Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case-control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Anabolic and androgenic activities of Bulbine natalensis stem in male Wistar rats.

    PubMed

    Yakubu, Musa T; Afolayan, Anthony J

    2010-05-01

    Aqueous extract of Bulbine natalensis Baker (Asphodelaceae) stem at 25, 50 and 100 mg/kg body weight was investigated for anabolic and androgenic effects in male Wistar rats. Sixty male rats were grouped into four (A-D) consisting of 15 each. Group A (control) was orally treated with 0.5 mL of distilled water for 14 days while groups B, C and D were treated like the control except they received 0.5 mL containing 25, 50, and 100 mg/kg body weight of the extract respectively. All the doses of the extract increased (P <0.05) the testicular-body weight ratio as well as alkaline phosphatase activity, glycogen, sialic acid, protein, and cholesterol content of the testes except the single administration of 100 mg/kg body weight which compared well (P>0.05) with the controls for glycogen and cholesterol. The testicular and serum testosterone concentration were increased except in the 100 mg/kg body weight where the effect on the tissue and serum hormone did not manifest until after the first and seven daily doses respectively. Testicular acid phosphatase activity, serum follicle stimulating and luteinizing hormone concentrations also increased at all the doses except in the 100 mg/kg body weight where the effect on the enzyme and the hormone did not manifest until after seven days. The increases were most pronounced in the 50 mg/kg body weight extract treated animals. The results indicate anabolic and androgenic activities of Bulbine natalensis stem in male rat testes with the 50 mg/kg body weight of the extract exhibiting the highest anabolizing and androgenic activities. These activities further support the folkloric use of the plant most especially at 50 mg/kg body weight in the management of male sexual dysfunction in South Africa.

  2. Compound

    NASA Astrophysics Data System (ADS)

    Suzumura, Akitoshi; Watanabe, Masaki; Nagasako, Naoyuki; Asahi, Ryoji

    2014-06-01

    Recently, Cu-based chalcogenides such as Cu3SbSe4, Cu2Se, and Cu2SnSe3 have attracted much attention because of their high thermoelectric performance and their common feature of very low thermal conductivity. However, for practical use, materials without toxic elements such as selenium are preferable. In this paper, we report Se-free Cu3SbS4 thermoelectric material and improvement of its figure of merit ( ZT) by chemical substitutions. Substitutions of 3 at.% Ag for Cu and 2 at.% Ge for Sb lead to significant reductions in the thermal conductivity by 37% and 22%, respectively. These substitutions do not sacrifice the power factor, thus resulting in enhancement of the ZT value. The sensitivity of the thermal conductivity to chemical substitutions in these compounds is discussed in terms of the calculated phonon dispersion and previously proposed models for Cu-based chalcogenides. To improve the power factor, we optimize the hole carrier concentration by substitution of Ge for Sb, achieving a power factor of 16 μW/cm K2 at 573 K, which is better than the best reported for Se-based Cu3SbSe4 compounds.

  3. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    EPA Science Inventory

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  4. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    EPA Science Inventory

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  5. PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling.

    PubMed

    Esen, Emel; Lee, Seung-Yon; Wice, Burton M; Long, Fanxin

    2015-11-01

    Teriparatide, a recombinant peptide corresponding to amino acids 1-34 of human parathyroid hormone (PTH), has been an effective bone anabolic drug for over a decade. However, the mechanism whereby PTH stimulates bone formation remains incompletely understood. Here we report that in cultures of osteoblast-lineage cells, PTH stimulates glucose consumption and lactate production in the presence of oxygen, a hallmark of aerobic glycolysis, also known as Warburg effect. Experiments with radioactively labeled glucose demonstrate that PTH suppresses glucose entry into the tricarboxylic acid cycle (TCA cycle). Mechanistically, the increase in aerobic glycolysis is secondary to insulin-like growth factor (Igf) signaling induced by PTH, whereas the metabolic effect of Igf is dependent on activation of mammalian target of rapamycin complex 2 (mTORC2). Importantly, pharmacological perturbation of glycolysis suppresses the bone anabolic effect of intermittent PTH in the mouse. Thus, stimulation of aerobic glycolysis via Igf signaling contributes to bone anabolism in response to PTH. © 2015 American Society for Bone and Mineral Research.

  6. Anabolic and Catabolic Biomarkers As Predictors of Muscle Strength Decline: The InCHIANTI Study

    PubMed Central

    Maggio, Marcello; Lauretani, Fulvio; Bandinelli, Stefania; Ceda, Gian Paolo; Di Iorio, Angelo; Giallauria, Francesco; Guralnik, Jack M.; Ferrucci, Luigi

    2010-01-01

    Abstract Background Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength. Methods In a representative sample of 716 men and women aged ≥65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-α receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up. Results In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones. Conclusions Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging. PMID:20230273

  7. Effect of rejuvenation hormones on spermatogenesis.

    PubMed

    Moss, Jared L; Crosnoe, Lindsey E; Kim, Edward D

    2013-06-01

    To review the current literature for the effect of hormones used in rejuvenation clinics on the maintenance of spermatogenesis. Review of published literature. Not applicable. Men who have undergone exogenous testosterone (T) and/or anabolic androgenic steroid (AAS) therapies. None. Semen analysis, pregnancy outcomes, and time to recovery of spermatogenesis. Exogenous testosterone and anabolic androgenic steroids suppress intratesticular testosterone production, which may lead to azoospermia or severe oligozoospermia. Therapies that protect spermatogenesis involve human chorionic gonadotropin (hCG) therapy and selective estrogen receptor modulators (SERMs). The studies examining the effect of human growth hormone (HGH) on infertile men are uncontrolled and unconvincing, but they do not appear to negatively impact spermatogenesis. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. The use of hormones for rejuvenation is increasing with the aging of the Baby Boomer population. Men desiring children at a later age may be unaware of the side-effect profile of hormones used at rejuvenation centers. Testosterone and anabolic androgenic steroids have well-established detrimental effects on spermatogenesis, but recovery may be possible with cessation. Clomiphene citrate, human growth hormone (HGH)/insulin-like growth factor-1 (IGF-1), human chorionic gonadotropin (hCG), and aromatase inhibitors do not appear to have significant negative effects on sperm production, but quality data are lacking. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. [Rhabdomyolysis in a bodybuilder using anabolic steroids].

    PubMed

    Hageloch, W; Appell, H J; Weicker, H

    1988-09-01

    The clinical course and the laboratory findings of a massive rhabdomyolysis in a male bodybuilder is presented. Particularly spectacular are the light- and electron-microscopical pictures of the histological findings. The acute renal failure as the most important and major life-threatening complication of the rhabdomyolysis is considered and the successful therapeutic procedure is described. The probability of a causal relation between anabolic steroids and rhabdomyolysis is discussed as well as the resulting consequences for the care of athletes in sports medicine.

  9. [Effect of anabolic steroid on immune response].

    PubMed

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

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

  10. Effects of Perfluoroalkyl Compounds on mRNA Expression Levels of Thyroid Hormone-Responsive Genes in Primary Cultures of Avian Neuronal Cells

    PubMed Central

    Vongphachan, Viengtha; Cassone, Cristina G.; Wu, Dongmei; Chiu, Suzanne; Crump, Doug; Kennedy, Sean W.

    2011-01-01

    There is growing interest in assessing the neurotoxic and endocrine disrupting potential of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, prenatal and postnatal development and behavior. PFC exposure altered hormone levels and the expression of hormone-responsive genes in mammalian and aquatic species. This study is the first to assess the effects of PFCs on messenger RNA (mRNA) expression in primary cultures of neuronal cells in two avian species: the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following thyroid hormone (TH)–responsive genes were examined using real-time reverse transcription-PCR: type II iodothyronine 5′-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif–binding factor (Oct-1), and myelin basic protein. Several PFCs altered the mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. Short-chained PFCs (less than eight carbons) altered the expression of TH-responsive genes (D2, D3, TTR, and RC3) in chicken embryonic neuronal cells to a greater extent than long-chained PFCs (more than or equal to eight carbons). Variable transcriptional changes were observed in herring gull embryonic neuronal cells exposed to short-chained PFCs; mRNA levels of Oct-1 and RC3 were upregulated. This is the first study to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and may provide insight into the possible mechanisms of action of PFCs in the avian brain. PMID:21212296

  11. Acute myocardial infarction in a young man using anabolic steroids.

    PubMed

    Wysoczanski, Mariusz; Rachko, Maurice; Bergmann, Steven R

    2008-01-01

    Anabolic-androgenic steroids are used worldwide to help athletes gain muscle mass and strength. Their use and abuse is associated with numerous side effects, including acute myocardial infarction (MI). We report a case of MI in a young 31-year-old bodybuilder. Because of the serious cardiovascular complications of anabolic steroids, physicians should be aware of their abuse and consequences.

  12. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.

    PubMed

    Stephenson, Kenna; Neuenschwander, Pierre F; Kurdowska, Anna K

    2013-01-01

    Menopause impacts 25 million women world wide each year, and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030. Menopause has been associated with symptoms of hot flashes, night sweats, dysphoric mood, sleep disturbance, and conditions of cardiovascular disease, depression, osteoporosis, osteoarthritis, depression, dementia, and frailty. Conventional hormone replacement therapy results in increased thrombotic events, and an increased risk of breast cancer and dementia as evidenced in large prospective clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women's Health Initiative. A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors. Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile, yet long-term studies of this treatment model are lacking. The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol, estradiol, progesterone, DHEA, and testosterone on cardiovascular biomarkers, hemostatic, inflammatory, immune signaling factors; quality-of-life measures; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care. A prospective, cohort, closed-label study received approval from the Human Subjects Committee. Recruitment from outpatient clinics at an academic medical center and the community at large resulted in three hundred women giving signed consent. Seventy-five women who met strict inclusion/exclusion criteria were enrolled. Baseline hormone evaluation was performed along with baseline experimental measures. Following this, women received compounded transdermal bioidentical hormone therapy of BiEst (80%Estriol/20%Estradiol), and

  13. Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels.

    PubMed

    Eguchi, Akifumi; Nomiyama, Kei; Minh Tue, Nguyen; Trang, Pham Thi Kim; Hung Viet, Pham; Takahashi, Shin; Tanabe, Shinsuke

    2015-02-01

    This study demonstrated the contamination levels of polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), hydroxylated PBDEs (OH-PBDEs), and bromophenols (BPhs), and their relationships with thyroid hormones (THs), in the serum of human donors from an e-waste recycling site and a rural site in Hung Yen province, Vietnam. Occupationally related exposure was indicated by significantly higher residue levels of PCBs, OH-PCBs, PBDEs, and BPhs in the serum of donors from the e-waste recycling site (median: 420, 160, 290, and 300pgg(-1) wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200pgg(-)(1) wet wt, respectively). On the other hand, levels of OH-/MeO-PBDEs were significantly higher in serum of donors from the reference site (median: 160 and 20pgg(-1) wet wt, respectively) than in those from the e-waste recycling site (median: 43 and 0.52pgg(-1) wet wt, respectively). In addition, we implemented stepwise generalized linear models to assess the association between the levels of TH and PCBs, PBDEs, and their related compounds. In females, we found positive associations of PCBs and OH-PCB concentrations with total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine, and a negative association with thyroid-stimulating hormone concentrations.

  14. Determination of steroid sex hormones and related synthetic compounds considered as endocrine disrupters in water by liquid chromatography-diode array detection-mass spectrometry.

    PubMed

    López de Alda, M J; Barceló, D

    2000-09-15

    In this study, a procedure for the determination of various naturally occurring hormones and of some related synthetic chemicals, commonly used for birth control and treatment of certain hormonal disorders and cancers, in water is described. The procedure includes solid-phase extraction of 0.5 l of water and subsequent analysis of the extract by liquid chromatography with diode array detection and mass spectrometric detection in series (LC-DAD-MS). DAD has been performed at 197, 225, and 242 nm for quantification and confirmatory identification purposes. For MS detection two interfaces--electrospray and atmospheric pressure chemical ionization--in both the positive and the negative ion mode have been tested and the MS parameters influencing the MS signal optimized. DAD and MS have been intercompared for selectivity, sensitivity, precision, and linearity of response. Selected conditions have been applied to the determination of six estrogens (17beta-estradiol, estriol, estrone, ethynylestradiol, mestranol, and diethylstilbestrol) and four progestogens (progesterone, levonorgestrel, norethindrone and ethynodiol diacetate) in several types of water bodies, including sewage influents and effluents, surface water and drinking water. Recoveries greater than 83% and detection limits in the ng/l range have been achieved for most compounds.

  15. Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

    SciTech Connect

    Gracia, Tannia Hilscherova, Klara; Jones, Paul D.; Newsted, John L.; Higley, Eric B.; Zhang, Xiaowei; Hecker, Markus; Murphy, Margaret B.; Yu, Richard M.K.; Lam, Paul K.S.; Wu, Rudolf S.S.; Giesy, John P.

    2007-12-01

    The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3{beta}HSD2, CYP11{beta}1, CYP11{beta}2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11{beta}2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11{beta}2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The {beta}-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.

  16. Changes in plasma adrenocorticotropic hormone and cortisol levels induced by intracerebroventricular injection of histamine and its related compounds in dogs.

    PubMed

    Tsujimoto, S; Kamei, C; Yoshida, T; Tasaka, K

    1993-08-01

    Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.

  17. The gonadotropin releasing hormone (GnRH)-like molecule in prosobranch Patella caerulea: potential biomarker of endocrine-disrupting compounds in marine environments.

    PubMed

    De Lisa, Emilia; Carella, Francesca; De Vico, Gionata; Di Cosmo, Anna

    2013-02-01

    It has been reported that endocrine disrupter compounds (EDCs) interfere with the endocrine system, mimicking the action of sex steroid hormones in different species of mollusks. Prosobranchs are frequently used as a reliable bioindicator to evaluate EDC exposure. In this article, we evaluate the effects of the xenoestrogen 4-n-nonylphenol (NP) in the prosobranch gastropod Patella caerulea, which exhibits protandrous hermaphroditism as its reproductive strategy. We isolated a partial sequence of a GnRH-like molecule from the gonads of Patella caerulea. The deduced amino acid sequence is highly homologous to that reported for the Lottia gigantea GnRH. Patella caerulea GnRH (pGnRH) mRNA expression is widespread in both male and female germ lines during gametogenesis. We suggest pGnRH as a novel biomarker for the early assessment of presence of EDCs and monitoring short and long-term impacts on Patella caerulea community structure.

  18. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

    PubMed

    Thevis, Mario; Schänzer, Wilhelm

    2010-01-01

    The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

  19. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  20. Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

    PubMed Central

    Reschly, E.J.; Krasowski, M.D.

    2008-01-01

    The NR1I subfamily of nuclear hormone receptors includes the 1,25-(OH)2-vitamin D3 receptor (VDR; NR1I1), pregnane X receptor (PXR; NR1I2), and constitutive androstane receptor (CAR; NR1I3). PXR and VDR are found in diverse vertebrates from fish to mammals while CAR is restricted to mammals. Current evidence suggests that the CAR gene arose from a duplication of an ancestral PXR gene, and that PXR and VDR arose from duplication of an ancestral gene, represented now by a single gene in the invertebrate Ciona intestinalis. Aside from the high-affinity effects of 1,25-(OH)2-vitamin D3 on VDRs, the NR1I subfamily members are functionally united by the ability to bind potentially toxic endogenous compounds with low affinity and initiate changes in gene expression that lead to enhanced metabolism and elimination (e.g., induction of cytochrome P450 3A4 expression in humans). The detoxification role of VDR seems limited to sensing high concentrations of certain toxic bile salts, such as lithocholic acid, whereas PXR and CAR have the ability to recognize structurally diverse compounds. PXR and CAR show the highest degree of cross-species variation in the ligand-binding domain of the entire vertebrate nuclear hormone receptor superfamily, suggesting adaptation to species-specific ligands. This review examines the insights that phylogenetic and experimental studies provide into the function of VDR, PXR, and CAR, and how the functions of these receptors have expanded to evolutionary advantage in humans and other animals. PMID:16724925

  1. Chemometric and chemoinformatic analyses of anabolic and androgenic activities of testosterone and dihydrotestosterone analogues.

    PubMed

    Alvarez-Ginarte, Yoanna María; Crespo-Otero, Rachel; Marrero-Ponce, Yovani; Noheda-Marin, Pedro; Garcia de la Vega, Jose Manuel; Montero-Cabrera, Luis Alberto; Ruiz García, José Alberto; Caldera-Luzardo, José A; Alvarado, Ysaias J

    2008-06-15

    activities and high values of eta produce unfavorable effects. The found MDs can also be efficiently used in similarity studies based on cluster analysis. Our model for the anabolic/androgenic ratio (expressed by weight of levator ani muscle, LA, and seminal vesicle, SV, in mice) predicts that the 2-aminomethylene-17alpha-methyl-17beta-hydroxy-5alpha-androstan-3-one (43) compound is the most potent anabolic steroid, and the 17alpha-methyl-2beta,17beta-dihydroxy-5alpha-androstane (31) compound is the least potent one of this series. The approach described in this report is an alternative for the discovery and optimization of leading anabolic compounds among steroids and analogues. It also gives an important role to electron exchange terms of molecular interactions to this kind of steroid activity.

  2. Anabolic steroids for treating pressure ulcers.

    PubMed

    Naing, Cho; Whittaker, Maxine A

    2017-06-20

    Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The ulcers usually arise over a bony prominence, and are recognised as a common medical problem affecting people confined to a bed or wheelchair for long periods of time. Anabolic steroids are used as off-label drugs (drugs which are used without regulatory approval) and have been used as adjuvants to usual treatment with dressings, debridement, nutritional supplements, systemic antibiotics and antiseptics, which are considered to be supportive in healing of pressure ulcers. Anabolic steroids are considered because of their ability to stimulate protein synthesis and build muscle mass. Comprehensive evidence is required to facilitate decision making, regarding the benefits and harms of using anabolic steroids. To assess the effects of anabolic steroids for treating pressure ulcers. In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Published or unpublished randomised controlled trials (RCTs) comparing the effects of anabolic steroids with alternative treatments or different types of anabolic steroids in the treatment of pressure ulcers. Two review authors independently carried out study selection, data extraction and risk of bias assessment. The review contains only one trial with a total of 212 participants, all with spinal cord injury and open pressure ulcers classed as stage III and IV. The participants were

  3. Mechanical signals as anabolic agents in bone.

    PubMed

    Ozcivici, Engin; Luu, Yen Kim; Adler, Ben; Qin, Yi-Xian; Rubin, Janet; Judex, Stefan; Rubin, Clinton T

    2010-01-01

    Aging and a sedentary lifestyle conspire to reduce bone quantity and quality, decrease muscle mass and strength, and undermine postural stability, culminating in an elevated risk of skeletal fracture. Concurrently, a marked reduction in the available bone-marrow-derived population of mesenchymal stem cells (MSCs) jeopardizes the regenerative potential that is critical to recovery from musculoskeletal injury and disease. A potential way to combat the deterioration involves harnessing the sensitivity of bone to mechanical signals, which is crucial in defining, maintaining and recovering bone mass. To effectively utilize mechanical signals in the clinic as a non-drug-based intervention for osteoporosis, it is essential to identify the components of the mechanical challenge that are critical to the anabolic process. Large, intense challenges to the skeleton are generally presumed to be the most osteogenic, but brief exposure to mechanical signals of high frequency and extremely low intensity, several orders of magnitude below those that arise during strenuous activity, have been shown to provide a significant anabolic stimulus to bone. Along with positively influencing osteoblast and osteocyte activity, these low-magnitude mechanical signals bias MSC differentiation towards osteoblastogenesis and away from adipogenesis. Mechanical targeting of the bone marrow stem-cell pool might, therefore, represent a novel, drug-free means of slowing the age-related decline of the musculoskeletal system.

  4. Mechanical signals as anabolic agents in bone

    PubMed Central

    Ozcivici, Engin; Luu, Yen Kim; Adler, Ben; Qin, Yi-Xian; Rubin, Janet; Judex, Stefan; Rubin, Clinton T.

    2013-01-01

    Aging and a sedentary lifestyle conspire to reduce bone quantity and quality, decrease muscle mass and strength, and undermine postural stability, culminating in an elevated risk of skeletal fracture. Concurrently, a marked reduction in the available bone-marrow-derived population of mesenchymal stem cells (MSCs) jeopardizes the regenerative potential that is critical to recovery from musculoskeletal injury and disease. A potential way to combat the deterioration involves harnessing the sensitivity of bone to mechanical signals, which is crucial in defining, maintaining and recovering bone mass. To effectively utilize mechanical signals in the clinic as a non-drug-based intervention for osteoporosis, it is essential to identify the components of the mechanical challenge that are critical to the anabolic process. Large, intense challenges to the skeleton are generally presumed to be the most osteogenic, but brief exposure to mechanical signals of high frequency and extremely low intensity, several orders of magnitude below those that arise during strenuous activity, have been shown to provide a significant anabolic stimulus to bone. Along with positively influencing osteoblast and osteocyte activity, these low-magnitude mechanical signals bias MSC differentiation towards osteoblastogenesis and away from adipogenesis. Mechanical targeting of the bone marrow stem-cell pool might, therefore, represent a novel, drug-free means of slowing the age-related decline of the musculoskeletal system. PMID:20046206

  5. Update on maximal anabolic response to dietary protein.

    PubMed

    Kim, Il-Young; Deutz, Nicolaas E P; Wolfe, Robert R

    2017-06-01

    The anabolic response to dietary protein can be defined as the difference between protein synthesis and breakdown, or the net protein balance, in response to ingestion of protein alone or a mixed meal containing protein. Others have concluded that a maximal anabolic response can be achieved with ingestion of 20-35 g of a high quality protein, leading to the formulation of a popular concept that the maximal anabolic response can be achieved by distributing the total protein intake evenly throughout the day, rather than eating a majority of dietary protein with dinner. However, this concept was based entirely on the measurement of muscle protein synthesis and thus ignored the potential contributions of suppression of protein breakdown to the anabolic response, as well as the possibility that tissues and organs other than muscle may also play a role in the anabolic response. In this review we discuss the factors comprising the total anabolic response, discuss relevant methodological issues, derive a theoretical maximal anabolic response based on current literature values, and interpret recent papers addressing the issue of maximal anabolic response as well as meal distribution of dietary protein. We conclude that it is not likely that there is a practical limit to the maximal anabolic response to a single meal, and the most efficient way in which to maximize the total anabolic response over a 24-h period is to increase dietary protein at breakfast and lunch without reducing protein intake with dinner. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  6. Behaviour and hormonal status in healthy rats on a diet rich in Maillard reaction products with or without solvent extractable aroma compounds.

    PubMed

    Sebeková, Katarína; Klenovics, Kristína Simon; Boor, Peter; Celec, Peter; Behuliak, Michal; Schieberle, Peter; Heidland, August; Palkovits, Miklós; Somoza, Veronika

    2012-02-01

    Maillard reaction products (MRPs) are generated upon thermal processing of foods, modifying their colour and flavour. We asked whether aroma compounds generated via Maillard-type reactions modulate the in vivo effects of MRP-rich diets (MRPD). Male Wistar rats were fed for 3weeks either with a standard rat chow, an aroma compounds containing MRPD comprising 25% bread crust, or an aroma-extracted MRPD. In contrast to standard rat chow, consumption of MRPDs affected glucose control, induced hyper-leptinemia and hyper-adiponectinemia. Plasma adipokines were significantly higher in rats on aroma containing MRPD in comparison with those consuming aroma-extracted MRPD. Consumption of both MRPDs significantly increased the expression of the insulin receptor in the olfactory bulb, and mildly in the hypothalamus. Administration of the aroma containing MRPD significantly increased the leptin receptor expression in the olfactory bulb, and in the hypothalamus. Under both MRPDs, strong expression of c-fos indicated an increased neuronal activity in the olfactory bulb. Neuronal activity in brain areas involved in the central regulation of food intake and energy homeostasis was more pronounced in rats fed by the aroma containing MRPD. In conclusion, short-term consumption of a MRPD fortified with bread crust, particularly if containing solvent extractable volatile aroma compounds, affected the leptin-induced central signalling of anorexigenic/orexigenic hormones, and the neuronal activity in the central nervous system. Behavioural changes and altered glucose control were more evident in rats on the aroma containing MRPD. Our data suggest that volatile aroma compounds in foods might affect endocrine signalling and neuronal regulation of metabolism. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting.

    PubMed

    Gullett, Norleena P; Hebbar, Gautam; Ziegler, Thomas R

    2010-04-01

    This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.

  8. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting1234

    PubMed Central

    Gullett, Norleena P; Hebbar, Gautam

    2010-01-01

    This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting. PMID:20164318

  9. Effect-directed analysis to explore the polar bear exposome: identification of thyroid hormone disrupting compounds in plasma.

    PubMed

    Simon, Eszter; van Velzen, Martin; Brandsma, Sicco H; Lie, Elisabeth; Løken, Katharina; de Boer, Jacob; Bytingsvik, Jenny; Jenssen, Bjørn M; Aars, Jon; Hamers, Timo; Lamoree, Marja H

    2013-08-06

    Compounds with transthyretin (TTR)-binding potency in the blood plasma of polar bear cubs were identified with effect-directed analysis (EDA). This approach contributes to the understanding of the thyroid disrupting exposome of polar bears. The selection of these samples for in-depth EDA was based on the difference between the observed TTR-binding potency on the one hand and the calculated potency (based on known concentrations of TTR-binding compounds and their relative potencies) on the other. A library-based identification was applied to the liquid chromatography-time-of-flight-mass spectrometry (LC-ToF-MS) data by screening for matches between compound lists and the LC-ToF-MS data regarding accurate mass and isotope pattern. Then, isotope cluster analysis (ICA) was applied to the LC-ToF-MS data allowing specific screening for halogen isotope patterns. The presence of linear and branched nonylphenol (NP) was observed for the first time in polar bears. Furthermore, the presence of one di- and two monohydroxylated octachlorinated biphenyls (octaCBs) was revealed in the extracts. Linear and branched NP, 4'-OH-CB201 and 4,4'-OH-CB202 could be successfully confirmed with respect to their retention time in the analytical system. In addition, branched NP, mono- and dihydroxylated-octaCBs showed TTR-binding potencies and could explain another 32 ± 2% of the total measured activities in the extracts.

  10. Restoration of anabolic deficit and muscle glycogen consumption in competitive orienteering.

    PubMed

    Johansson, C; Tsai, L; Hultman, E; Tegelman, R; Pousette, A

    1990-06-01

    Consumption and restoration of muscle glycogen and changes in anabolic and catabolic steroid hormones were analyzed in five male elite orienteers during and after an orienteering competition. The magnitude of glycogen consumption and pronounced increase in serum-cortisol during the orienteering race reflect the great muscular output demands during forest running. The free testosterone/cortisol ratio was normalized to the initial level within four hours post-exercise. Synchronously, only 25% of the muscle glycogen loss was restored. Within 24 hours post-exercise all runners showed normalized levels of testosterone, cortisol and free testosterone/cortisol ratio. The glycogen content was also restored except in one of the runners. We conclude that daily orienteering competitions per se do not seem to create risks for developing a state of hormonal imbalance or significant decrease in glycogen when the carbohydrate supply is appropriate.

  11. The current preference for the immuno-analytical ELISA method for quantitation of steroid hormones (endocrine disruptor compounds) in wastewater in South Africa.

    PubMed

    Manickum, Thavrin; John, Wilson

    2015-07-01

    requirements for steroid hormone quantitation. Further optimization of the sensitivity of the chemical-analytical LC-tandem mass spectrometry methods, especially for wastewater screening, in South Africa is required. Risk assessment studies showed that it was not practical to propose standards or allowable limits for the steroid estrogens E1, E2, EE2, and E3; the use of predicted-no-effect concentration values of the steroid estrogens appears to be appropriate for use in their risk assessment in relation to aquatic organisms. For raw water sources, drinking water, raw and treated wastewater, the use of bioassays, with trigger values, is a useful screening tool option to decide whether further examination of specific endocrine activity may be warranted, or whether concentrations of such activity are of low priority, with respect to health concerns in the human population. The achievement of improved quantitation limits for immuno-analytical methods, like ELISA, used for compound quantitation, and standardization of the method for measuring E2 equivalents (EEQs) used for biological activity (endocrine: e.g., estrogenic) are some areas for future EDC research.

  12. Integration of ligand and structure-based virtual screening for identification of leading anabolic steroids.

    PubMed

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; García-de la Vega, José Manuel; Bencomo-Martínez, Alberto; Pupo, Amaury; Agramonte-Delgado, Alina; Marrero-Ponce, Yovani; Ruiz-García, José Alberto; Mikosch, Hans

    2013-11-01

    Parallel ligand- and structure-based virtual screenings of 269 steroids with anabolic activity evaluated in vivo were performed. The quantitative structure-activity relationship (QSAR) model expressed by selected descriptors as the octanol-water partition coefficient, the molar volume and the quantum mechanical calculated charge values on atoms C1, C2, C5, C9, C10, C14 and C17 of the steroid skeleton, expresses structural features of anabolic steroids (AS) contributing to the transport and steroid-receptor interaction. On the other hand, computational simulations of a candidate ligand binding to a receptor study (a "docking" procedure) predict the association of these AS with the human androgen receptor (AR). Fourteen compounds were identified as lead; the most potent was the 7α-methylestr-4-en-3, 17-dione. It was concluded that a good anabolic activity requires hydrogen bonding interactions between both Arg752 and Gln711 residues in the cycles A with O3 atom of the steroid and either Asn705 and Thr877 residues in the cycles D of steroid with O17 atom. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Analysis of anabolic steroids in hair: time courses in guinea pigs.

    PubMed

    Shen, Min; Xiang, Ping; Yan, Hui; Shen, Baohua; Wang, Mengye

    2009-09-01

    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.

  14. Prevalence of Anabolic Steroid Use Among Illinois High School Students

    PubMed Central

    Tuttle, Leslye D.; Gaa, Gregory L.; Griffith, Edwin H.; Cahill, Bernard R.

    1994-01-01

    This study was conducted to quantify anabolic steroid use in Illinois, investigate student knowledge and perception of anabolic steroid use, and identify characteristics of the anabolic steroid user. We surveyed 3047 freshman and senior high school students from 38 high schools, randomly selected from three school enrollment sizes and five geographic locations, using a six-page anonymous questionnaire. Anabolic steroid use was reported by 58 (1.9%) of the participants, 44 of 1477 (3%) males and 14 of 1562 (0.9%) females. Thirty-four of 1679 (2%) freshman and 24 of 1366 (1.8%) seniors reported use. Anabolic steroids were used in all possible school enrollment sizes and geographic locations (matrix cells). Four (7%) of the users reported starting at age 10 or younger. A teacher/coach was reported as a primary source by 8 (14%) of the users, as well as identified by 11 (19%) of the users as the individual they knew using anabolic steroids. It appears that anabolic steroids are being introduced to students in elementary and junior high schools, and that teachers/coaches are actively involved in their use. PMID:16558283

  15. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  16. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  17. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  18. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  19. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  20. Anabolic actions of Notch on mature bone

    PubMed Central

    Liu, Peng; Ping, Yilin; Ma, Meng; Zhang, Demao; Liu, Connie; Zaidi, Samir; Gao, Song; Ji, Yaoting; Lou, Feng; Yu, Fanyuan; Lu, Ping; Stachnik, Agnes; Bai, Mingru; Wei, Chengguo; Zhang, Liaoran; Wang, Ke; Chen, Rong; New, Maria I.; Rowe, David W.; Yuen, Tony; Sun, Li; Zaidi, Mone

    2016-01-01

    Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response. PMID:27036007

  1. Anabolic androgenic steroid-induced hepatotoxicity.

    PubMed

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. [Control measures for anabolic androgenic steroid medicines].

    PubMed

    Vázquez-Mourelle, Raquel; Carracedo-Martínez, Eduardo; Ces Gens, Eugenio; Cadórniga Valiño, Luis; Álvaro Esteban, Pilar; Pose Reino, José Manuel

    2015-01-01

    Anabolic androgenic steroids (AAS) can cause serious adverse effects when used without a therapeutic purpose. This article aims to show that the AAS are susceptible to being sold on the black market. We also aim to describe how certain limitations on the health inspection services of the Galician health service to pursue these illegal actions prompted a regulatory initiative demanding that additional actions be granted to community pharmacies when dispensing AAS. Four pharmacy inspections detected the diversion of a total of 3118 packages of AAS, which led to the opening of four disciplinary proceedings. In two of these, specialized police forces were called in as there was sufficient evidence of possible diversion to gymnasiums, resulting in a police operation called Operation Fitness.

  3. Anabolic androgenic steroids abuse and liver toxicity.

    PubMed

    Neri, M; Bello, S; Bonsignore, A; Cantatore, S; Riezzo, I; Turillazzi, E; Fineschi, V

    2011-05-01

    In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.

  4. Hepatocellular carcinoma associated with recreational anabolic steroid use.

    PubMed

    Gorayski, P; Thompson, C H; Subhash, H S; Thomas, A C

    2008-01-01

    A 35-year-old male bodybuilder was found to have a hepatocellular carcinoma (HCC) arising in a pre-existing hepatic adenoma following recreational anabolic steroid use. Given the widespread use of recreational anabolic steroids, another potentially life-threatening complication is highlighted in addition to the more commonly recognised hepatic adenoma. Malignant transformation to HCC from a pre-existing hepatic adenoma confirmed by immunohistochemical study has previously not been reported in athletes taking anabolic steroids. Further studies using screening programmes to identify high-risk individuals are recommended.

  5. [Research progresses of anabolic steroids analysis in doping control].

    PubMed

    Long, Yuanyuan; Wang, Dingzhong; Li, Ke'an; Liu, Feng

    2008-07-01

    Anabolic steroids, a kind of physiological active substance, are widely abused to improve athletic performance in human sports. They have been forbidden in sports by the International Olympic Committee since 1983. Since then, many researchers have been focusing their attentions on the establishment of reliable detection methods. In this paper, we review the research progresses of different analytical methods for anabolic steroids since 2002, such as gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, immunoassay, electrochemistry analysis and mass spectrometry. The developing prospect of anabolic steroids analysis is also discussed.

  6. Adverse health effects of anabolic-androgenic steroids.

    PubMed

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm.

  7. Impact of anabolic androgenic steroids on adolescent males.

    PubMed

    Lumia, Augustus R; McGinnis, Marilyn Y

    2010-06-01

    Anabolic androgenic steroid (AAS) use increased dramatically among adolescent males. This review focuses on studies using animal models of AAS exposure during adolescence which is a hormonally sensitive developmental period. AAS exposure during this critical period has wide-ranging consequences, including increased dendritic spine density, altered brain serotonin levels and escalated aggression in response to physical provocation. Human data suggest that AAS induces indiscriminate and unprovoked aggression often described as "'roid rage". However, animal studies indicate that the behavioral impact of AAS is modulated by experiential and social contingencies, a perceived provocation, and the chemical composition of the AAS. The AAS, testosterone increases aggression in juvenile and adult male rats when physically provoked. In contrast, stanzolol, inhibits aggression in both juvenile and adult male rats, even when physically provoked. Nandrolone has minimal effects on aggression, unless preceded by attack training. Exposure to AAS during adolescence may have a host of unintended bio-behavioral consequences. Yet, the perception of harmlessness surrounds AAS use. The perception of harmlessness is promoted by the availability of AAS especially through internet pharmacies. The perception of acceptability is reflected in current cultural ethics that no longer condemn cheating to obtain personal achievement or success. A prevailing conviction is that although AAS are illegal they are not really bad. Reduction of the availability of AAS to adolescents requires ardent legislative and legal intervention. The problem of acceptability can be addressed by educating adolescents about the short-term and long-term effects of AAS on brain and behavior, to increase awareness of the potential consequences of AAS use that apply directly to them.

  8. Screening for anabolic steroids in urine of forensic cases using fully automated solid phase extraction and LC-MS-MS.

    PubMed

    Andersen, David W; Linnet, Kristian

    2014-01-01

    A screening method for 18 frequently measured exogenous anabolic steroids and the testosterone/epitestosterone (T/E) ratio in forensic cases has been developed and validated. The method involves a fully automated sample preparation including enzyme treatment, addition of internal standards and solid phase extraction followed by analysis by liquid chromatography-tandem mass spectrometry (LC-MS-MS) using electrospray ionization with adduct formation for two compounds. Urine samples from 580 forensic cases were analyzed to determine the T/E ratio and occurrence of exogenous anabolic steroids. Extraction recoveries ranged from 77 to 95%, matrix effects from 48 to 78%, overall process efficiencies from 40 to 54% and the lower limit of identification ranged from 2 to 40 ng/mL. In the 580 urine samples analyzed from routine forensic cases, 17 (2.9%) were found positive for one or more anabolic steroids. Only seven different steroids including testosterone were found in the material, suggesting that only a small number of common steroids are likely to occur in a forensic context. The steroids were often in high concentrations (>100 ng/mL), and a combination of steroids and/or other drugs of abuse were seen in the majority of cases. The method presented serves as a fast and automated screening procedure, proving the suitability of LC-MS-MS for analyzing anabolic steroids. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. High throughput identification and quantification of anabolic steroid esters by atmospheric solids analysis probe mass spectrometry for efficient screening of drug preparations.

    PubMed

    Doué, Mickael; Dervilly-Pinel, Gaud; Gicquiau, Audrey; Pouponneau, Karinne; Monteau, Fabrice; Le Bizec, Bruno

    2014-06-17

    Recent developments in ambient mass spectrometry (AMS), such as atmospheric solids analysis probe (ASAP) mass spectrometry, open a whole new range of possibilities to screen for drug preparations. In this study, the potential of ASAP for the rapid identification and quantification of anabolic steroid esters has been evaluated. These compounds are known to be used both in human and in food producing animals to enhance performances and to improve the rate of growth, respectively. Using a triple quadrupole (QqQ) MS instrument, mechanism of ionization and fragmentation in both positive and negative mode were studied for a range of 21 selected steroid esters (based on testosterone, estradiol, nandrolone, and boldenone) which highlighted common neutral mass loss of 96.1, thus allowing rapid screening in minutes to reveal steroid ester presence with minimal sample preparation. Ester identification is further achieved through an efficient 2 min workflow on a QqQ MS instrument. Moreover, the use of isotope labeled internal standards permitted the quantification of the corresponding steroid esters in selected reaction monitoring (SRM) mode, for the first time in ASAP. This approach was successfully applied for characterization of oily commercial preparations. These results open new perspectives in hormone (and drug) rapid analysis by ASAP-MS in the near future.

  10. Multiple arterial thromboses associated with anabolic androgenic steroids.

    PubMed

    McCulloch, Neil Arthur; Abbas, Jonathan Raihan; Simms, Malcolm Harold

    2014-03-01

    The use of supraphysiological doses of anabolic androgenic steroids can have serious side effects. This article reports the case of a young man who suffered potentially life-threatening arterial thromboses following the use of these drugs.

  11. Analysis of anabolic steroids in the horse: development of a generic ELISA for the screening of 17alpha-alkyl anabolic steroid metabolites.

    PubMed

    Hungerford, Natasha L; Sortais, Benoît; Smart, Corrine G; McKinney, Andrew R; Ridley, Damon D; Stenhouse, Allen M; Suann, Craig J; Munn, Kellie J; Sillence, Martin N; McLeod, Malcolm D

    2005-08-01

    Due to the potential for misuse of a wide range of anabolic steroids in horse racing, a screening test to detect multiple compounds, via a common class of metabolites, would be a valuable forensic tool. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect 17alpha-alkyl anabolic steroid metabolites in equine urine. 16beta-Hydroxymestanolone (16beta,17beta-dihydroxy-17alpha-methyl-5alpha-androstan-3-one) was synthesised in six steps from commercially available epiandrosterone (3beta-hydroxy-5alpha-androstan-17-one). Polyclonal antibodies were raised in sheep, employing mestanolone (17beta-hydroxy-17alpha-methyl-5alpha-androstan-3-one) or 16beta-hydroxymestanolone conjugated to human serum albumin, via a 3-carboxymethyloxime linker, as antigens. Antibody cross-reactivities were determined by assessing the ability of a library of 54 representative steroids to competitively bind the antibodies. Antibodies raised against 16beta-hydroxymestanolone showed excellent cross-reactivities for all of the 16beta,17beta-dihydroxy-17alpha-methyl steroids analysed and an ELISA has been developed to detect these steroid metabolites. Using this 16beta-hydroxymestanolone assay, urine samples from horses administered with stanozolol (17alpha-methyl-pyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol), were analysed raw, following beta-glucuronidase hydrolysis, and following solid-phase extraction (SPE) procedures. The suppressed absorbances observed were consistent with detection of the metabolite 16beta-hydroxystanozolol. Positive screening results were confirmed by comparison with standard LCMS analyses. Antibodies raised against mestanolone were also used to develop an ELISA and this was used to detect metabolites retaining the parent D-ring structure following methandriol (17alpha-methylandrost-5-ene-3beta,17beta-diol) administration. The ELISA methods developed have application as primary screening tools for detection of new and known anabolic steroid metabolites.

  12. Multidetection Of Anabolic Androgenic Steroids Using Immunoarrays and Pattern Recognition Techniques

    NASA Astrophysics Data System (ADS)

    Calvo, D.; Salvador, J. P.; Tort, N.; Centi, F.; Marco, M. P.; Marco, S.

    2009-05-01

    A first step towards the multidetection of anabolic androgenic steroids by Enzyme-linked immunosorbent assays (ELISA) has been performed in this study. This proposal combines an array of classical ELISA assays with different selectivities and multivariate data analysis techniques. Data has been analyzed by principal component analysis in conjunction with a k-nearest line classifier has been used. This proposal allows to detect simultaneously four different compounds in the range of concentration from 10-1.5 to 103 mM with a total rate of 90.6% of correct detection.

  13. Medical issues associated with anabolic steroid use: are they exaggerated?

    PubMed

    Hoffman, Jay R; Ratamess, Nicholas A

    2006-01-01

    For the past 50 years anabolic steroids have been at the forefront of the controversy surrounding performance enhancing drugs. For almost half of this time no attempt was made by sports governing bodies to control its use, and only recently have all of the major sports governing bodies in North America agreed to ban from competition and punish athletes who test positive for anabolic steroids. These punitive measures were developed with the primary concern for promotion of fair play and eliminating potential health risks associated with androgenic-anabolic steroids. Yet, controversy exists whether these testing programs deter anabolic steroid use. Although the scope of this paper does not focus on the effectiveness of testing, or the issue of fair play, it is of interest to understand why many athletes underestimate the health risks associated from these drugs. What creates further curiosity is the seemingly well-publicized health hazards that the medical community has depicted concerning anabolic steroidabuse. Is there something that the athletes know, or are they simply naïve regarding the dangers? The focus of this review is to provide a brief history of anabolic steroid use in North America, the prevalence of its use in both athletic and recreational populations and its efficacy. Primary discussion will focus on health issues associated with anabolic steroid use with an examination of the contrasting views held between the medical community and the athletes that are using these ergogenic drugs. Existing data suggest that in certain circumstances the medical risk associated with anabolic steroid use may have been somewhat exaggerated, possibly to dissuade use in athletes. Key PointsFor many years the scientific and medical communities depicted a lack of efficacy and serious adverse effects from anabolic steroid use.Clinical case studies continue to link anabolic steroid administration with myocardial infarct, suicide, and cancer, evidence to support a cause and

  14. Medical Issues Associated with Anabolic Steroid Use: Are They Exaggerated?

    PubMed Central

    Hoffman, Jay R.; Ratamess, Nicholas A.

    2006-01-01

    For the past 50 years anabolic steroids have been at the forefront of the controversy surrounding performance enhancing drugs. For almost half of this time no attempt was made by sports governing bodies to control its use, and only recently have all of the major sports governing bodies in North America agreed to ban from competition and punish athletes who test positive for anabolic steroids. These punitive measures were developed with the primary concern for promotion of fair play and eliminating potential health risks associated with androgenic-anabolic steroids. Yet, controversy exists whether these testing programs deter anabolic steroid use. Although the scope of this paper does not focus on the effectiveness of testing, or the issue of fair play, it is of interest to understand why many athletes underestimate the health risks associated from these drugs. What creates further curiosity is the seemingly well-publicized health hazards that the medical community has depicted concerning anabolic steroidabuse. Is there something that the athletes know, or are they simply naïve regarding the dangers? The focus of this review is to provide a brief history of anabolic steroid use in North America, the prevalence of its use in both athletic and recreational populations and its efficacy. Primary discussion will focus on health issues associated with anabolic steroid use with an examination of the contrasting views held between the medical community and the athletes that are using these ergogenic drugs. Existing data suggest that in certain circumstances the medical risk associated with anabolic steroid use may have been somewhat exaggerated, possibly to dissuade use in athletes. Key Points For many years the scientific and medical communities depicted a lack of efficacy and serious adverse effects from anabolic steroid use. Clinical case studies continue to link anabolic steroid administration with myocardial infarct, suicide, and cancer, evidence to support a cause

  15. Detection of anabolic steroid abuse using a yeast transactivation system.

    PubMed

    Zierau, Oliver; Lehmann, Sylvi; Vollmer, Günter; Schänzer, Willhelm; Diel, Patrick

    2008-10-01

    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

  16. Dying to be big: a review of anabolic steroid use.

    PubMed Central

    Perry, H M; Wright, D; Littlepage, B N

    1992-01-01

    Anabolic steroids use is commonly perceived to be the domain of the higher echelons of competitive athletes. However, a great deal of anabolic steroid use occurs in private gymnasia (non-local authority) among non-competitive recreational athletes. Our study has attempted to give an insight into the prevalence of the use of these drugs, the hazards associated with it, and the public health responses which we have adopted. PMID:1490220

  17. Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

    PubMed Central

    Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

    2015-01-01

    Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p < 0.001). In the overall group of 24 treated plus untreated former users, 7 (29%) had experienced major depressive episodes during AAS withdrawal; 4 of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

  18. ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.

    PubMed

    Gopalaswamy, Vinaya; Dhibar, Deba Prasad; Gupta, Vipin; Arya, Ashutosh Kumar; Khandelwal, Niranjan; Bhansali, Anil; Garg, Sudhir Kumar; Agarwal, Neelam; Rao, Sudhaker D; Bhadada, Sanjay Kumar

    2017-06-01

    Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 μg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 μg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. Weekly teriparatide therapy (60 μg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.

  19. [Anabolic steroids: damages, effect on performance, and on metabolism (author's transl)].

    PubMed

    Keul, J; Deus, B; Kindermann, W

    1976-03-19

    10 normal persons (age: x=22 years) and 15 weight lifters (age: x=27 years) were studied before and three months after taking Nandrolone danoate (ND). Strength exercises, hear rate during ergometer work, physical working capacity and certain biochemical variables were measured in the experimental group, as well as in a controll group of 7 weight lifters. Six weight lifters in the experimental group who had been taking ND for at least 3 years were also studied to determine whether there were any deleterious effects on their health. In addition, 75 athletes who had been taking anabolic steroids were investigated to determine the possible effects. It was found that: 1. In spite of an 7% increase in performance, the maximal heart rate was not higher when the subjects took ND. During submaximal work loads the heart rate (p less than 0.025) and the blood lactate level (p less than 0.05) were lower. During physical work, there was essentially no effect of ND on glucose or total lipids in serum. 2. The results from the three-months study, from the weight lifters taking ND for 3 years, as well as from 26 of the 57 athletes who had been taking ND showed no evidence of a deleterious effect of ND (based on 26 biochemical measurements). It would appear, therefore, that the general suggestion of a detrimental effect of anabolic hormones is not justified. 3. Damages or functional disturbances were found in 31 athletes and 3 weight lifters of the experimental group after oral application of anabolic alkyl-steroids. After a period of time without alkyl-steroid administration, all investigated biochemical parameters returned to normal levels; thus it appears that the aforementioned pathological findings are reversible changes in liver function.

  20. Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise.

    PubMed

    Kraemer, William J; Ratamess, Nicholas A; Nindl, Bradley C

    2017-03-01

    The complexity and redundancy of the endocrine pathways during recovery related to anabolic function in the body belie an oversimplistic approach to its study. The purpose of this review is to examine the role of resistance exercise (RE) on the recovery responses of three major anabolic hormones, testosterone, growth hormone(s), and insulin-like growth factor 1. Each hormone has a complexity related to differential pathways of action as well as interactions with binding proteins and receptor interactions. Testosterone is the primary anabolic hormone, and its concentration changes during the recovery period depending on the upregulation or downregulation of the androgen receptor. Multiple tissues beyond skeletal muscle are targeted under hormonal control and play critical roles in metabolism and physiological function. Growth hormone (GH) demonstrates differential increases in recovery with RE based on the type of GH being assayed and workout being used. IGF-1 shows variable increases in recovery with RE and is intimately linked to a host of binding proteins that are essential to its integrative actions and mediating targeting effects. The RE stress is related to recruitment of muscle tissue with the glandular release of hormones as signals to target tissues to support homeostatic mechanisms for metabolism and tissue repair during the recovery process. Anabolic hormones play a crucial role in the body's response to metabolism, repair, and adaptive capabilities especially in response to anabolic-type RE. Changes of these hormones following RE during recovery in the circulatory biocompartment of blood are reflective of the many mechanisms of action that are in play in the repair and recovery process. Copyright © 2017 the American Physiological Society.

  1. Protein Anabolic Resistance in Cancer: Does it really exist?

    PubMed Central

    Engelen, Mariëlle P. K. J.; van der Meij, Barbara S.; Deutz, Nicolaas E. P.

    2016-01-01

    Purpose of review Preventing unintentional weight and muscle loss is of crucial importance to maintain the condition and well-being of patients with cancer, improve treatment response and tolerance, and prolong survival. Anabolic resistance might explain why some cancer patients do not respond to nutritional intervention but does recent evidence actually support this? We will discuss recent literature that cast doubt on attenuated anabolic potential in cancer. Recent findings Although anabolic resistance was observed in the past, more recent studies have shown that advanced cancer patients have an anabolic potential after intake of high-quality proteins. Furthermore a consistent linear relationship is observed in cancer between (essential) amino acid availability from the diet and net protein gain. The studied cancer patients however were often characterized by a normal or obese body weight, following the trend in the general population, and mild systemic inflammation. Factors like recent chemotherapy, surgery or cachexia do not seem to attenuate the anabolic potential to feeding. Summary Cancer patients have a normal anabolic potential which relates to the amount of essential amino acids in the meal. It remains to be determined if this is also the case in weak cancer patients with a short life expectancy and high systemic inflammation. PMID:26560520

  2. Protein anabolic resistance in cancer: does it really exist?

    PubMed

    Engelen, Mariëlle P K J; van der Meij, Barbara S; Deutz, Nicolaas E P

    2016-01-01

    Preventing unintentional weight and muscle loss is of crucial importance to maintain the condition and well-being of patients with cancer, improve treatment response and tolerance, and prolong survival. Anabolic resistance might explain why some cancer patients do not respond to nutritional intervention, but does recent evidence actually support this? We will discuss recent literature that casts doubt on attenuated anabolic potential in cancer. Although anabolic resistance was observed in the past, more recent studies have shown that advanced cancer patients have an anabolic potential after intake of high-quality proteins. Furthermore, a consistent linear relationship is observed in cancer between (essential) amino acid availability from the diet and net protein gain. The studied cancer patients, however, were often characterized by a normal or obese body weight, following the trend in the general population, and mild systemic inflammation. Factors like recent chemotherapy, surgery, or cachexia do not seem to attenuate the anabolic potential to feeding. Cancer patients have a normal anabolic potential which relates to the amount of essential amino acids in the meal. It remains to be determined if this is also the case in weak cancer patients with a short life expectancy and high systemic inflammation.

  3. Multimodal nutrition/anabolic therapy for wasting conditions.

    PubMed

    Balstad, Trude Rakel; Kaasa, Stein; Solheim, Tora Skeidsvoll

    2014-05-01

    Significant progress has been made in the field of defining and describing the pathophysiology of wasting conditions such as cachexia. The number of new promising drugs, nutritional therapy alternatives, and exercise/rehabilitation programs is increasing. The purpose of this review is to give an overview of recent clinical findings from intervention studies investigating multimodal anabolic therapies utilizing drug, nutritional, and/or exercise interventions in order to counteract wasting. Anabolic agents such as ghrelin and selective androgen receptor modulators are under late-phase clinical testing and hold promise as new therapies, and their ability to mitigate weight loss and improve muscle mass and physical function is evaluated. In the past 2 years, eight new studies investigating interventions with anabolic potential in wasting have been published, among which three of these studies were multimodal. Targeted anabolic therapies aiming to prevent or reverse wasting might involve a combination of anabolic pharmacologic drugs, nutrition, and physical exercise working concurrently to enhance muscle protein synthesis and reduce breakdown. Some anabolic pharmacological interventions demonstrate the potential to improve muscle mass, but the multimodal interventions seem in greater extent to also demonstrate improvement in physical function.

  4. Phytosterols and anabolic agents versus designer drugs.

    PubMed

    De Brabander, H F; Verheyden, K; Mortier, V; Le Bizec, B; Verbeke, W; Courtheyn, D; Noppe, H

    2007-03-14

    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13C/12C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.

  5. Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone.

    PubMed

    Etoh, Masaya; Yamaguchi, Akira

    2010-11-01

    Various animal experiments and human studies have shown that intermittent injections of parathyroid hormone (PTH) exert anabolic effects on bone, whereas continuous PTH treatment decreases the bone mass and causes hypercalcemia in animals. However, limited data are available with regard to the effects of a repetitive regimen of continuous treatments of PTH followed by periodic withdrawals on the bone metabolism. We investigated the effects of this regimen by comparing the findings of intermittent and continuous PTH treatments in rats. Infusions of PTH for 24 h followed by 6-day withdrawal periods from PTH transiently increased the serum calcium levels on day 1, but these levels were within the normocalcemic range. The repetition of 4 cycles of continuous PTH infusions followed by PTH withdrawals as well as intermittent PTH treatment increased the trabecular bone thickness, osteoblast surface, and bone formation rate. Continuous PTH infusions followed by PTH withdrawals also increased the cortical thickness of the femoral diaphysis and the osteoid volume in trabecular bones, whereas the continuous treatment failed to induce these changes. These findings suggest that continuous PTH treatment followed by PTH withdrawal is a potential regimen that can induce the anabolic effects of PTH in bone metabolism without inducing hypercalcemia.

  6. Anabolic steroids, acute myocardial infarction and polycythemia: a case report and review of the literature.

    PubMed

    Stergiopoulos, Kathleen; Brennan, Joseph J; Mathews, Robin; Setaro, John F; Kort, Smadar

    2008-01-01

    The association between testosterone-replacement therapy and cardiovascular risk remains unclear with most reports suggesting a neutral or possibly beneficial effect of the hormone in men and women. However, several cardiovascular complications including hypertension, cardiomyopathy, stroke, pulmonary embolism, fatal and nonfatal arrhythmias, and myocardial infarction have been reported with supraphysiologic doses of anabolic steroids. We report a case of an acute ST-segment elevation myocardial infarction in a patient with traditional cardiac risk factors using supraphysiologic doses of supplemental, intramuscular testosterone. In addition, this patient also had polycythemia, likely secondary to high-dose testosterone. The patient underwent successful percutaneous intervention of the right coronary artery. Phlebotomy was used to treat the polycythemia acutely. We suggest that the chronic and recent "stacked" use of intramuscular testosterone as well as the resultant polycythemia and likely increased plasma viscosity may have been contributing factors to this cardiovascular event, in addition to traditional coronary risk factors. Physicians and patients should be aware of the clinical consequences of anabolic steroid abuse.

  7. Exposure to anabolic-androgenic steroids shortens life span of male mice.

    PubMed

    Bronson, F H; Matherne, C M

    1997-05-01

    Adult male laboratory mice were exposed for 6 months to a combination of four anabolic-androgenic steroids of the kinds and at the relative levels to which human athletes and body builders expose themselves. The four steroids included testosterone, two 17-alkylated steroids, and an ester, and they were given at doses that totaled either 5 or 20 times normal androgenic maintenance levels for mice. By the time the survivors were 20 months old (1 yr after the termination of steroid exposure), 52% of the mice given the high dose of steroids had died compared with 35% of the mice given the low dose and only 12% of the control mice given no exogenous hormones (P < 0.001). Autopsy of the steroid-treated mice typically revealed tumors in the liver or kidney, other kinds of damage to these two organs, broadly invase lymphosarcomas, or heart damage, and usually more than one of these conditions. It can be concluded that the life span of male mice is decreased dramatically by exposing them for 6 months to the kinds and relative levels of anabolic steroids used by many athletes and body builders.

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

    PubMed

    Celec, Peter; Jáni, Peter; Smreková, Lucia; Mrlian, Andrej; Kúdela, Matús; Hodosy, Július; Boor, Peter; Kristová, Viera; Jakubovský, Ján; Jezová, Daniela; Halcák, Lukác; Bozek, Peter; Slámová, Judita; Ulicná, Ol'ga; Hojsík, Dalibor; Jurkovicová, Ingrid

    2003-12-12

    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.

  9. Determination of anabolic agents in dietary supplements by liquid chromatography-high-resolution mass spectrometry.

    PubMed

    Odoardi, Sara; Castrignanò, Erika; Martello, Simona; Chiarotti, Marcello; Strano-Rossi, Sabina

    2015-01-01

    A sensitive method for the identification and quantification of anabolic steroids and clenbuterol at trace levels in dietary supplements by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) in atmospheric pressure ionisation (APCI) mode using a single-stage Orbitrap analyser operating at a resolution power of 100 000 full width at half maximum (FWHM) was developed and validated. A total of 1 g of dietary supplement was added with testosterone-d3 as internal standard, dissolved in methanol, evaporated to dryness, diluted in sodium hydroxide solution and extracted with a mixture of pentane/ethyl ether 9:1. The extract was directly injected into the LC-HRMS system. The method was fully validated. Limits of detection (LODs) obtained for anabolic androgenic steroids (AASs) varied from 1 to 25 ng g(-1) and the limit of quantitation (LOQ) was 50 ng g(-1) for all analytes. The calibration was linear for all compounds in the range from the LOQ to 2000 ng g(-1), with correlation coefficients always higher than 0.99. Accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Good values of matrix effect and recovery were achieved. The ease of the sample preparation together with a fast run time of only 16 min permitted rapid identification of the analytes. The method was applied to the analysis of 30 dietary supplements in order to check for the presence of anabolic agents not labelled as being present in these supplements. Many AASs were often detected in the same sample: indeed, androstenedione was detected in nine supplements, 5-androsten-3β-ol-17-one (DHEA) in 12, methandienone in three, stanozolol in one, testosterone in seven and testosterone esters in four of them. A retrospective analysis of suspected compounds not included at the beginning of the method development was also possible by means of the full acquisition spectra obtained with the HRMS technique.

  10. Determination of steroid hormones and related compounds in filtered and unfiltered water by solid-phase extraction, derivatization, and gas chromatography with tandem mass spectrometry

    USGS Publications Warehouse

    Foreman, William T.; Gray, James L.; ReVello, Rhiannon C.; Lindley, Chris E.; Losche, Scott A.; Barber, Larry B.

    2012-01-01

    A new analytical method has been developed and implemented at the U.S. Geological Survey National Water Quality Laboratory that determines a suite of 20 steroid hormones and related compounds in filtered water (using laboratory schedule 2434) and in unfiltered water (using laboratory schedule 4434). This report documents the procedures and initial performance data for the method and provides guidance on application of the method and considerations of data quality in relation to data interpretation. The analytical method determines 6 natural and 3 synthetic estrogen compounds, 6 natural androgens, 1 natural and 1 synthetic progestin compound, and 2 sterols: cholesterol and 3--coprostanol. These two sterols have limited biological activity but typically are abundant in wastewater effluents and serve as useful tracers. Bisphenol A, an industrial chemical used primarily to produce polycarbonate plastic and epoxy resins and that has been shown to have estrogenic activity, also is determined by the method. A technique referred to as isotope-dilution quantification is used to improve quantitative accuracy by accounting for sample-specific procedural losses in the determined analyte concentration. Briefly, deuterium- or carbon-13-labeled isotope-dilution standards (IDSs), all of which are direct or chemically similar isotopic analogs of the method analytes, are added to all environmental and quality-control and quality-assurance samples before extraction. Method analytes and IDS compounds are isolated from filtered or unfiltered water by solid-phase extraction onto an octadecylsilyl disk, overlain with a graded glass-fiber filter to facilitate extraction of unfiltered sample matrices. The disks are eluted with methanol, and the extract is evaporated to dryness, reconstituted in solvent, passed through a Florisil solid-phase extraction column to remove polar organic interferences, and again evaporated to dryness in a reaction vial. The method compounds are reacted with

  11. Cardiac autonomic dysfunction in anabolic steroid users.

    PubMed

    Maior, A S; Carvalho, A R; Marques-Neto, S R; Menezes, P; Soares, P P; Nascimento, J H M

    2013-10-01

    This study aimed to evaluate if androgenic-anabolic steroids (AAS) abuse may induce cardiac autonomic dysfunction in recreational trained subjects. Twenty-two men were volunteered for the study. The AAS group (n = 11) utilized AAS at mean dosage of 410 ± 78.6 mg/week. All of them were submitted to submaximal exercise testing using an Astrand-Rhyming protocol. Electrocardiogram (ECG) and respired gas analysis were monitored at rest, during, and post-effort. Mean values of VO2 , VCO2 , and VE were higher in AAS group only at rest. The heart rate variability variables were calculated from ECG using MATLAB-based algorithms. At rest, AAS group showed lower values of the standard deviation of R-R intervals, the proportion of adjacent R-R intervals differing by more than 50 ms (pNN50), the root mean square of successive differences (RMSSD), and the total, the low-frequency (LF) and the high-frequency (HF) spectral power, as compared to Control group. After submaximal exercise testing, pNN50, RMSSD, and HF were lower, and the LF/HF ratio was higher in AAS group when compared to control group. Thus, the use of supraphysiological doses of AAS seems to induce dysfunction in tonic cardiac autonomic regulation in recreational trained subjects.

  12. Standardization of hormone determinations.

    PubMed

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. A ten-year assessment of anabolic steroid misuse among competitive athletes in Puerto Rico.

    PubMed

    Acevedo, P; Jorge, J C; Cruz-Sánchez, A; Amy, E; Barreto-Estrada, J L

    2011-10-01

    Little is known about anabolic androgenic steroids (AAS) misuse in the Caribbean region in spite of increased popularity among athletes and adolescents. The present study examines the usage of AAS among competitive athletes in Puerto Rico. Doping test results of competitive athletes obtained by random sampling out of competition during the 2000-2009 period were analysed. Doping tests were executed by the Centre for Sports, Health and Exercise Sciences (Albergue Olímpico, Salinas, Puerto Rico). A total of 550 athletes were monitored during 2000-2009. Information was collected with regard to competitive sport, gender and AAS compounds whenever a positive test result was encountered. From the total sample of monitored cases during the past decade, 5.4% showed adverse analytical findings. Anabolic androgenic steroids misuse was detected among male (62%) and female (38%) athletes. Weightlifting showed the greatest percentage of positive AAS doping test results (70% of total cases) and stanozolol was the most commonly misused exogenous androgen (60% of abused AAS whether alone or as part of a cocktail). Testosterone was the most common endogenous misused steroid (10% of misused compounds). In Puerto Rico, AAS misuse was detected across competitive sports for both genders. Although AAS misuse among Puerto Rican athletes shares some features that are consistent with the international sports community, it is imperative to address AAS misuse in the Caribbean region.

  14. A Ten-year Assessment of Anabolic Steroid Misuse among Competitive Athletes in Puerto Rico

    PubMed Central

    Acevedo, P; Jorge, JC; Cruz-Sánchez, A; Amy, E; Barreto-Estrada, JL

    2012-01-01

    Objective Little is known about anabolic androgenic steroids (AAS) misuse in the Caribbean region in spite of increased popularity among athletes and adolescents. The present study examines the usage of AAS among competitive athletes in Puerto Rico. Methods Doping test results of competitive athletes obtained by random sampling out of competition during the 2000–2009 period were analysed. Doping tests were executed by the Centre for Sports, Health and Exercise Sciences (Albergue Olímpico, Salinas, Puerto Rico). A total of 550 athletes were monitored during 2000–2009. Information was collected with regard to competitive sport, gender and AAS compounds whenever a positive test result was encountered. Results From the total sample of monitored cases during the past decade, 5.4% showed adverse analytical findings. Anabolic androgenic steroids misuse was detected among male (62%) and female (38%) athletes. Weightlifting showed the greatest percentage of positive AAS doping test results (70% of total cases) and stanozolol was the most commonly misused exogenous androgen (60% of abused AAS whether alone or as part of a cocktail). Testosterone was the most common endogenous misused steroid (10% of misused compounds). Conclusion In Puerto Rico, AAS misuse was detected across competitive sports for both genders. Although AAS misuse among Puerto Rican athletes shares some features that are consistent with the international sports community, it is imperative to address AAS misuse in the Caribbean region. PMID:22519228

  15. Androgenic anabolic steroids and arterial structure and function in male bodybuilders.

    PubMed

    Sader, M A; Griffiths, K A; McCredie, R J; Handelsman, D J; Celermajer, D S

    2001-01-01

    The study examined arterial and cardiac structure and function in bodybuilders using androgenic anabolic steroids (AAS), compared to non-steroid-using bodybuilder controls. Adverse cardiovascular events have been reported in bodybuilders taking anabolic steroids. The cardiovascular effects of AAS, however, have not been investigated in detail. We recruited 20 male bodybuilders (aged 35 +/- 3 years), 10 actively using AAS and 10 who denied ever using steroids. Serum lipid and hormone levels, carotid intima-media thickness (IMT), arterial reactivity, and left ventricular (LV) dimensions were measured. Vessel diameter was measured by ultrasound at rest, during reactive hyperemia (an endothelium-dependent response, leading to flow-mediated dilation, FMD), and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). Arterial reactivity was also measured in 10 age-matched non-bodybuilding sedentary controls. Use of AAS was associated with significant decreases in high density lipoprotein cholesterol, sex hormone binding globulin, testosterone and gonadotrophin levels, and significant increases in LV mass and self-reported physical strength (p < 0.05). Carotid IMT (0.60 +/- 0.04 mm vs. 0.63 +/- 0.07 mm), arterial FMD (4.7 +/- 1.4% vs. 4.1 +/- 0.7%) and GTN responses (11.0 +/- 1.9% vs. 14.4 +/- 1.7%) were similar in both bodybuilding groups (p > 0.2). The GTN responses were significantly lower and carotid IMT significantly higher in both bodybuilding groups, however, compared with the non-bodybuilding sedentary controls (p = 0.01). Although high-level bodybuilding is associated with impaired vascular reactivity and increased arterial thickening, the use of AAS per se is not associated with significant abnormalities of arterial structure or function.

  16. Androgenic anabolic steroid use among male adolescents in Falkenberg.

    PubMed

    Nilsson, S

    1995-01-01

    Recent reports show that androgenic anabolic steroids are used by many teenagers, not as a deliberate attempt to give them strength, better athletic performance, etc., but to improve their looks. The so-called macho cult among young boys tempts them into using androgenic anabolic steroids to give them bigger muscles and a more powerful appearance. This study was undertaken to investigate the prevalence of androgenic anabolic steroid use among teenagers in a small town and to create a platform for future work with the aim of decreasing the misuse of these drugs. In Falkenberg, a town in the county of Halland in the west of Sweden, the pupils at two high schools were investigated by means of an anonymous multiple-choice questionnaire. A total of 1383 students (688 males and 695 females) aged 14-19 years participated in the study, giving a participation rate of 96%. The number of answers completed was 99%. The use of androgenic anabolic steroids is a reality among male teenagers in Falkenberg, with 5.8% of them using the drugs. Among 15- to 16-year-old boys misuse of these drugs is as high as 10%, and of these 50% (5.0% of total) also inject ampoules of the drugs. This prevalence is alarming since the adverse effects of androgenic anabolic steroids are more serious in teenagers. Serious action must be taken to inform teenagers of the consequences of misusing drugs.

  17. Anabolic and androgenic activities of 19-nor-testosterone steroids: QSAR study using quantum and physicochemical molecular descriptors.

    PubMed

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; de la Vega, José Manuel García; Noheda-Marín, Pedro; Marrero-Ponce, Yovani; Ruíz-García, José Alberto

    2011-08-01

    Quantitative structure-activity relationship (QSAR) study of 19-nor-testosterone steroids family was performed using quantum and physicochemical molecular descriptors. The quantum-chemical descriptors were calculated using semiempirical calculations. The descriptor values were statistically correlated using multi-linear regression analysis. The QSAR study indicated that the electronic properties of these derivatives have significant relationship with observed biological activities. The found QSAR equations explain that the energy difference between the LUMO and HOMO, the total dipole moment, the chemical potential and the value of the net charge of different carbon atoms in the steroid nucleus showed key interaction of these steroids with their anabolic-androgenic receptor binding site. The calculated values predict that the 17α-cyclopropyl-17β, 3β-hydroxy-4-estrene compound presents the highest anabolic-androgenic ratio (AAR) and the 7α-methyl-17β-acetoxy-estr-4-en-3-one compound the lowest AAR. This study might be helpful in the future successful identification of "real" or "virtual" anabolic-androgenic steroids.

  18. Training increases anabolic response and reduces inflammatory response to a single practice in elite male adolescent volleyball players.

    PubMed

    Nemet, Dan; Portal, Shawn; Zadik, Zvi; Pilz-Burstein, Rutie; Adler-Portal, Dana; Meckel, Yoav; Eliakim, Alon

    2012-01-01

    We examined the effect of training on hormonal and inflammatory response to a single volleyball practice in elite adolescent players. Fourteen male, elite, national team-level, Israeli volleyball players (age, 16.3±1.1 years, Tanner stage 4-5) participated in the study. Blood samples were collected before and immediately after a typical 60-min volleyball practice, before and after 7 weeks of training during the initial phases of the volleyball season. Hormonal measurements included the anabolic hormones growth hormone (GH), insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, and testosterone; the catabolic hormone cortisol; the pro-inflammatory markers interleukin (IL) 6, and the anti-inflammatory marker IL-1 receptor antagonist. Training led to a significant improvement of both anaerobic and aerobic properties. Before the training intervention, the typical volleyball practice was associated with a significant increase of GH and testosterone and also with a significant increase of IL-6. Training resulted in a significantly greater GH response (ΔGH, 2.5±2.4 vs. 4.7±3.0 ng/mL, before and after training, respectively; p<0.02) and reduced IL-6 response (ΔIL-6, 2.0±1.6 vs. 0.6±0.7 pg/mL, before and after training, respectively; p<0.01) to the same relative intensity volleyball practice. The results suggest that, along with the improvement of anaerobic and aerobic characteristics, training leads to a greater anabolic and reduced inflammatory response to exercise.

  19. Current status and bioanalytical challenges in the detection of unknown anabolic androgenic steroids in doping control analysis.

    PubMed

    Pozo, Oscar J; De Brabanter, Nik; Fabregat, Andreu; Segura, Jordi; Ventura, Rosa; Van Eenoo, Peter; Deventer, Koen

    2013-11-01

    Androgenic anabolic steroids (AAS) are prohibited in sports due to their anabolic effects. Doping control laboratories usually face the screening of AAS misuse by target methods based on MS detection. Although these methods allow for the sensitive and specific detection of targeted compounds and metabolites, the rest remain undetectable. This fact opens a door for cheaters, since different AAS can be synthesized in order to evade doping control tests. This situation was evidenced in 2003 with the discovery of the designer steroid tetrahydrogestrinone. One decade after this discovery, the detection of unknown AAS still remains one of the main analytical challenges in the doping control field. In this manuscript, the current situation in the detection of unknown AAS is reviewed. Although important steps have been made in order to minimize this analytical problem and different analytical strategies have been proposed, there are still some drawbacks related to each approach.

  20. Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice.

    PubMed

    Yao, Gang-Qing; Wu, Jian-Jun; Troiano, Nancy; Insogna, Karl

    2011-03-01

    Parathyroid hormone (PTH) is a potent anabolic agent, but the cellular mechanisms by which it increases bone mass are not fully understood. Dickkopf 1 (Dkk1) is an endogenous inhibitor of Wnt signaling and suppresses bone formation in vivo. We sought to determine if Dkk1 and anabolic PTH treatment interact in regulating bone mass. PTH treatment of primary murine osteoblasts for 24 h reduced Dkk1 expression by 90% as quantified by real-time PCR, whereas PTH treatment in vivo reduced Dkk1 expression by 30% when given as a single daily subcutaneous dose. To directly determine whether Dkk1 modulates the anabolic response of PTH in vivo, we engineered transgenic (TG) mice expressing murine Dkk1 under the control of the 2.3-kb rat collagen alpha-1 promoter. TG mice had significantly reduced bone mass, which was accompanied by reduced histomorphometric parameters of bone formation (reduced OV/TV, ObS/OS, and NOb/TAR). Treatment of TG mice and wild-type (WT) littermates with 95 ng/g body weight of human (1-34) PTH daily for 34 days resulted in comparable increases in bone mass at all skeletal sites. Histomorphometric analyses indicated that PTH treatment increased the numbers of both osteoblasts and osteoclasts in WT mice but only increased the numbers of osteoblasts in TG mice. We conclude that overexpression of Dkk1 does not attenuate the anabolic response to PTH in vivo.

  1. Discovery of a Potent and Short−Acting Oral Calcilytic with a Pulsatile Secretion of Parathyroid Hormone

    PubMed Central

    2010-01-01

    Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have been considered as alternatives for parathyroid hormone (PTH), an injectable bone anabolic drug used in the treatment of osteoporosis. Previously, we identified aminopropandiol 1, which transiently stimulated endogenous PTH secretion in rats. However, the inhibition of cytochrome P450 (CYP) 2D6 and the low bioavailability of 1 remain to be solved. Attempts to change the physicochemical properties of the highly lipophilic amine 1 by introduction of a carboxylic acid group as well as further structural modifications led to the discovery of the highly potent biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a significantly improved bioavailability. Compound 15 evoked a rapid and transient elevation of endogenous PTH levels in rats after oral administration in a dose-dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern correlated with the pharmacokinetic profile and agreed well with that of the exogenous PTH injection which exerts a bone anabolic effect. PMID:24900301

  2. Discovery of a potent and short-acting oral calcilytic with a pulsatile secretion of parathyroid hormone.

    PubMed

    Shinagawa, Yuko; Inoue, Teruhiko; Katsushima, Takeo; Kiguchi, Toshihiro; Ikenogami, Taku; Ogawa, Naoki; Fukuda, Kenji; Hirata, Kazuyuki; Harada, Kazuhito; Takagi, Masaki; Nakagawa, Takashi; Kimura, Shuichi; Matsuo, Yushi; Maekawa, Mariko; Hayashi, Mikio; Soejima, Yuki; Takahashi, Mitsuru; Shindo, Masanori; Hashimoto, Hiromasa

    2011-03-10

    Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have been considered as alternatives for parathyroid hormone (PTH), an injectable bone anabolic drug used in the treatment of osteoporosis. Previously, we identified aminopropandiol 1, which transiently stimulated endogenous PTH secretion in rats. However, the inhibition of cytochrome P450 (CYP) 2D6 and the low bioavailability of 1 remain to be solved. Attempts to change the physicochemical properties of the highly lipophilic amine 1 by introduction of a carboxylic acid group as well as further structural modifications led to the discovery of the highly potent biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a significantly improved bioavailability. Compound 15 evoked a rapid and transient elevation of endogenous PTH levels in rats after oral administration in a dose-dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern correlated with the pharmacokinetic profile and agreed well with that of the exogenous PTH injection which exerts a bone anabolic effect.

  3. Anabolic steroids: what should the emergency physician know?

    PubMed

    Brown, James T

    2005-08-01

    Anabolic steroids have not currently made their way into the daily practice of emergency physicians. The patients that use and abuse them have. In addition, those patients that are suffering from the consequences of illnesses that have excess levels of androgens are commonly evaluated in the emergency department. Clinicians should familiarize themselves with the practices of anabolic steroid users, so they can provide more beneficial council to their patients. As research continues, the emergency physician may find uses for androgens within the emergency department.

  4. Manifestation of severe coronary heart disease after anabolic drug abuse.

    PubMed

    Mewis, C; Spyridopoulos, I; Kühlkamp, V; Seipel, L

    1996-02-01

    Anabolic steroids are frequently abused, thus increasing the risk of cardiovascular disease, despite the known unfavorable influence on lipid profiles. We report on a young bodybuilder who presented with ventricular tachycardia as the first manifestation of severe underlying coronary heart disease. Coronary angiogram revealed severe stenotic lesions in the right coronary artery and the left descending coronary artery, and hypokinetic regions corresponded to posterolateral and anterior myocardial infarctions. This young patient had a history without any coronary risk factors, but with a 2-year abuse of the anabolic steroid stanazolol. No report published so far has shown possible atherogenic consequences of long-term abuse of stanazolol.

  5. [Myocardial infarction and anabolic steroid use. A case report].

    PubMed

    Godon, P; Bonnefoy, E; Guérard, S; Munet, M; Velon, S; Brion, R; Touboul, P

    2000-07-01

    The potential cardiotoxicity of anabolic steroids is not well known. The authors report the case of a young man who was a top class body builder and who developed severe ischaemic cardiomyopathy presenting with an inferior wall myocardial infarction. The clinical history revealed prolonged and intensive usage of two types of anabolic steroids to be the only risk factor. This cardiotoxicity may be related to several physiopathological mechanisms: accelerated atherogenesis by lipid changes, increased platelet aggregation, coronary spasm or a direct toxic effect on the myocytes. The apparent scarcity of the reported clinical details in the literature is probably an underestimation of the consequences of this usage.

  6. Hepatic lesions in patients treated with synthetic anabolic steriods.

    PubMed Central

    Sweeney, E C; Evans, D J

    1976-01-01

    Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals. Images PMID:185239

  7. Hepatic lesions in patients treated with synthetic anabolic steriods.

    PubMed

    Sweeney, E C; Evans, D J

    1976-07-01

    Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals.

  8. On the Free Energy That Drove Primordial Anabolism

    PubMed Central

    Kaufmann, Michael

    2009-01-01

    A key problem in understanding the origin of life is to explain the mechanism(s) that led to the spontaneous assembly of molecular building blocks that ultimately resulted in the appearance of macromolecular structures as they are known in modern biochemistry today. An indispensable thermodynamic prerequisite for such a primordial anabolism is the mechanistic coupling to processes that supplied the free energy required. Here I review different sources of free energy and discuss the potential of each form having been involved in the very first anabolic reactions that were fundamental to increase molecular complexity and thus were essential for life. PMID:19468343

  9. Effects of Strength Training and Anabolic Steroid in the Peripheral Nerve and Skeletal Muscle Morphology of Aged Rats

    PubMed Central

    Krause Neto, Walter; Silva, Wellington de A.; Ciena, Adriano P.; Nucci, Ricardo Aparecido Baptista; Anaruma, Carlos A.; Gama, Eliane F.

    2017-01-01

    Thirty male 20-month-old Wistar rats were divided into groups: IC—initial control (n = 6), FC—final control (n = 6), AC—anabolic hormone control (n = 6), ST—strength trained (n = 6) and STA—strength trained with anabolic hormone (n = 6). All groups were submitted to adaptation, familiarization and maximum load carrying test (MLCT). Strength training (6–8×/session with loads of 50%–100% MLCT, 3×/week and pause of 120 s) was performed in ladder climbing (LC) for 15 weeks. The administration of testosterone propionate (TP) was performed 2×/week (10 mg/kg) in animals in the AC and STA groups. After the experimental period, animals were euthanized and the tibial nerve and plantaris muscle removed and prepared for electron transmission and histochemistry. To compare the groups we used one-way ANOVA (post hoc Bonferroni), student’s t-tests for pre vs. post (dependent and independent variables) comparisons and significance level set at p ≤ 0.05. The following significant results were found: (a) aging decreased the number of myelinated axon fibers; (b) use of isolated TP increased the diameter of myelinated fibers, along with increased thickness of myelin sheath; (c) ST increased area of myelinated and unmyelinated fibers, together with the myelin sheath. These changes made it possible to increase the area occupied by myelinated fibers keeping their quantity and also reduce the interstitial space; and (d) association of anabolic steroid and ST increased the area of unmyelinated axons and thickness of the myelin sheath. Compared to ST, both strategies have similar results. However, Schwann cells increased significantly only in this strategy. PMID:28713262

  10. Bioidentical Hormones for Menopausal Hormone Therapy: Variation on a Theme

    PubMed Central

    Bythrow, Jenna

    2007-01-01

    BACKGROUND Progesterone creams and natural or bioidentical compounded estrogen preparations are being promoted to consumers as safe alternatives to conventional menopausal hormone therapy and as health-promoting tonics. No reliable data support these claims. SAFETY Natural hormones, including estradiol, estriol, estrone, and progesterone, can be expected to have the same adverse event profile as conventional menopausal hormone regimens. SALIVARY HORMONE TESTS Salivary tests may be used to persuade asymptomatic consumers to use hormones (or symptomatic patients to use higher doses than those needed to mitigate symptoms), a practice that can be expected to result in adverse events. PMID:17549577

  11. Knowledge about Anabolic Steroids of Rhode Island Adolescents: Implications for Education Programs.

    ERIC Educational Resources Information Center

    Nutter, June

    Although anabolic steroids are associated with short term behavior and long term health problems, few schools address this issue. Adolescents were surveyed to determine their general knowledge of anabolic steroids, attitudes related to fair play, and interest in limiting anabolic steroid use. Data from 322 boys and 331 girls in grades 7-12 were…

  12. The Effect of Anabolic Steroid Education on Knowledge and Attitudes of At-Risk Preadolescents.

    ERIC Educational Resources Information Center

    Trenhaile, Jay; Choi, Hee-Sook; Proctor, Theron B.; Work, Patricia

    1998-01-01

    Investigates the effect of anabolic steroid education on preadolescents' knowledge of and attitudes toward anabolic steroids with 35 male athletes. Information on psychological and physiological aspects of anabolic steroid use, weight training techniques, nutrition, social decision making, and self-esteem training were provided. Participants…

  13. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

  14. Bleeding oesophageal varices associated with anabolic steroid use in an athlete.

    PubMed Central

    Winwood, P. J.; Robertson, D. A.; Wright, R.

    1990-01-01

    A 30 year old bodybuilder who had been taking anabolic steroids for 18 months presented with bleeding oesophageal varices. Serious liver disease secondary to anabolic steroids including peliosis hepatis, nodular hyperplasia and malignant change is well recognized. We report what is, to our knowledge, the first case of bleeding oesophageal varices associated with the use of anabolic steroids. PMID:2099434

  15. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  16. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  17. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  18. The Effect of Anabolic Steroid Education on Knowledge and Attitudes of At-Risk Preadolescents.

    ERIC Educational Resources Information Center

    Trenhaile, Jay; Choi, Hee-Sook; Proctor, Theron B.; Work, Patricia

    1998-01-01

    Investigates the effect of anabolic steroid education on preadolescents' knowledge of and attitudes toward anabolic steroids with 35 male athletes. Information on psychological and physiological aspects of anabolic steroid use, weight training techniques, nutrition, social decision making, and self-esteem training were provided. Participants…

  19. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  20. Confirmation and 3D profiling of anabolic steroid esters in injection sites using imaging desorption electrospray ionisation (DESI) mass spectrometry.

    PubMed

    de Rijke, Eva; Hooijerink, Dick; Sterk, Saskia S; Nielen, Michel W F

    2013-01-01

    In this study, desorption electrospray ionisation (DESI) linear ion trap tandem mass spectrometry (MS(n)) was applied for the confirmation and three-dimensional profiling of anabolic steroid esters in an injection site of bovine muscle. The spatial resolution of the DESI-MS(n) was demonstrated by scanning hormone esters and marker ink lines drawn at various distances on a microscopic slide at set distances, using an x-scanner with manual y and z adjustment. Tissue slices of bovine muscle injected with a hormone cocktail were analysed. All anabolic steroid esters could be directly detected in the sample and confirmed on the basis of identification points awarded for selected MS/MS transitions according to the performance criteria given in Commission Decision 2002/657/EC. Moreover, the injection site could be mapped by two-dimensional and three-dimensional imaging MS, showing a horizontal and vertical distribution through the muscle tissue. This DESI approach offers potential for analysis of injection sites of steroid esters from illegally treated animals; moreover, direct analysis by ambient imaging DESI-MS still allows conventional extraction and analysis of the whole tissue for further confirmatory or contra-analysis afterwards.

  1. Use of dried blood spots in doping control analysis of anabolic steroid esters.

    PubMed

    Tretzel, Laura; Thomas, Andreas; Geyer, Hans; Gmeiner, Günter; Forsdahl, Guro; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

    2014-08-05

    Dried blood spot (DBS) sampling, a technique for whole blood sampling on a piece of filter paper, has more than 50-years tradition, particularly in the diagnostic analysis of metabolic disorders in neonatal screening. Due to the minimal invasiveness, straightforwardness, robustness against manipulation and fastness DBS sampling recommends itself as an advantageous technique in doping control analysis. The present approach highlights the development of a screening assay for the analysis of eight anabolic steroid esters (nandrolone phenylpropionate, trenbolone enanthate, testosterone acetate, testosterone cypionate, testosterone isocaproate, testosterone phenylpropionate, testosterone decanoate and testosterone undecanoate) and nandrolone in DBS. The detection of the intact esters allows an unequivocal proof of the administration of conjugates of exogenous testosterone and its derivatives. Precise, specific and linear conditions were obtained by means of liquid chromatography high resolution/high accuracy mass spectrometry. Sensitivity in the low ppb range was accomplished by the preparation of the methyloxime derivatives of the target compounds. Labeled internal standards (d3-nandrolone, d3-nandrolone caproate and d3-nandrolone undecanoate) were applied to compensate for the broad range in chain length of the esters. The assay presented here outlines the application of DBS for the analysis of anabolic steroid esters in doping controls for the first time providing great potential to simplify the proof of exogenous administration of testosterone.

  2. Investigation of the composition of anabolic tablets using near infrared spectroscopy and Raman chemical imaging.

    PubMed

    Rebiere, Hervé; Ghyselinck, Céline; Lempereur, Laurent; Brenier, Charlotte

    2016-01-01

    The use of performance enhancing drugs is a widespread phenomenon in professional and leisure sports. A spectroscopic study was carried out on anabolic tablets labelled as 5 mg methandienone tablets provided by police departments. The analytical approach was based on a two-step methodology: a fast analysis of tablets using near infrared (NIR) spectroscopy to assess sample homogeneity based on their global composition, followed by Raman chemical imaging of one sample per NIR profile to obtain information on sample formulation. NIR spectroscopy assisted by a principal components analysis (PCA) enabled fast discrimination of different profiles based on the excipient formulation. Raman hyperspectral imaging and multivariate curve resolution - alternating least square (MCR-ALS) provided chemical images of the distribution of the active substance and excipients within tablets and facilitated identification of the active compounds. The combination of NIR spectroscopy and Raman chemical imaging highlighted dose-to-dose variations and succeeded in the discrimination of four different formulations out of eight similar samples of anabolic tablets. Some samples contained either methandienone or methyltestosterone whereas one sample did not contain an active substance. Other ingredients were sucrose, lactose, starch or talc. Both techniques were fast and non-destructive and therefore can be carried out as exploratory methods prior to destructive screening methods. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health.

    PubMed

    Abbate, V; Kicman, A T; Evans-Brown, M; McVeigh, J; Cowan, D A; Wilson, C; Coles, S J; Walker, C J

    2015-07-01

    Twenty-four products suspected of containing anabolic steroids and sold in fitness equipment shops in the United Kingdom (UK) were analyzed for their qualitative and semi-quantitative content using full scan gas chromatography-mass spectrometry (GC-MS), accurate mass liquid chromatography-mass spectrometry (LC-MS), high pressure liquid chromatography with diode array detection (HPLC-DAD), UV-Vis, and nuclear magnetic resonance (NMR) spectroscopy. In addition, X-ray crystallography enabled the identification of one of the compounds, where reference standard was not available. Of the 24 products tested, 23 contained steroids including known anabolic agents; 16 of these contained steroids that were different to those indicated on the packaging and one product contained no steroid at all. Overall, 13 different steroids were identified; 12 of these are controlled in the UK under the Misuse of Drugs Act 1971. Several of the products contained steroids that may be considered to have considerable pharmacological activity, based on their chemical structures and the amounts present. This could unwittingly expose users to a significant risk to their health, which is of particular concern for naïve users. Copyright © 2014 John Wiley & Sons, Ltd.

  4. In vivo and in vitro metabolism of the designer anabolic steroid furazadrol in thoroughbred racehorses.

    PubMed

    Waller, Christopher C; Cawley, Adam T; Suann, Craig J; Ma, Paul; McLeod, Malcolm D

    2016-05-30

    Furazadrol ([1',2']isoxazolo[4',5':2,3]-5α-androstan-17β-ol) is a designer anabolic androgenic steroid that is readily available via the internet. It contains an isoxazole fused to the steroid A-ring which offers metabolic stability and noteworthy anabolic activity raising concerns over the potential for abuse of this compound in equine sports. The metabolism of furazadrol was studied by in vivo and in vitro methods for the first time. Urinary furazadrol 17-sulfate and furazadrol 17-glucuronide metabolites were detected in vivo after a controlled administration and compared with synthetically-derived reference materials in order to confirm their identities. They were quantified to establish the excretion profile and a suitable limit of detection. Minor metabolites were also detected, including epifurazadrol, hydroxylated furazadrol, and hydroxylated and oxidised furazadrol, present as the sulfate and glucuronide conjugates. Phase II metabolites were subjected to enzymatic hydrolysis by Escherichia coli β-glucuronidase and Pseudomonas aeruginosa arylsulfatase to further confirm the identity of the corresponding phase I metabolites. The metabolism profile was compared to the products obtained from an in vitro phase I metabolism study, with all but two of the minor in vivo phase I metabolites observed in the in vitro system. These investigations identify the key urinary metabolites of furazadrol following oral administration, which can be incorporated into anti-doping screening and confirmation procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Determination of hormones, a plasticizer, preservatives, perfluoroalkylated compounds, and a flame retardant in water samples by ultrasound-assisted dispersive liquid-liquid microextraction based on the solidification of a floating organic drop.

    PubMed

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2015-10-01

    Dispersive liquid-liquid microextraction based on the solidification of a floating organic drop (DLLME-SFO) is a novel extraction technique commonly applied for the extraction on a specific group of compounds. In this paper, the applicability of ultrasound-assisted DLLME-SFO for multiresidue extraction has been evaluated. A method for the simultaneous extraction of four hormones (17α-ethinylestradiol, 17β-estradiol, estriol and estrone), a plasticizer (bisphenol A), three preservatives (methyl-, ethyl- and propylparaben), six perfluoroalkylated compounds (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, from C4 to C8), and a brominated flame retardant (hexabromocyclododecane) has been developed and validated for their extraction from surface water and tap water. Determination was carried out by high-performance liquid chromatography-tandem mass spectrometry in negative ionization mode. Recoveries of the target compounds were highly dependent on their log K(ow) values. Linear relationship between recoveries and log K(ow) values was observed for compounds from the same group (hormones, preservatives and perfluoroalkylated carboxylic acids). The lowest recoveries were obtained for the less hydrophobic compounds (estriol (43%), methylparaben (32%), ethylparaben (45%) and the perfluorinated compounds of shorter alkyl chain (C4: 17%, C5: 41% and C6: 57%)). Recoveries of the other pollutants were higher than 80%. Precision, expressed as relative standard deviation, was in the range from 1% to 16%. Method detection limits were in the range 0.001-1.126 µg L(-1), for surface water, and 0.001-1.446 µg L(-1) for tap water. No important matrix effect was observed. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

    Berning, Joseph M; Adams, Kent J; Stamford, Bryant A

    2004-11-01

    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.

  7. Chronic Ethanol Consumption Inhibits Postlactational Anabolic Rebuilding in Female Rats

    USDA-ARS?s Scientific Manuscript database

    Despite significant loss of bone during lactation, bone mineral density (BMD) is restored by a powerful anabolic rebuilding process following weaning. A significant number of women resume alcohol consumption after weaning their offspring from breast feeding. The objectives of the present study were ...

  8. The Incidence of Anabolic Steroid Use among Competitive Bodybuilders.

    ERIC Educational Resources Information Center

    Tricker, Ray; And Others

    1989-01-01

    Investigated incidence of anabolic steroid use among 380 competitive male and female bodybuilders in Kansas and Missouri. Results indicated more than half (54 percent) of the male bodybuilders were using steroids on a regular basis compared to 10 percent of the female competitors. Found main reason for use of steroids was desire to win. (Author/TE)

  9. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  10. Anabolic Steroid Use: Indications of Habituation among Adolescents.

    ERIC Educational Resources Information Center

    Yesalis, Charles E.; And Others

    1989-01-01

    Identified characteristics of adolescent male anabolic steroid (AS) user and addictive potential. Found AS user population different from nonuser in self-perceptions of health and strength, interest in controlling AS use, and perception of peer AS use. Found subgroups with significantly different attitudes and/or behaviors. Suggests prevention…

  11. Psychological Predictors of Anabolic Steroid Use: An Exploratory Study.

    ERIC Educational Resources Information Center

    Schwerin, Michael J.; Corcoran, Kevin J.; LaFleur, Bonnie J.; Fisher, Leslee; Patterson, David; Olrich, Tracy

    1997-01-01

    Examined social physique anxiety, upper body esteem, social anxiety, and body dissatisfaction as possible predictors of anabolic steroid (AS) use. Results based on 185 AS-using bodybuilders and various control groups indicated that the upper body strength subscale of two measures, along with age, were significant predictors of AS use. (RJM)

  12. Psychological and Behavioral Effects of Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Bahrke, Michael S.

    This review of the literature on the psychological and behavioral effects of anabolic-androgenic steroids (AS) first looks at aspects of the history and prevalence of AS use in competitive sports. Research suggests that one-quarter to one-half million adolescents in the United States have used, or are currently using AS. Some effects of androgens…

  13. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  14. Anabolic Steroid Use: Indications of Habituation among Adolescents.

    ERIC Educational Resources Information Center

    Yesalis, Charles E.; And Others

    1989-01-01

    Identified characteristics of adolescent male anabolic steroid (AS) user and addictive potential. Found AS user population different from nonuser in self-perceptions of health and strength, interest in controlling AS use, and perception of peer AS use. Found subgroups with significantly different attitudes and/or behaviors. Suggests prevention…

  15. Psychological Predictors of Anabolic Steroid Use: An Exploratory Study.

    ERIC Educational Resources Information Center

    Schwerin, Michael J.; Corcoran, Kevin J.; LaFleur, Bonnie J.; Fisher, Leslee; Patterson, David; Olrich, Tracy

    1997-01-01

    Examined social physique anxiety, upper body esteem, social anxiety, and body dissatisfaction as possible predictors of anabolic steroid (AS) use. Results based on 185 AS-using bodybuilders and various control groups indicated that the upper body strength subscale of two measures, along with age, were significant predictors of AS use. (RJM)

  16. The Incidence of Anabolic Steroid Use among Competitive Bodybuilders.

    ERIC Educational Resources Information Center

    Tricker, Ray; And Others

    1989-01-01

    Investigated incidence of anabolic steroid use among 380 competitive male and female bodybuilders in Kansas and Missouri. Results indicated more than half (54 percent) of the male bodybuilders were using steroids on a regular basis compared to 10 percent of the female competitors. Found main reason for use of steroids was desire to win. (Author/TE)

  17. The incidence of anabolic steroid use among competitive bodybuilders.

    PubMed

    Tricker, R; O'Neill, M R; Cook, D

    1989-01-01

    The purpose of this study was to determine the incidence of anabolic steroid use among competitive male and female bodybuilders in Kansas and Missouri. A profile was established for users and non-users of anabolic steroids. The results of this study indicated that more than half of the male bodybuilders (54%) were using steroids on a regular basis compared to 10 percent of the female competitors. The types of steroid used were investigated and revealed that on average, four different types of anabolic steroid were used during the year, with individual use ranging from one to fifteen different types; including Dianabol, Deca Durabolin, Anavar, Testosterone, Androl 50, Winstrol, Primobolan, Equipoise, Finaject, Parabolin, HCG, Primacetate, Enanthate, Halotestin, and Maxibolin, in order of the most to least frequently used. The female bodybuilders reported that they had used an average of two different steroids including Deca Durabolin, Anavar, Testosterone, Dianabol, Equipoise, and Winstrol. The principal reason bodybuilders used steroids was related to their perception that these drugs were an important factor in winning competitions. Another important motivating factor for use was consistent with reports that significant gains in strength could be achieved by including anabolic steroids as part of the training regimen in spite of the reported adverse side-effects.

  18. Bolus vs. continuous feeding to optimize anabolism in neonates

    USDA-ARS?s Scientific Manuscript database

    Neonates with feeding difficulties can be fed by orogastric tube, using either continuous or bolus delivery. This review reports on recent findings that bolus is advantageous compared to continuous feeding in supporting optimal protein anabolism. Whether bolus or continuous feeding is more beneficia...

  19. "Anabolic" effects of methandienone in men undergoing athletic training.

    PubMed

    Hervey, G R; Hutchinson, I; Knibbs, A V; Burkinshaw, L; Jones, P R; Norgan, N G; Levell, M J

    1976-10-02

    After failure to confirm an anabolic action of testosterone and its derivatives in rats, methandienone ('Dianabol', an "anabolic steroid" used by athletes) has been given to 11 athletic men during a course of weight-training, in a double-blind, crossover experiment. The dose of methandienone was 100 mg/day for 6 wk. Body weight and composition, muscular strength and performance, and indices of endocrine function were studied. Compared with the placebo period, on methandienone the subjects gained weight (mean 3-3 kg +/- 0-6 kg) and accumulated a disproportionately large amount of potassium (420+/-68 mmol); the increase in weight was confined to the lean part of the body, and the muscles increased in size. Strength and performance improved over each training period, but not significantly differently on drug and placebo. On the drug, plasma-cortisol concentration and urinary cortisol excretion increased, and plasma-testosterone decreased. Although the weight and body-composition changes may demonstrate an anabolic action of methandienone in man, they may alternatively have been caused by an increase in intracellular fluid, and the question of anabolic action therefore remains open.

  20. Human growth hormone doping in sport

    PubMed Central

    Saugy, M; Robinson, N; Saudan, C; Baume, N; Avois, L; Mangin, P

    2006-01-01

    Background and objectives Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. Methods Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. Results and conclusion The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half‐life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays. PMID:16799101

  1. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    PubMed

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  2. Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

    PubMed Central

    Herlitz, Leal C.; Markowitz, Glen S.; Farris, Alton B.; Schwimmer, Joshua A.; Stokes, Michael B.; Kunis, Cheryl; Colvin, Robert B.

    2010-01-01

    Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed ≥40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized. PMID:19917783

  3. Development of focal segmental glomerulosclerosis after anabolic steroid abuse.

    PubMed

    Herlitz, Leal C; Markowitz, Glen S; Farris, Alton B; Schwimmer, Joshua A; Stokes, Michael B; Kunis, Cheryl; Colvin, Robert B; D'Agati, Vivette D

    2010-01-01

    Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed > or =40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized.

  4. ACOG Committee Opinion No. 484: Performance enhancing anabolic steroid abuse in women.

    PubMed

    2011-04-01

    Anabolic steroids are composed of testosterone and other substances related to testosterone that promote growth of skeletal muscle, increase hemoglobin concentration, and mediate secondary sexual characteristics. These substances have been in use since the 1930s to promote muscle growth, improve athletic performance, and enhance cosmetic appearance. Although anabolic steroids are controlled substances, only to be prescribed by a physician, it is currently possible to obtain anabolic steroids illegally without a prescription. There are significant negative physical and psychologic effects of anabolic steroid use, which in women can cause significant cosmetic and reproductive changes. Anabolic steroid use can be addictive and, therefore, difficult to stop. Treatment for anabolic steroid abuse generally involves education, counseling, and management of withdrawal symptoms. Health care providers are encouraged to address the use of these substances, encourage cessation, and refer patients to substance abuse treatment centers to prevent the long-term irreversible consequences of anabolic steroid use.

  5. Androgenic anabolic steroid exposure during adolescence: Ramifications for brain development and behavior

    PubMed Central

    Cunningham, Rebecca L.; Lumia, Augustus R.; McGinnis, Marilyn Y.

    2013-01-01

    Puberty is a critical period for brain maturation that is highly dependent on gonadal sex hormones. Modifications in the gonadal steroid environment, via the use of anabolic androgenic steroids (AAS), have been shown to affect brain development and behavior. Studies in both humans and animal models indicate that AAS exposure during adolescence alters normal brain remodeling, including structural changes and neurotransmitter function. The most commonly reported behavioral effect is an increase in aggression. Evidence has been presented to identify factors that influence the effect of AAS on the expression of aggression. The chemical composition of the AAS plays a major role in determining whether aggression is displayed, with testosterone being the most effective. The hormonal context, the environmental context, physical provocation and the perceived threat during the social encounter have all been found to influence the expression of aggression and sexual behavior. All of these factors point toward an altered behavioral state that includes an increased readiness to respond to a social encounter with heightened vigilance, and enhanced motivation. This AAS-induced state may be defined as emboldenment. The evidence suggests that the use of AAS during this critical period of development may increase the risk for maladaptive behaviors along with neurological disorders. PMID:23274699

  6. Urinary detection of conjugated and unconjugated anabolic steroids by dilute-and-shoot liquid chromatography-high resolution mass spectrometry.

    PubMed

    Tudela, Eva; Deventer, Koen; Geldof, Lore; Van Eenoo, Peter

    2015-02-01

    Anabolic androgenic steroids (AAS) are an important class of doping agents. The metabolism of these substances is generally very extensive and includes phase-I and phase-II pathways. In this work, a comprehensive detection of these metabolites is described using a 2-fold dilution of urine and subsequent analysis by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The method was applied to study 32 different metabolites, excreted free or conjugated (glucuronide or sulfate), which permit the detection of misuse of at least 21 anabolic steroids. The method has been fully validated for 21 target compounds (8 glucuronide, 1 sulfate and 12 free steroids) and 18 out of 21 compounds had detection limits in the range of 1-10 ng mL(-1) in urine. For the conjugated compounds, for which no reference standards are available, metabolites were synthesized in vitro or excretion studies were investigated. The detection limits for these compounds ranged between 0.5 and 18 ng mL(-1) in urine. The simple and straightforward methodology complements the traditional methods based on hydrolysis, liquid-liquid extraction, derivatization and analysis by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Copyright © 2014 John Wiley & Sons, Ltd.

  7. Disruption of LRP6 in osteoblasts blunts the bone anabolic activity of PTH.

    PubMed

    Li, Changjun; Xing, Qiujuan; Yu, Bing; Xie, Hui; Wang, Weishan; Shi, Chenhui; Crane, Janet L; Cao, Xu; Wan, Mei

    2013-10-01

    Mutations in low-density lipoprotein receptor-related protein 6 (LRP6) are associated with human skeletal disorders. LRP6 is required for parathyroid hormone (PTH)-stimulated signaling pathways in osteoblasts. We investigated whether LRP6 in osteoblasts directly regulates bone remodeling and mediates the bone anabolic effects of PTH by specifically deleting LRP6 in mature osteoblasts in mice (LRP6 KO). Three-month-old LRP6 KO mice had a significant reduction in bone mass in the femora secondary spongiosa relative to their wild-type littermates, whereas marginal changes were found in femoral tissue of 1-month-old LRP6 KO mice. The remodeling area of the 3-month-old LRP6 KO mice showed a decreased bone formation rate as detected by Goldner's Trichrome staining and calcein double labeling. Bone histomorphometric and immumohistochemical analysis revealed a reduction in osteoblasts but little change in the numbers of osteoclasts and osteoprogenitors/osteoblast precursors in LRP6 KO mice compared with wild-type littermates. In addition, the percentage of the apoptotic osteoblasts on the bone surface was higher in LRP6 KO mice compared with wild-type littermates. Intermittent injection of PTH had no effect on bone mass or osteoblastic bone formation in either trabecular and cortical bone in LRP6 KO mice, whereas all were enhanced in wild-type littermates. Additionally, the anti-apoptotic effect of PTH on osteoblasts in LRP6 KO mice was less significant compared with wild-type mice. Therefore, our findings demonstrate that LRP6 in osteoblasts is essential for osteoblastic differentiation during bone remodeling and the anabolic effects of PTH. © 2013 American Society for Bone and Mineral Research.

  8. Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise.

    PubMed

    Apicella, Jenna M; Lee, Elaine C; Bailey, Brooke L; Saenz, Catherine; Anderson, Jeffrey M; Craig, Stuart A S; Kraemer, William J; Volek, Jeff S; Maresh, Carl M

    2013-03-01

    Our aim was to examine the effect of betaine supplementation on selected circulating hormonal measures and Akt muscle signaling proteins after an acute exercise session. Twelve trained men (age 19.7 ± 1.23 years) underwent 2 weeks of supplementation with either betaine (B) (1.25 g BID) or placebo (P). Following a 2-week washout period, subjects underwent supplementation with the other treatment (B or P). Before and after each 2-week period, subjects performed an acute exercise session (AES). Circulating GH, IGF-1, cortisol, and insulin were measured. Vastus lateralis samples were analyzed for signaling proteins (Akt, p70 S6k, AMPK). B (vs. P) supplementation approached a significant increase in GH (mean ± SD (Area under the curve, AUC), B: 40.72 ± 6.14, P: 38.28 ± 5.54, p = 0.060) and significantly increased IGF-1 (mean ± SD (AUC), B: 106.19 ± 13.45, P: 95.10 ± 14.23, p = 0.010), but significantly decreased cortisol (mean ± SD (AUC), B: 1,079.18 ± 110.02, P: 1,228.53 ± 130.32, p = 0.007). There was no difference in insulin (AUC). B increased resting Total muscle Akt (p = 0.003). B potentiated phosphorylation (relative to P) of Akt (Ser(473)) and p70 S6 k (Thr(389)) (p = 0.016 and p = 0.005, respectively). Phosphorylation of AMPK (Thr(172)) decreased during both treatments (both p = 0.001). Betaine (vs. placebo) supplementation enhanced both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis.

  9. Morphometric analysis of cortical bone upon the exposure to sustained delivery of anabolic promoting agents using adult male rats as a model.

    PubMed

    Tramontana, J; Benghuzzi, H; Tucci, M; Tsao, A; Hughes, J

    2001-01-01

    Several investigations have documented that the use of anabolic agents could promote osteogenesis and enhance bone ingrowth in traumatized bone. Previously, anabolic steroids have been shown to increase the mineralization of bone. However, their clinical use has been limited because of the unwanted virilizing activity. The previous studies used systemic administration of anabolic steroids, which subjects other tissues within the body to high concentrations of hormones. In addition, different anabolic/androgenic steroids have varying affinities to different cell types within tissues. The specific objectives of this study were (i) to histopathologically evaluate the structural changes associated with sustained delivery of testosterone (T), dihydrotestosterone (DHT), and androstendione (AED) using adult male rats as a model, and (ii) to morphometrically evaluate the cortical areas and length upon the exposure of the aforementioned hormones for 90 days. A total of 23 adult rats were randomly divided into five groups (group I = control, group II = sham, group III = AED, Group IV = T and group V = DHT treated). At the end of the treatments the animals were euthanized and the x-rays, blood, and bones were analyzed using standard laboratory protocols. Data obtained from this investigation revealed the following: (A) all treated femurs appeared healthy with no traumatic responses observed in comparison to control animals, (B) measurements of the inner perimeter of the bone on the endosteal side showed significant reduction in the androgen treated animals. This suggesting that the androgens caused increases in the cortical bone. The differences seen in the amount of reduction was in the following ease: T > DHT > AED. C) quantitative measurements of the cortical length showed slight increases in the cortical lengths in the androgen treated rats in comparison to the control.

  10. Multivariate optimization of a derivatisation procedure for the simultaneous determination of nine anabolic steroids by gas chromatography coupled with mass spectrometry.

    PubMed

    Hadef, Y; Kaloustian, J; Portugal, H; Nicolay, A

    2008-05-09

    The medical commission of the International Olympic Committee forbids the use of anabolic androgenic steroids to improve sporting performances. Nine anabolic steroids (androsterone (A), nandrolone, estradiol, testosterone propionate, nandrolone-17 propionate, dydrogesterone, testosterone, epitestosterone, boldenone) and alpha-cholestane as internal standard were studied by gas chromatography coupled with mass spectrometry (GC/MS). The derivatisation reagent employed for the derivatisation of anabolic steroids was a mixture of N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide and 2-mercaptoethanol (1000:2:6, v/w/v). Trimethylsilyl (TMS) derivatives were obtained. Anabolic steroids can be derivatised into one or two forms, mainly for androsterone into A-monoTMS and A-diTMS. The aim of this study was to research the optimization conditions of the derivatisation process (maximum yield of silylation reaction) of each anabolic steroid into only one form. A two-level factorial Doelhert design was used to determine the influence of different parameters and their interactions on each compound, thanks to response surface methodology. The parameters to be optimized were the reaction time and the temperature. The interaction "temperature-reaction time" is significant and has a positive effect on the improvement of the effectiveness of the derivatisation. Considering the large amount of information, often not convergent, a global desirability function was applied for multi-responses optimization. Thus, the optimized temperature and the reaction time of silylation were 85 degrees C and 24 min, respectively. Several GC/MS analytical parameters were also studied: linearity (regression coefficient upper than 0.99 for each compound, sensibility (range of concentration 0.05-0.30 microg/ml). Confirmatory experiments were applied to check the predicted values and to validate the model. The confirmatory assay responses are relatively close to the responses predicted

  11. Osteoporotic fracture and parathyroid hormone

    PubMed Central

    Datta, Nabanita S

    2011-01-01

    Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34), is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair. In spite of PTH’s clinical use, safety is a major consideration for long-term treatment. Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms. Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures. This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models. The ultimate goal of providing an alternative to PTH, currently the sole anabolic therapy in clinical use, to promote bone formation and improve bone strength in the aging population is yet to be achieved. PMID:22474638

  12. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites.

    PubMed Central

    Snyder, G D; Capdevila, J; Chacos, N; Manna, S; Falck, J R

    1983-01-01

    Anterior pituitary cells were incubated in the presence of luteinizing hormone-releasing hormone and one of three inhibitors of arachidonic acid metabolism:indomethacin, an inhibitor of the cyclooxygenase system; nordihydroguaiaretic acid, an antioxidant that inhibits lipoxygenase; and icosatetraynoic acid, an acetylenic analogue of arachidonic acid that blocks all known pathways of arachidonic acid metabolism. Indomethacin was ineffective in blocking luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Nordihydroguaiaretic acid was only marginally capable of inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Icosatetraynoic acid at 10 microM completely inhibited stimulated luteinizing hormone secretion. Addition of several epoxygenated arachidonic acid metabolites to cells in vitro resulted in secretion of luteinizing hormone equal to or greater than that induced by 10 nM luteinizing hormone-releasing hormone. The half-maximal effective dose for these compounds was approximately 50 nM. The 5,6-epoxyicosatrienoic acid was the most potent of the compounds tested. These studies suggest that luteinizing hormone-releasing hormone-stimulated luteinizing hormone release is closely coupled with the production of oxidized arachidonic acid metabolites. Moreover, one or more of the epoxygenated arachidonic acid metabolites might be a component of the cascade of reactions initiated by luteinizing hormone-releasing hormone that ultimately results in secretion of luteinizing hormone. PMID:6344087

  13. Hormone Therapy

    MedlinePlus

    ... of estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... of two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  14. Improved management of drugs, hormones and pesticides in Africa.

    PubMed

    Mitema, E S

    2009-03-01

    Drugs, hormones and pesticides are chemical compounds used for alleviation of various diseases in animals. There are many classes of drugs which have been used and in the case of natural steroid hormones these have been used to increase mass gain by stimulating protein anabolism. Pesticides have been used for many years in the control of ectoparasites which transmit important human and livestock diseases. The purpose of the present article is to review procedures for management of veterinary products to facilitate national and international trade. These compounds and/or their metabolites have the potential to cause undesirable health effects to either target animals or consumers. Most African countries do not have competent authorities to conduct risk analysis for veterinary drug and pesticide residues in edible tissues. Because of the possible undesirable health effects from residues of veterinary compounds, the FAO/WHO established expert groups to establish acceptable daily intake and maximum residue levels (MRLs) for each drug or pesticide. In the case of natural steroids like oestradiol, progesterone and testosterone implants, no withdrawal period is required since there is no risk to the consumer. Bulls can have levels of testosterone ranging from 535-10,950 pg/g, heifers 92-250 and treated steers 100 pg/g, respectively. Data to enable approval of drugs and pesticides is to a large extent similar and include toxicity studies, reproductive studies, stability studies, safety, efficacy, tissue residue depletion studies and environmental impact. Good practice in the use of acaricides as indicated on the label is inevitable so that residue levels of these compounds remain below the specified MRL. Enactment and enforcement of legislations by various countries for the control of registration, sale, distribution and usage of ethical products should be enforced including use of prescriptions by veterinarians. Good practice in the use of veterinary drugs is the

  15. Sample preparation for the determination of steroids (corticoids and anabolics) in feed using LC.

    PubMed

    Muñiz-Valencia, Roberto; Ceballos-Magaña, Silvia G; Gonzalo-Lumbreras, Raquel; Santos-Montes, Ana; Izquierdo-Hornillos, Roberto C

    2008-07-01

    An improved sample preparation procedure for the determination of 17 steroids (corticoids (CC) and androgenic anabolic steroids (AAS)), used potentially as growth promoters, in feed samples has been developed. This procedure is based on two reported LC-UV methods. The improved procedure includes a leaching process using ACN, saponification, and SPE using polymeric cartridges. The proposed method was validated according to the EU criteria established for quantitative screening methods in PFS. The extraction efficiencies, decision limits (CCalpha) and detection capabilities (CCbeta), for these compounds were in the ranges of 82-100%, 19-40, and 24-53 microg/kg, respectively. The repeatability and the within-laboratory reproducibility at 1.0, 1.5, and 2.0 CCbeta levels were smaller than 10%. Accuracy was in the 97-101% range. The robustness was evaluated using the Youden robustness test. This method was applied to the analysis of steroids in different kinds of FS with satisfactory results.

  16. Growth hormone abuse and bodybuilding as aetiological factors in the development of bilateral internal laryngocoeles. A case report.

    PubMed

    Moor, James W; Khan, M Iqbal J

    2005-07-01

    A 36-year-old man presented with hoarseness and stridor. He was an elite professional bodybuilder and admitted to having abusing anabolic steroids and growth hormone in the recent past. A CT scan showed bilateral laryngocoeles. The patient was initially managed with intravenous corticosteroids and broad-spectrum antibiotics, and the stridor resolved sufficiently to permit discharge from the hospital. He proceeded to undergo endoscopic marsupialisation of his laryngocoeles and to date has made a full recovery. This is the first reported case where anabolic steroid and growth hormone abuse combined with an elite bodybuilder's exercise regime has been implicated in the aetiology of bilateral laryngocoeles.

  17. IGF-1 and insulin as growth hormones.

    PubMed

    Laron, Zvi

    2004-01-01

    IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.

  18. Determination of anabolic steroids in human urine by automated in-tube solid-phase microextraction coupled with liquid chromatography-mass spectrometry.

    PubMed

    Saito, Keita; Yagi, Katsuharu; Ishizaki, Atsushi; Kataoka, Hiroyuki

    2010-09-05

    A simple, rapid and sensitive method was developed for determining the presence of seven anabolic steroids (boldenone, nandrolone, testosterone, methyltestosterone, epiandrosterone, androsterone, and atnozolol) in human urine. Glucuronide-conjugates of these compounds were hydrolyzed with beta-glucuronidase. The anabolic steroids were analyzed by on-line in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-mass spectrometry (LC-MS). The steroids were separated within 14 min by high performance liquid chromatography using a Chromolith RP-18e column and 5 mM ammonium formate/methanol (35/65, v/v) as a mobile phase at a flow rate of 1.0 mL/min. Electrospray ionization conditions in the positive ion mode were optimized for the MS detection of these compounds. The optimum in-tube SPME conditions were 20 draw/eject cycles with a sample size of 40 microL using a Supel-Q PLOT capillary column for the extraction. The extracted compounds could be desorbed readily from the capillary column by flow of the mobile phase, and no carryover was observed. Using the in-tube SPME LC-MS with SIM mode detection, good linearity of the calibration curve (r>0.995) was obtained in the concentration range of 0.5-20 ng/mL, except for stanozolol. The detection limits (S/N=3) of anabolic steroids were in the range 9-182 pg/mL and the proposed method showed 20-33-fold higher sensitivity than the direct injection method. The within-day and between-day precisions were below 4.0% and 7.3% (n=5), respectively. This method was applied successfully to the analysis of urine samples without the interference peaks. The recovery rates of anabolic steroids spiked into urine samples were above 85%. This method is useful to analyze the urinary levels of these compounds in anti-doping tests.

  19. Sensitive and robust method for anabolic agents in human urine by gas chromatography-triple quadrupole mass spectrometry.

    PubMed

    Delgadillo, Miguel A; Garrostas, Lorena; Pozo, Oscar J; Ventura, Rosa; Velasco, Benjamín; Segura, Jordi; Marcos, Josep

    2012-05-15

    A rapid, sensitive and robust gas chromatography-triple quadrupole mass spectrometry method was developed for the determination of seven anabolic agents in human urine. The selection of analytes includes the main metabolites of all anabolics with higher sensitivity requirements. After optimizing the fragmentation conditions for each compound, a validation procedure for qualitative analysis was performed. The selectivity of the method showed that no interfering peaks were observed at the retention time of the compound. Adequate intermediate precision, below 14%, was observed for all of the compounds at the lower concentration tested. The concentrations assayed were in accordance with the performance limits required by the World Anti-Doping Agency (WADA). Unlike a previously published GC/QqQ method, detection of 17α-methyl-5β-androstane-3α,17β-diol (the main metabolites of methyltestosterone) at 2 ng/mL was accomplished under routine conditions. The qualitative method was applied to the analysis of 1367 samples in the span of 2 weeks, as part of the doping control of the XVI Pan American Games which took place in Mexico (14th-30th October, 2011). The high sensitivity was maintained during the analysis of all analytical batches, proving for the first time the excellent ruggedness of GC/QqQ methods.

  20. Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

    PubMed

    Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

    2015-06-01

    Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected.

  1. Stevens-Johnson syndrome and abuse of anabolic steroids.

    PubMed

    Cocca, Serena; Viviano, Massimo

    2017-02-01

    Stevens-Johnson syndrome (SJS) is characterized by mucocutaneous tenderness and typical hemorrhagic erosions, erythema and epidermal detachment presenting as blisters and areas of denuded skin. SJS is often observed after drug use as well as after bacterial or viral infections. Several drugs are at high risk of inducing SJS, but there are no cases in the English literature regarding anabolic steroid use triggering SJS. In our paper, we describe a case in which use of anabolic androgenic steroids (AAS) was associated with SJS. The patient participated in competitive body-building and regularly took variable doses of AAS. Initial symptoms (headache, weakness, pharyngodynia, and fever) were ignored. After a week he presented to the Emergency Department with a burning sensation on the mouth, lips, and eyes. Painful, erythematous, maculopapular, and vesicular lesions appeared all over the body, including on the genitals. During hospitalization, he also developed a cardiac complication. The patient had not taken any drugs except AAS.

  2. ANABOLIC-ANDROGENIC STEROID DEPENDENCE? INSIGHTS FROM ANIMALS AND HUMANS

    PubMed Central

    Wood, Ruth I.

    2008-01-01

    Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system. PMID:18275992

  3. Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage.

    PubMed

    Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T

    2008-07-28

    Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

  4. Adverse effects of anabolic steroids in athletes. A constant threat.

    PubMed

    Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C

    2005-09-15

    Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.

  5. Anabolic-androgenic steroid dependence? Insights from animals and humans.

    PubMed

    Wood, Ruth I

    2008-10-01

    Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system.

  6. Stevens-Johnson syndrome and abuse of anabolic steroids

    PubMed Central

    2017-01-01

    Stevens-Johnson syndrome (SJS) is characterized by mucocutaneous tenderness and typical hemorrhagic erosions, erythema and epidermal detachment presenting as blisters and areas of denuded skin. SJS is often observed after drug use as well as after bacterial or viral infections. Several drugs are at high risk of inducing SJS, but there are no cases in the English literature regarding anabolic steroid use triggering SJS. In our paper, we describe a case in which use of anabolic androgenic steroids (AAS) was associated with SJS. The patient participated in competitive body-building and regularly took variable doses of AAS. Initial symptoms (headache, weakness, pharyngodynia, and fever) were ignored. After a week he presented to the Emergency Department with a burning sensation on the mouth, lips, and eyes. Painful, erythematous, maculopapular, and vesicular lesions appeared all over the body, including on the genitals. During hospitalization, he also developed a cardiac complication. The patient had not taken any drugs except AAS. PMID:28280713

  7. Anabolic and catabolic pathways regulating skeletal muscle mass

    PubMed Central

    McCarthy, John J.; Esser, Karyn A.

    2010-01-01

    Purpose of review the purpose of this review is to discuss recent findings as they pertain to anabolic and catabolic signaling pathways involved in the regulation of adult skeletal muscle mass. Recent findings research conducted over the past few years has continued to refine our understanding of the pathways that govern skeletal muscle mass, in particular the mTOR, FoxO and NF-κB pathways. Alternative signaling pathways have also emerged as important regulators of muscle mass such as the β-catenin pathway. Summary a better understanding of the anabolic and catabolic processes which regulate skeletal muscle mass is critical for the development of more effective therapeutics to prevent the loss of muscle with disuse, aging and disease. PMID:20154608

  8. The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism

    PubMed Central

    Chinnaiyan, Prakash; Kensicki, Elizabeth; Bloom, Gregory; Prabhu, Antony; Sarcar, Bhaswati; Kahali, Soumen; Eschrich, Steven; Qu, Xiaotao; Forsyth, Peter; Gillies, Robert

    2015-01-01

    Although considerable progress has been made toward understanding glioblastoma biology through large-scale genetic and protein expression analyses, little is known about the underlying metabolic alterations promoting their aggressive phenotype. We conducted global metabolomic profiling on patient-derived glioma specimens and identified specific metabolic programs differentiating low- and high-grade tumors, with the metabolic signature of glioblastoma reflecting accelerated anabolic metabolism. When coupled with transcriptional profiles, we identified the metabolic phenotype of the mesenchymal subtype to consist of accumulation of the glycolytic intermediate phosphoenolpyruvate and decreased pyruvate kinase activity. Unbiased hierarchical clustering of metabolomic profiles identified three subclasses, which we term energetic, anabolic, and phospholipid catabolism with prognostic relevance. These studies represent the first global metabolomic profiling of glioma, offering a previously undescribed window into their metabolic heterogeneity, and provide the requisite framework for strategies designed to target metabolism in this rapidly fatal malignancy. PMID:23026133

  9. Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage

    PubMed Central

    Martin, Nicole M; Dayyeh, Barham K Abu; Chung, Raymond T

    2008-01-01

    Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks. PMID:18680242

  10. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans.

    PubMed

    Berkenstam, Anders; Kristensen, Jens; Mellström, Karin; Carlsson, Bo; Malm, Johan; Rehnmark, Stefan; Garg, Neeraj; Andersson, Carl Magnus; Rudling, Mats; Sjöberg, Folke; Angelin, Bo; Baxter, John D

    2008-01-15

    Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.

  11. Anabolic androgenic steroids in delayed diagnosis of tuberculosis

    PubMed Central

    Upadhyaya, Suneet K.; Sharma, Archana; Rai, Deependra K.; Thawani, Vijay

    2012-01-01

    This is the first case report depicting masking of symptoms of intestinal tuberculosis by anabolic androgenic steroids (AAS) causing delay in diagnosis which lead to a major surgery. Negative tuberculosis skin test (TST) probably due to immunomodulating effects of AAS also contributed to the delay. Patient also had early dependence on AAS and rapid growth of scrotal sebaceous cysts, findings of which have not yet been reported. PMID:23326112

  12. Mineral catalyzed hydrothermal reactions as precursors to extant anabolic pathways

    NASA Astrophysics Data System (ADS)

    Cody, G. D.

    Investigations into hydrothermal reactions under conditions of moderate hydrostatic pressure and in the presence of transition metal sulfides reveal reaction pathways the bear remarkable similarity with extant anabolic reactions. First, it is seen that most common transition metal sulfides are capable of promoting all of the key reactions at the core of Acetyl Co-A synthesis. These include CO reduction to methyl groups and carbonyl insertion to form transferable acetyl groups. The synthesis of alpha-keto acids are also promoted, presumably by double carbonylation. A pathway starting with CO2 and H2 has been identified leading to the synthesis of citric acid. Citric acid provides a crucial abiotic, anabolic, branch point to the prebiotic synthesis of various amino acids, as well. As the pyrimidines, orotic acid and uracil. In many cases the abiotic reaction pathways differ slightly from extant anabolic pathways by shunting past particularly reactive intermediates, e.g. oxaloacetic acid. These reactions have the capacity to provide the prebiotic world with many, but not all, of the molecular constituents to aid the emergence of an RNA world.

  13. Effects of digoxin on the anabolic response to clenbuterol.

    PubMed

    Cartaña, J; Stock, M J

    1994-08-01

    The possible involvement of increased cation exchange in the anabolic response to the beta 2-selective adrenergic agonist clenbuterol was investigated using dietary admixtures of clenbuterol and the Na,K-adenosine triphosphatase (ATPase) inhibitor digoxin. In a rat feeding trial to assess the effects on body composition, it was found that the higher of two levels (5 and 30 mg/kg diet) of digoxin had an inhibitory effect on the repartitioning effects (ie, increased body weight and fat-free mass) of clenbuterol (2 mg/kg diet). In two further experiments using 30 and 60 mg digoxin/kg diet, it was found that the anabolic effects of clenbuterol on gastrocnemius muscle protein deposition were inhibited by digoxin, but the effects of clenbuterol on soleus muscle protein were more resistant to inhibition. Given the observed dose-dependent inhibition by digoxin of gastrocnemius muscle protein deposition in the three experiments, it was concluded that at least part of clenbuterol's anabolic actions on skeletal muscle may depend on increased Na,K-ATPase activity. However, different mechanisms or a different time course of Na,K-ATPase activation may occur in different muscle fiber types.

  14. Hormone abuse in sports: the antidoping perspective.

    PubMed

    Barroso, Osquel; Mazzoni, Irene; Rabin, Olivier

    2008-05-01

    Since ancient times, unethical athletes have attempted to gain an unfair competitive advantage through the use of doping substances. A list of doping substances and methods banned in sports is published yearly by the World Anti-Doping Agency (WADA). A substance or method might be included in the List if it fulfills at least two of the following criteria: enhances sports performance; represents a risk to the athlete's health; or violates the spirit of sports. This list, constantly updated to reflect new developments in the pharmaceutical industry as well as doping trends, enumerates the drug types and methods prohibited in and out of competition. Among the substances included are steroidal and peptide hormones and their modulators, stimulants, glucocorticosteroids, beta2-agonists, diuretics and masking agents, narcotics, and cannabinoids. Blood doping, tampering, infusions, and gene doping are examples of prohibited methods indicated on the List. From all these, hormones constitute by far the highest number of adverse analytical findings reported by antidoping laboratories. Although to date most are due to anabolic steroids, the advent of molecular biology techniques has made recombinant peptide hormones readily available. These substances are gradually changing the landscape of doping trends. Peptide hormones like erythropoietin (EPO), human growth hormone (hGH), insulin, and insulin-like growth factor I (IGF-I) are presumed to be widely abused for performance enhancement. Furthermore, as there is a paucity of techniques suitable for their detection, peptide hormones are all the more attractive to dishonest athletes. This article will overview the use of hormones as doping substances in sports, focusing mainly on peptide hormones as they represent a pressing challenge to the current fight against doping. Hormones and hormones modulators being developed by the pharmaceutical industry, which could emerge as new doping substances, are also discussed. 2008, Asian

  15. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  16. Androgenic, anabolic, estrogenic and antiestrogenic effects of desogestrel and lynestrenol: effects on serum proteins and vaginal cytology.

    PubMed

    Cullberg, G

    1984-07-01

    Eight healthy (apart from pelvic endometriosis) women were given daily doses of 0.125, 0.250 and 0.500 mg of desogestrel or 5 mg of lynestrenol orally in a randomized order. Duration of each treatment was 6 weeks. Serum was analyzed for sex hormone binding globulin (SHBG), ceruloplasmin, cortisol binding globulin (CBG), thyroxine binding globulin (TBG) and prealbumin using an electroimmunoassay. Serum 17 beta-estradiol (E2) and testosterone (T) were analyzed by radioimmunoassay. Vaginal cytology was studied using the maturation value (MV). E2 levels were depressed by desogestrel and lynestrenol apart from values in two women after 0.125 mg desogestrel. T concentration was suppressed by desogestrel but not by lynestrenol. SHBG concentration and MV were dose-dependently suppressed indicating an antiestrogenic or possibly androgenic effect of desogestrel and lynestrenol. No androgenic or anabolic effects of desogestrel were however seen, e.g. suppression of TBG content or increase in prealbumin levels. For lynestrenol, however, a small but significant increase in prealbumin concentration indicated a weak androgenic/anabolic effect. No estrogenic effects were seen, e.g. increases in ceruloplasmin, CBG levels or in elevations of MV. A depressed SHBG production ability in the hepatocytes during treatment with 19-nortestosterone derivatives is postulated, possibly due to competitive receptor binding.

  17. Feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization mass spectrometry in analyzing anabolic steroids in urine samples.

    PubMed

    Ahonen, Linda L; Haapala, Markus; Saarela, Ville; Franssila, Sami; Kotiaho, Tapio; Kostiainen, Risto

    2010-04-15

    We examined the feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization tandem mass spectrometry (capLC/microAPPI-MS/MS) for the analysis of anabolic steroids in human urine. The urine samples were pretreated by enzymatic hydrolysis (with beta-glucuronidase from Helix pomatia), and the compounds were liquid-liquid extracted with diethyl ether. After separation the compounds were vaporized by microchip APPI, photoionized by a 10 eV krypton discharge lamp, and detected by selected reaction monitoring. The capLC/microAPPI-MS/MS method showed good sensitivity with detection limits at the level of 1.0 ng mL(-1), good linearity with correlation coefficients between 0.9954 and 0.9990, and good repeatability with relative standard deviations below 10%. These results demonstrate that microchip APPI combined with capLC/MS/MS provides a new potential method for analyzing non-polar and neutral compounds in biological samples.

  18. Teriparatide Treatment Improves Bone Defect Healing Via Anabolic Effects on New Bone Formation and Non-Anabolic Effects on Inhibition of Mast Cells in a Murine Cranial Window Model.

    PubMed

    Zhang, Longze; Wang, Tao; Chang, Martin; Kaiser, Claire; Kim, Jason D; Wu, Tianyu; Cao, Xiaoyi; Zhang, Xinping; Schwarz, Edward M

    2017-09-01

    Investigations of teriparatide (recombinant parathyroid hormone [rPTH]) as a potential treatment for critical defects have demonstrated the predicted anabolic effects on bone formation, and significant non-anabolic effects on healing via undefined mechanisms. Specifically, studies in murine models of structural allograft healing demonstrated that rPTH treatment increased angiogenesis (vessels <30 μm), and decreased arteriogenesis (>30 μm) and mast cell numbers, which lead to decreased fibrosis and accelerated healing. To better understand these non-anabolic effects, we interrogated osteogenesis, vasculogenesis, and mast cell accumulation in mice randomized to placebo (saline), rPTH (20 μg/kg/2 days), or the mast cell inhibitor sodium cromolyn (SC) (24 μg/kg/ 2days), via longitudinal micro-computed tomography (μCT) and multiphoton laser scanning microscopy (MPLSM), in a critical calvaria defect model. μCT demonstrated that SC significantly increased defect window closure and new bone volume versus placebo (p < 0.05), although these effects were not as great as rPTH. Interestingly, both rPTH and SC have similar inhibitory effects on arteriogenesis versus placebo (p < 0.05) without affecting total vascular volume. MPLSM time-course studies in untreated mice revealed that large numbers of mast cells were detected 1 day postoperation (43 ± 17), peaked at 6 days (76 ± 6), and were still present in the critical defect at the end of the experiment on day 30 (20 ± 12). In contrast, angiogenesis was not observed until day 4, and functional vessels were first observed on 6 days, demonstrating that mast cell accumulation precedes vasculogenesis. To confirm a direct role of mast cells on osteogenesis and vasculogenesis, we demonstrated that specific diphtheria toxin-α deletion in Mcpt5-Cre-iDTR mice results in similar affects as SC treatment in WT mice. Collectively, these findings demonstrate that mast cells inhibit bone defect healing by

  19. A jaundiced bodybuilder Cholestatic hepatitis as side effect of injectable anabolic-androgenic steroids.

    PubMed

    Boks, Marije N; Tiebosch, Anton T; van der Waaij, Laurens A

    2017-11-01

    The use of anabolic steroids is prevalent in recreational athletes. This case report describes a young amateur bodybuilder who was referred to our outpatient clinic with jaundice and loss of appetite due to cholestatic hepatitis. Additional tests including a liver biopsy made it likely that the hepatitis was caused by the injectable anabolic steroid trenbolone enanthate. Cholestatic hepatitis may not be limited to the use of oral anabolic-androgenic steroids, as is widely assumed. Therefore, and because of other side effects, the recreational use of all forms of anabolic steroids should be discouraged.

  20. Pulmonary embolism associated with protein C deficiency and abuse of anabolic-androgen steroids.

    PubMed

    Alhadad, Alaa; Acosta, Stefan; Sarabi, Latif; Kölbel, Tilo

    2010-04-01

    We present the case of a 19-year-old male athlete with protein C deficiency who developed proximal deep venous thrombosis and pulmonary embolism while abusing anabolic-androgenic steroids. Anabolic-androgenic steroids have been reported to have anticoagulatory and profibrinolytic effects in patients with protein C deficiency. Despite these antithrombotic effects, the patient developed repeated venous thromboembolism during treatment with low-molecular-weight heparin. The net effect of anabolic-androgenic steroids on the haemostatic system may change from antithrombotic to prothrombotic in male abusers of anabolic steroids with protein C deficiency.

  1. [Successive ruptures of patellar and Achilles tendons. Anabolic steroids in competitive sports].

    PubMed

    Isenberg, J; Prokop, A; Skouras, E

    2008-01-01

    Derivatives of testosterone or of 19-nor-testosterone are used as anabolics for the purpose of improving performance although the effect of anabolics is known still to be under discussion. The use of anabolic steroids continues among competitive athletes despite increased controls and increasingly frequent dramatic incidents connected with them. Whereas metabolic dysfunction during anabolic use is well documented, ruptures of the large tendons are rarely reported. Within 18 months, a 29-year-old professional footballer needed surgery for rupture of the patellar tendon and of both Achilles tendons. Carefully directed questioning elicited confirmation that he had taken different anabolic steroids regularly for 3 years with the intention of improving his strength. After each operation anabolic steroids were taken again at a high dosage during early convalescence and training. Minimally invasive surgery and open suturing techniques led to complete union of the Achilles tendons in good time. Training and anabolic use (metenolon 300 mg per week) started early after suturing of the patellar tendon including bone tunnels culminated in histologically confirmed rerupture after 8 weeks. After a ligament reconstruction with a semitendinosus tendon graft with subsequent infection, the tendon and reserve traction apparatus were lost. Repeated warnings of impaired healing if anabolic use was continued had been given without success. In view of the high number of unrecorded cases in competitive and athletic sports, we can assume that the use of anabolic steroids is also of quantitative relevance in the operative treatment of tendon ruptures.

  2. Bioidentical Hormones and Menopause

    MedlinePlus

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Learn About Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ...

  3. Hormones and Obesity

    MedlinePlus

    ... Chemicals (EDCs) Endocrine Glands and Types of Hormones Brainy Hormones What Do Hormones Do? Infographics Myth vs ... Chemicals (EDCs) Endocrine Glands and Types of Hormones Brainy Hormones What Do Hormones Do? Infographics Myth vs ...

  4. Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats

    PubMed Central

    Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L.; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L.

    2013-01-01

    The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT-7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. PMID:23792034

  5. Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats.

    PubMed

    Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L

    2013-10-01

    The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT--7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory.

  6. Altered gonadal steroidogenesis in critical illness: is treatment with anabolic steroids indicated?

    PubMed

    Spratt, D I

    2001-12-01

    The physiology of the reproductive system changes dramatically with the onset of major illness. The serum testosterone concentrations fall to pre-pubertal levels secondary to a decreased secretion of gonadotropins and a decreased Leydig cell response to luteinizing hormone. At the same time, the serum oestrogen concentration rises as the result of an increased rate of peripheral aromatization. The clinical consequences of these marked changes are not yet well understood. One line of evidence argues for the administration of anabolic steroids (derivatives of testosterone) to critically ill patients to improve their catabolic state. Another line of evidence in animal models suggests that testosterone may suppress the immune system and myocardial function in critical illness. No clinical trials of oestrogen administration to critically ill patients have been reported, although two animal studies suggest that oestrogen may have a positive effect on survival. This chapter reviews changes in the physiology of the reproductive system in major illness as well as current evidence regarding the clinical effects of androgens and oestrogens in critical illness and their potential therapeutic roles.

  7. What can allostasis tell us about anabolic-androgenic steroid addiction?

    PubMed

    Hildebrandt, Tom; Yehuda, Rachel; Alfano, Lauren

    2011-08-01

    Anabolic-androgenic steroids (AASs) are synthetic hormones used by individuals who want to look better or perform better in athletics and at the gym. Their use raises an interesting paradox in which drug use is associated with a number of health benefits, but also the possibility of negative health consequences. Existing models of AAS addiction follow the traditional framework of drug abuse and dependence, which suggest that harmful use occurs as a result of the drug's ability to hijack the motivation-reward system. However, AASs, unlike typical drugs of abuse, are not used for acute intoxication effects or euphoria. Rather, AASs are used to affect the body through changes to the musculoskeletal system and the hypothalamic-pituitary-gonadal axis as opposed to stimulating the reward system. We offer an allostatic model of AAS addiction to resolve this inconsistency between traditional drug addiction and AAS addiction. This allostatic framework provides a way to (a) incorporate exercise into AAS misuse, (b) identify where AAS use transitions from recreational use into a drug problem, and (c) describe individual differences in vulnerability or resilience to AASs. Implications for this model of AAS addiction are discussed.

  8. Effects of anabolic androgenic steroids and social subjugation on behavior and neurochemistry in male rats.

    PubMed

    Frahm, Krystle A; Lumia, Augustus R; Fernandez, Elizabeth; Strong, Randy; Roberts, James L; McGinnis, Marilyn Y

    2011-01-01

    Early abuse and anabolic androgenic steroids (AAS) both increase aggression. We assessed the behavioral and neurochemical consequences of AAS, alone or in combination with social subjugation (SS), an animal model of child abuse. On P26, gonadally intact male rats began SS consisting of daily pairings with an adult male for 2 weeks followed by daily injections of the AAS, testosterone on P40. As adults, males were tested for sexual and aggressive behaviors towards females in various hormonal conditions and inter-male aggression in a neutral setting using home or opponent bedding. Neurotransmitter levels were assessed using HPLC. Results showed that AAS males displayed significantly more mounts toward sexually receptive, vaginally obstructed females (OBS) and displayed significantly more threats towards ovariectomized females. SS males mounted OBS females significantly less and were not aggressive toward females. The role of olfactory cues in a neutral setting did not affect aggression regardless of treatment. AAS significantly increased brainstem DOPAC and NE. SS decreased 5HIAA, DA, DOPAC, and NE in brainstem. 5HIAA was significantly increased in the prefrontal cortex of all experimental groups. We conclude that AAS and SS differentially affect behavior towards females as well as neurotransmitter levels.

  9. Urinary Concentrations of Steroids in Bulls under Anabolic Treatment by Revalor-XS® Implant

    PubMed Central

    Stella, Roberto; Barrucci, Federica; Lega, Francesca; Angeletti, Roberto

    2016-01-01

    Despite the European ban of using anabolics in food-producing animals, growth promoters might still be illegally used in the European Union. To control the food chain and guarantee consumers' health, there is a need of highly sensitive analytical methods for the identification of marker residues of such treatments. In the present study, a group of bulls (n = 16) received trenbolone acetate (200 mg) and estradiol (40 mg) by a commercial ear implant during a time range of 71 days, and a second group (n = 16) was kept for control. The aim of the research was to measure the residual urinary concentrations of the administered drugs (β-trenbolone and β-estradiol), their main metabolites (α-trenbolone and α-estradiol), and possible alterations of the urinary profile of other endogenous hormones metabolically related. The analytical method was based on liquid chromatography-tandem mass spectrometry. Results showed average urinary concentrations of α-trenbolone and α-estradiol during treatment in the range of (0.81 ÷ 2.1) ng mL−1 and (0.96 ÷ 4.4) ng mL−1, respectively, whereas β-trenbolone and β-estradiol exhibit urinary concentrations lower than 0.22 ng mL−1 in both cases. Data obtained from the urinary profiles of endogenous steroids indicate that they could be useful to indirectly detect the ongoing treatment. PMID:27840769

  10. Co-administration of antiresorptive and anabolic agents: a missed opportunity.

    PubMed

    Seeman, Ego; Martin, T John

    2015-05-01

    Co-administration of antiresorptive and anabolic therapies has appeal because these treatments target the two main abnormalities in bone remodeling responsible for bone loss and microstructural deterioration. Antiresorptives reduce the number of basic multicellular units (BMUs) remodeling bone and reduce the volume of bone each BMU resorbs. Intermittent parathyroid hormone (PTH) increases the volume of bone formed by existing BMUs and those generated by PTH administration. PTH also increases bone formation by stimulating the differentiation, maturation, and longevity of osteoblast lineage cells residing upon quiescent bone surfaces. Despite these rationally targeted actions, enthusiasm for this approach waned when combined therapy blunted the increase in areal bone mineral density (aBMD) relative to that produced by PTH. Although many studies have since reported additive effects of combined therapy, whatever the aBMD result (blunting, additive, or null), these outcomes give little, if any, insight into changes in bone's material composition or microstructure and give misleading information concerning the net effects on bone strength. Combined therapy remains a potentially valuable approach to therapy. Because studies of antifracture efficacy comparing combined with single therapy are unlikely to be performed in humans, efforts should be directed toward improving methods of quantifying the net effects of combined therapy on bone's material composition, microarchitecture, and strength. © 2015 American Society for Bone and Mineral Research.

  11. [Anabolic therapy of induced osteoporosis in beta-thalassaemia major: case report and literature review].

    PubMed

    Trotta, A; Corrado, A; Cantatore, F P

    2010-01-01

    Transfusion program and chelating therapy treatment has extended the life expectancy of thalassaemic patient; osteoporosis is considered an important cause of morbidity in adult patients who display increased fracture risk. This is a case report is about a thalassaemic young female with multiple spine fractures (D11, D12 e L2) and lumbar spine DEXA - T score = -3,1 and femoral = -3,4. This was in spite of therapy with alendronate 70 mg/week from January 2006 to September 2007. The patient was subsequentently treated for 18 months with 1-34 recombinant human parathyroid hormone and colecalciferol (100.000 U/monthly). After 4 months of therapy, the patient showed a decrease in spinal pain (Roland and Morris Disability Questionnaire) and an improvement of quality of life (Qualeffo) with normalization of osteocalcin and 25-OHcolecalciferol haematic levels after 6 months. Lumbar spine and femoral DEXA - Tscore, at 18 months, rose respectively to -2,5 and -2,4. Thalassaemia-induced osteoporosis is multifactorial and its management is very difficult. Bone marrow expansion, endocrine dysfunction, iron overload and genetic factors all seem to play important roles in the development of low bone mass in these patients. Bisphosfonates have been used in the management of thalassemia induced osteoporosis but there is no data about fracture risk. Anabolic therapy for thalassemic patients requests additional study on a large scale.

  12. Detecting growth hormone misuse in athletes

    PubMed Central

    Holt, Richard I. G.

    2013-01-01

    Athletes have been misusing growth hormone (GH) for its anabolic and metabolic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. Although there is an ongoing debate about whether GH is performance enhancing, recent studies suggest that GH improves strength and sprint capacity, particularly when combined with anabolic steroids. The detection of GH misuse is challenging because it is an endogenous hormone. Two approaches have been developed to detect GH misuse; the first is based on the measurement of pituitary GH isoforms and the ratio of 22-kDa isoform to total GH. The second is based on the measurement of insulin like growth factor-I (IGF-I) and N-terminal propeptide of type III procollagen (P-III-NP) which increase in a dose-dependent manner in response to GH administration. Both methodologies have been approved by the World Anti-Doping Agency (WADA) and have led to the detection of a number of athletes misusing GH. PMID:24251151

  13. OVERVIEW OF EXPOSURE TO DIOXIN-LIKE COMPOUNDS AND PCBS ON DEVELOPMENTAL, IMMUNOSUPPRESSIVE, AND HORMONE-RELATED EFFECTS IN MAMMALS, INCLUDING HUMANS

    EPA Science Inventory

    Exposure to TCDD and related compounds leads to a plethora of effects in multiple species, tissues and stages of development. The response spectrum ranges from simple biochemical alterations to overtly toxic responses, including lethality. Many of the effects of TCDD and relate...

  14. OVERVIEW OF EXPOSURE TO DIOXIN-LIKE COMPOUNDS AND PCBS ON DEVELOPMENTAL, IMMUNOSUPPRESSIVE, AND HORMONE-RELATED EFFECTS IN MAMMALS, INCLUDING HUMANS

    EPA Science Inventory

    Exposure to TCDD and related compounds leads to a plethora of effects in multiple species, tissues and stages of development. The response spectrum ranges from simple biochemical alterations to overtly toxic responses, including lethality. Many of the effects of TCDD and relate...

  15. Bilateral deltoid myositis ossificans in a weightlifter using anabolic steroids.

    PubMed

    Schultzel, Mark M; Johnson, Michael H; Rosenthal, Howard G

    2014-09-01

    A 40-year-old male weightlifter presented with a 6-month history of a painless mass in the right deltoid. He had no history of trauma to the shoulder other than an arthroscopic rotator cuff repair a few weeks earlier. Physical examination showed a firm, nontender mass located longitudinally and coinciding with the deltoid, measuring 12×14×4 cm. There was no limitation in range of motion or functioning. Magnetic resonance imaging (MRI) and computed tomography (CT) scans suggested a lobulated, heterogeneous mass with multiple areas of calcification that raised suspicion for soft tissue sarcoma vs myositis ossificans. Marginal resection of the soft tissue mass was performed, and pathologic studies confirmed the diagnosis of xanthogranulomatous myositis ossificans with dystrophic calcifications and central cystic degeneration. At 2-week follow-up, the patient had improved range of motion and pain, but he noted a second soft tissue mass in the left deltoid. The MRI and CT scans showed a 10.5×16×3.4-cm linear, lobulated lesion with multiple calcifications, similar in appearance to the contralateral deltoid. The patient admitted to frequently injecting anabolic steroids into his deltoids. Because the patient was asymptomatic on the left side and the MRI appearance of the left deltoid mass was similar to that of the myositis ossificans seen on the right side, the patient opted for nonsurgical treatment. This is a rare case of myositis ossificans occurring bilaterally in the deltoids after repeated injections of anabolic steroids. There is currently no known association between anabolic steroids and myositis ossificans. This condition often mimics malignant neoplasms, illustrating the necessity of resection for diagnostic confirmation. Copyright 2014, SLACK Incorporated.

  16. Psychological and physical impact of anabolic-androgenic steroid dependence.

    PubMed

    Ip, Eric J; Lu, Debbie H; Barnett, Mitchell J; Tenerowicz, Michael J; Vo, Justin C; Perry, Paul J

    2012-10-01

    To contrast the characteristics of two groups of anabolic-androgenic steroid (AAS) users-those with versus those without AAS dependence. Subanalysis of data from the Anabolic 500, a cross-sectional survey. One hundred twelve male AAS-dependent users and 367 AAS-nondependent users who completed an online survey between February 19 and June 30, 2009. Respondents were recruited from the Internet discussion boards of 38 fitness, bodybuilding, weightlifting, and steroid Web sites. The respondents provided online informed consent and completed the Anabolic 500, a 99-item Web-based survey. Self-reported data included demographics, exercise patterns, use of AAS and other performance-enhancing agents, adverse effects of AAS use, behavior consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for AAS dependence, history of illicit drug and alcohol use, history of sexual or physical abuse, and psychiatric conditions diagnosed according to the DSM-IV-TR. Behavior consistent with AAS dependence was identified in 23.4% of the survey participants. These AAS-dependent users were more excessive in their AAS use (e.g., higher doses, higher quantity of agents, longer duration of use), more likely to report a history of illicit heroin use in the last 12 months (5.4% vs 1.9%, p=0.049), and more likely to report a diagnosis of an anxiety disorder (16.1 vs 8.4%, p=0.020) or major depressive disorder (15.2% vs 7.4%, p=0.012) than AAS-nondependent users. Data from the Anabolic 500 survey showed that almost one quarter of AAS users were dependent on these drugs. These AAS-dependent users had a higher rate of heroin use as well as anxiety and major depressive disorders compared with AAS-nondependent users. These findings can help clinicians and researchers better understand and address the potential illicit drug use and psychiatric comorbidities that may be present among AAS-dependent users. © 2012 Pharmacotherapy

  17. Emerging anabolic agents in the treatment of osteoporosis.

    PubMed

    Lovato, Christina; Lewiecki, E Michael

    2017-08-04

    Osteoporosis is a common skeletal disease with serious consequences due to osteoporotic fractures and high costs to society for post-fracture care. Most patients at high risk for fracture are not receiving care to reduce fracture risk. The osteoporosis treatment gap has reached crisis proportions. Strategies to reduce the treatment gap include systematic methods for identifying and treating high risk patients, better education of patients and healthcare providers, better use of currently available drugs, and development of new drugs to treat osteoporosis. Areas covered: Two osteoanabolic agents with novel mechanisms of action have recently completed phase 3 clinical trials. The efficacy and safety findings of these studies are reviewed. Abaloparatide, a synthetic analog of parathyroid hormone-related protein, has received regulatory approval for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Romosozumab, a humanized monoclonal antibody to sclerostin, an endogenous inhibitor of bone formation, is under regulatory review. Expert opinion: Osteoanabolic therapy for osteoporosis can restore, at least in part, the degradation of bone microarchitecture that is a hallmark of this disease. The emergence of new osteoanabolic compounds expands the treatment options for patients at high risk for fracture.

  18. Hormonal regulators of muscle and metabolism in aging (HORMA): Design and conduct of a complex, double-masked, multicenter trial

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Older persons often lose muscle mass, strength, and physical function. This report describes the challenges of conducting a complex clinical investigation assessing the effects of anabolic hormones on body composition, physical function, and metabolism during aging. METHODS: HORMA is a m...

  19. Spatiotemporal variations in estrogenicity, hormones, and endocrine-disrupting compounds in influents and effluents of selected wastewater-treatment plants and receiving streams in New York, 2008-09

    USGS Publications Warehouse

    Baldigo, Barry P.; Phillips, Patrick J.; Ernst, Anne G.; Gray, James L.; Hemming, Jocelyn D.C.

    2014-01-01

    Endocrine-disrupting compounds (EDCs) in wastewater effluents have been linked to changes in sex ratios, intersex (in males), behavioral modifications, and developmental abnormalities in aquatic organisms. Yet efforts to identify and regulate specific EDCs in complex mixtures are problematic because little is known about the estrogen activity (estrogenicity) levels of many common and emerging contaminants. The potential effects of EDCs on the water quality and health of biota in streams of the New York City water supply is especially worrisome because more than 150 wastewater-treatment plants (WWTPs) are permitted to discharge effluents into surface waters and groundwaters of watersheds that provide potable water to more than 9 million people. In 2008, the U.S. Geological Survey (USGS), the New York State Department of Environmental Conservation (NYSDEC), New York State Department of Health (NYSDOH), and New York City Department of Environmental Protection (NYCDEP) began a pilot study to increase the understanding of estrogenicity and EDCs in effluents and receiving streams mainly in southeastern New York. The primary goals of this study were to document and assess the spatial and temporal variability of estrogenicity levels; the effectiveness of various treatment-plant types to remove estrogenicity; the concentrations of hormones, EDCs, and pharmaceuticals, personal care products (PPCPs); and the relations between estrogenicity and concentrations of hormones, EDCs, and PPCPs. The levels of estrogenicity and selected hormones, non-hormone EDCs, and PPCPs were characterized in samples collected seasonally in effluents from 7 WWTPs, once or twice in effluents from 34 WWTPs, and once in influents to 6 WWTPs. Estrogenicity was quantified, as estradiol equivalents, using both the biological e-screen assay and a chemical model. Results generally show that (1) estrogenicity levels in effluents varied spatially and seasonally, (2) a wide range of known and unknown EDCs

  20. Anabolic steroid use among students at a British college of technology.

    PubMed Central

    Williamson, D J

    1993-01-01

    To determine the rate of current or previous use of anabolic steroids by students at a UK college of technology, a questionnaire survey of 687 day students was conducted. The questionnaire began with a general section for all of the students, which ended with the question 'Have you ever used anabolic steroids?'. A further section specifically for anabolic steroid users examined patterns of use, and how certain circumstances might affect the individual's decision to use anabolic steroids. The response rate to the questionnaire was 92%. The overall rate of current or previous use of anabolic steroids was 2.8% (4.4% in males, 1.0% in females). Of these, 56% had first used anabolic steroids at age 15 or less. Anabolic steroid users were more likely to be male, under 17 years of age, and participating in bodybuilding, weight-lifting or rugby. The results of this survey, if confirmed in other groups of young people, would suggest that use of anabolic steroids may be widespread in the UK. PMID:8242280

  1. 76 FR 72355 - Classification of Two Steroids, Prostanozol and Methasterone, as Schedule III Anabolic Steroids...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... corticosteroids, treatment of delayed puberty in boys, treatment of metastatic breast cancer in women, and... stunted growth due to premature closure of the growth plates in long bones. In adolescent boys, anabolic steroid abuse can cause precocious sexual development. In both girls and women, anabolic steroid...

  2. Systemic lupus erythematosus with membranous glomerulonephritis and transverse myelitis associated with anabolic steroid use.

    PubMed

    Radis, C D; Callis, K P

    1997-10-01

    This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.

  3. Anabolic Steroids: A Threat to Body and Mind. National Institute on Drug Abuse Research Report Series.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    This report, based on findings of recent studies on the use of anabolic steroids in the United States, was written to educate the public about these drugs and the dangers of misusing them. It notes that the nonmedical use of anabolic/androgenic steroids among adolescents and young adults is of growing concern, with possibly as many as half a…

  4. Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

    PubMed

    Low, M S Y; Vilcassim, S; Fedele, P; Grigoriadis, G

    2016-04-01

    Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians. © 2016 Royal Australasian College of Physicians.

  5. Dissolved Organic Matter Assisted Transport of Hormones Through An Agricultural Soil

    NASA Astrophysics Data System (ADS)

    Jann, S.; Totsche, K. U.; Koegel-Knabner, I.; Schiffer, B.; Meyer, H. H. D.

    In the last years the disrupting activity of steroidal sex hormones like estrogens has been discussed for various ecosystems and even for human fertility. Once released into the environment, steroids pose a severe risk to fauna and man. After excretion of the relevant compounds or their metabolites by the target animals, the transition of biologically active substances via dung or manure onto soils and into the groundwa- ter cannot be excluded. Yet there is only little knowledge on the stability, degradation and transport pathways of steroids in soils. Just as little is known about the fate of anabolic steroids which are licensed as growth promotants for farm animals in many meat-exporting countries outside the EU (e.g. USA, Australia). We therefore studied the transport of Trenbolone-17 and Melengestrolacetate (MGA) with col- umn experiments employing aggregated agricultural field soil materials (Luvisol E and Bt horizons). The columns (14.6 cm in height, 4.7 cm in diameter) were perco- lated from bottom to top using a peristaltic pump. The mean volumetric flow rate was kept constant throughout the experiments at 20 ml h-1. Chloride was used as nonreac- tive tracer. The flow regime is controlled by two flow regions reflecting the dual mode pore size distribution of the aggregated soil material. Our results show that although the very high KOC values U Trenbolone: 24311 within the E-horizon; 21622 within the Bt-horizon and MGA: 16708 within the E-horizon; 59459 within the Bt horizon - we observe a quick breakthrough of low concentrations of the hormones simultaneous with the non-reactive tracer chloride. This points to the fact that within aggregated field soil, the risk for deep seepage of low concentrations of hormones is high.

  6. Steroid hormones control on nucleic acid biosynthesis in skeletal muscle.

    PubMed

    Burtea, C; Lefter, C; Butnaru, F; David, A

    1992-01-01

    The medical, agricultural and scientific interest of the muscular tissue is well established in the literature. Its formation and function are essential for survival. It is also known that steroid hormones are involved in the growth, development and maturation of skeletal muscles (sexual hormones) as well as in the process of body adjustment to the stress factors in the environment (glucocorticoid hormones). Starting from these considerations, our experiment has made an attempt to clarify part of the mechanisms involved in the action of steroid hormones at muscle level. On this purpose, 3H thymidine and 3H uridine incorporation was followed up in various types of skeletal muscles (femoral biceps, diaphragmatic, psoas) from rats treated with steroid hormones. Though known as anabolic hormones, sexual hormones did not induce significant and persistent changes in the nucleic acid synthesis (NAS), except for testosterone which enhanced RNA synthesis only in the level femoral muscle after 21 days of administration. Progesterone and the glucocorticoid hormones are known as hormones of proteic catabolism but it seems that this effect is more marked in muscles whose structure predominantly consists of white fibres (rapid muscles), as confirmed by our experiment.

  7. Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate*

    PubMed Central

    Thaler, Roman; Maurizi, Antonio; Roschger, Paul; Sturmlechner, Ines; Khani, Farzaneh; Spitzer, Silvia; Rumpler, Monika; Zwerina, Jochen; Karlic, Heidrun; Dudakovic, Amel; Klaushofer, Klaus; Teti, Anna; Rucci, Nadia; Varga, Franz; van Wijnen, Andre J.

    2016-01-01

    Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of the Tet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorption in vivo. Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis. PMID:26757819

  8. Modelling the anabolic response of bone using a cell population model.

    PubMed

    Buenzli, Pascal R; Pivonka, Peter; Gardiner, Bruce S; Smith, David W

    2012-08-21

    To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclastic lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone diseases. Several mathematical models of bone cell interactions have been developed, some including RANK-RANKL-OPG signalling between cells and systemic parathyroid hormone PTH. However, to our knowledge these models do not currently include key aspects of some more recent biological evidence for anabolic responses. In this paper, we further develop a mathematical model of bone cell interactions by Pivonka et al. (2008) to include the proliferation of precursor osteoblasts into the model. This inclusion is important to be able to account for Wnt signalling, believed to play an important role in the anabolic responses of bone. We show that an increased rate of differentiation to precursor cells or an increased rate of proliferation of precursor osteoblasts themselves both result in increased bone mass. However, modelling these different processes separately enables the new model to represent recent experimental discoveries such as the role of Wnt signalling in bone biology and the recruitment of osteoblast progenitor cells by transforming growth factor β. Finally, we illustrate the power of the new model's capabilities by applying the model to prostate cancer metastasis to bone. In the bone microenvironment, prostate cancer cells are believed to release some of the same signalling molecules used to coordinate bone remodelling (i.e.,Wnt and PTHrP), enabling the cancer cells to disrupt normal signalling and coordination between bone cells. This disruption can lead to either bone

  9. Hormones as doping in sports.

    PubMed

    Duntas, Leonidas H; Popovic, Vera

    2013-04-01

    Though we may still sing today, as did Pindar in his eighth Olympian Victory Ode, "… of no contest greater than Olympia, Mother of Games, gold-wreathed Olympia…", we must sadly admit that today, besides blatant over-commercialization, there is no more ominous threat to the Olympic games than doping. Drug-use methods are steadily becoming more sophisticated and ever harder to detect, increasingly demanding the use of complex analytical procedures of biotechnology and molecular medicine. Special emphasis is thus given to anabolic androgenic steroids, recombinant growth hormone and erythropoietin as well as to gene doping, the newly developed mode of hormones abuse which, for its detection, necessitates high-tech methodology but also multidisciplinary individual measures incorporating educational and psychological methods. In this Olympic year, the present review offers an update on the current technologically advanced endocrine methods of doping while outlining the latest procedures applied-including both the successes and pitfalls of proteomics and metabolomics-to detect doping while contributing to combating this scourge.

  10. [Body cult and use of anabolic steroids by bodybuilders].

    PubMed

    Iriart, Jorge Alberto Bernstein; Chaves, José Carlos; Orleans, Roberto Ghignone de

    2009-04-01

    This study focused on the reasons for practicing bodybuilding and the use of anabolic steroids, as well as the social representations and uses of the body among bodybuilding steroid users. This ethnographic study involved participant observation in middle and lower-class bodybuilding gyms in Salvador, Bahia State, Brazil, and 43 in-depth interviews with steroid users. Aesthetic reasons are the main motivation for bodybuilding and steroid use in both middle and lower-class users. Dissatisfaction with one's real body as compared to the ideal standard flaunted by the mass media, fear of being devalued or shunned by one's peer groups, the symbolic capital associated with a 'pumped-up' body, and the sense of immediacy in obtaining results all contributed to steroid use. Preventive campaigns are needed, targeting young people and combining a critical view and deconstruction of the values assigned to the body by consumer society, counteracted by high-quality information on the health risks associated with anabolic steroid use.

  11. Effects of anabolic-androgens on brain reward function

    PubMed Central

    Mhillaj, Emanuela; Morgese, Maria G.; Tucci, Paolo; Bove, Maria; Schiavone, Stefania; Trabace, Luigia

    2015-01-01

    Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. PMID:26379484

  12. Quo vadis plant hormone analysis?

    PubMed

    Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, Petr; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

    2014-07-01

    Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.

  13. Bioidentical Hormones and Menopause

    MedlinePlus

    ... Balance › Bioidentical Hormones and Menopause Fact Sheet Bioidentical Hormones and Menopause January, 2012 Download PDFs English Espanol ... take HT for symptom relief.) What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

  14. Growth Hormone

    MedlinePlus

    ... to help diagnose and monitor the treatment of acromegaly and gigantism . Growth hormone is essential for normal ... signs and symptoms of GH excess ( gigantism and acromegaly ). Suppression testing may be done when a pituitary ...

  15. Dioxin-like and perfluorinated compounds in pigs in an Indian open waste dumping site: toxicokinetics and effects on hepatic cytochrome P450 and blood plasma hormones.

    PubMed

    Watanabe, Michio X; Kunisue, Tatsuya; Tao, Lin; Kannan, Kurunthachalam; Subramanian, Annamalai; Tanabe, Shinsuke; Iwata, Hisato

    2010-07-01

    Dioxins and related compounds (DRCs) and perfluorinated compounds were measured in the livers of pigs (Sus scrofa) collected from an open waste dumping site in South India. Hepatic concentrations of DRCs and perfluorooctanesulfonate (PFOS; up to 200 ng/g wet wt) were significantly higher in male and female pigs, respectively, collected from the dumping site than in those from a reference site. Results suggest that dumping sites are a source of DRCs and PFOS. Hepatic concentrations of DRCs in piglets were higher than in mothers, especially for the congeners with molecular weights in the range of 360 to 400, implying congener-specific maternal transfer of DRCs in swine. Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans and some non-ortho dioxin-like polychlorinated biphenyls (PCBs) in the liver of pigs were higher than those in the adipose fat and muscle of the same specimens. In addition, the liver-to-adipose concentration ratios for each congener had a significant positive correlation with the levels of hepatic cytochrome P450 (CYP)1A-like protein, suggesting congener-specific and CYP1A-dependent hepatic sequestration of DRCs in the swine. Total hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs; 8.9-350 pg/g fat wt) had a significant positive correlation with CYP1A-like protein expression (r=0.56, p=0.012), suggesting the induction of CYP1A by DRCs. However, the total TEQs had a significant negative correlation with CYP4A-like protein (r=-0.49, p=0.029), suggesting repression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-mediated signaling pathway by DRCs. Decreases in plasma total thyroxine (T4), free T4, and immunoglobulin (Ig) G were also found in pigs from the dumping site compared with those from the reference site. This study provides insight into the toxicological impacts of DRCs and perfluorinated compounds in wild animals from open waste dumping sites.

  16. Determination of the prevalence of anabolic steroids, stimulants, and selected drugs subject to doping controls among elite sport students using analytical chemistry.

    PubMed

    Thevis, Mario; Sauer, Michael; Geyer, Hans; Sigmund, Gerd; Mareck, Ute; Schänzer, Wilhelm

    2008-08-01

    Drug abuse by adolescents has been investigated in various surveys that reported correlations between age, gender, and activity. However, none of these studies included chemical analyses to help substantiate the statements of participants. In the present study, the urine specimens of 964 students (439 females, 525 males; mean age 22.1 years, s = 1.7), who applied to study sports sciences at university, were assessed for anabolic steroids, stimulants, and selected drugs prohibited in sports. In total, 11.2% of the urine specimens provided contained drugs covered by doping controls. The most frequently detected compound was the major metabolite of tetrahydrocannabinol (9.8%) followed by various stimulants related to amphetamine and cocaine (1.0%). Indications of anabolic steroid use were found in 0.4% of urine samples but originated from contraceptives containing norethisterone. The present study provided unambiguous data on the status quo of drug (ab)use by adolescents hoping for a career related to elite sport or sports sciences. No use of anabolic steroids was detected. However, evidence for stimulants and tetrahydrocannabinol administration was obtained, although not reported by any participant, which highlights the issue of under-reporting in surveys based solely on questionnaires.

  17. Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

    PubMed

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2016-11-01

    Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age‐related anabolic resistance to exercise in humans

    PubMed Central

    Brook, Matthew S.; Wilkinson, Daniel J.; Mitchell, William K.; Lund, Jonathan N.; Phillips, Bethan E.; Szewczyk, Nathaniel J.; Greenhaff, Paul L.; Smith, Kenneth

    2016-01-01

    Key points Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age.Hypertrophic responses to RET with age are diminished compared to younger individuals.In response to 6 weeks RET, we found blunted hypertrophic responses with age are underpinned by chronic deficits in long‐term muscle protein synthesis.We show this is likely to be the result of multifactorial deficits in anabolic hormones and blunted translational efficiency and capacity.These results provide great insight into age‐related exercise adaptations and provide a platform on which to devise appropriate nutritional and exercise interventions on a longer term basis. Abstract Ageing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of ‘anabolic resistance’ in older humans. Twenty healthy male individuals, 10 younger (Y; 23 ± 1 years) and 10 older (O; 69 ± 3 years), performed 6 weeks unilateral RET (6 × 8 repetitions, 75% of one repetition maximum (1‐RM), 3 times per week). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom%; thereafter 50 ml week−1), further bilateral VL muscle biopsies were taken at 3 and 6 weeks to quantify muscle protein synthesis (MPS) via gas chromatography–pyrolysis–isotope ratio mass spectrometry. After RET, 1‐RM increased in Y (+35 ± 4%) and O (+25 ± 3%; P < 0.01), while MVC increased in Y (+21 ± 5%; P < 0.01) but not O (+6 ± 3%; not significant (NS)). In comparison to Y, O displayed blunted RET‐induced increases in muscle thickness (at 3 and 6 weeks, respectively, Y: +8 ± 1% and +11 ± 2%, P < 0.01; O: +2.6 ± 1% and +3.5 ± 2%, NS). While ‘basal’ longer term MPS was identical between Y and O (∼1.35 ± 0.1% day−1), MPS increased in response to RET only in Y (3 weeks, Y: 1.61 ± 0.1%

  19. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2013-07-01

    No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Anabolic androgen use in the management of hereditary angioedema: Not so cheap after all.

    PubMed

    Tse, Kevin Y; Zuraw, Bruce L; Chen, Qiaoling; Christiansen, Sandra C

    2017-04-01

    Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare, life-threatening disease that imposes a significant burden on affected patients. 17α-alkylated androgens (anabolic androgens) decrease attack frequency and severity but carry the risk of potentially serious dose-related adverse effects. Despite the emergence of targeted therapies for HAE, continued anabolic androgen use has been driven in part by their low cost. To examine the hidden cost of anabolic androgen use related to the risk of developing non-HAE comorbidities. Patients with HAE were identified in the Southern California Kaiser Permanente database using clinical and laboratory findings compatible with HAE. These patients were stratified into anabolic androgen exposed and nonexposed groups. Matched controls were selected from the Kaiser database who did not have HAE or anabolic androgen exposure. Using multivariate analysis, we determined the number of non-HAE comorbidities linked to anabolic androgen use. We next determined the association between dosing and increasing exposure to anabolic androgens and the likelihood of having various comorbidities. Patients with HAE exposed to anabolic androgens had a 28% increase (P = .04) in non-HAE comorbidities when compared with their matched (nonexposed) controls. With each gram per month increase in exposure, a 12% increase in non-HAE comorbidities is observed (P < .01). The most commonly occurring non-HAE comorbidities were psychiatric, muscle cramps, obesity, and hyperlipidemia. Our data suggest that long-term anabolic androgen use enhances the risk of developing comorbid health conditions, thus amplifying the cost of care. Our report provides additional support for the preferred use of newer, targeted therapies for the management of HAE. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

    PubMed

    Giannoulis, Manthos G; Martin, Finbarr C; Nair, K Sreekumaran; Umpleby, A Margot; Sonksen, Peter

    2012-06-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.

  2. Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

    PubMed Central

    Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

    2012-01-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established

  3. National Athletic Trainers' Association Position Statement: Anabolic-Androgenic Steroids

    PubMed Central

    Kersey, Robert D.; Elliot, Diane L.; Goldberg, Linn; Kanayama, Gen; Leone, James E.; Pavlovich, Mike; Pope, Harrison G.

    2012-01-01

    This NATA position statement was developed by the NATA Research & Education Foundation. Objective This manuscript summarizes the best available scholarly evidence related to anabolic-androgenic steroids (AAS) as a reference for health care professionals, including athletic trainers, educators, and interested others. Background Health care professionals associated with sports or exercise should understand and be prepared to educate others about AAS. These synthetic, testosterone-based derivatives are widely abused by athletes and nonathletes to gain athletic performance advantages, develop their physiques, and improve their body image. Although AAS can be ergogenic, their abuse may lead to numerous negative health effects. Recommendations Abusers of AAS often rely on questionable information sources. Sports medicine professionals can therefore serve an important role by providing accurate, reliable information. The recommendations provide health care professionals with a current and accurate synopsis of the AAS-related research. PMID:23068595

  4. Anabolic-androgenic steroid use among Brazilian bodybuilders.

    PubMed

    Nogueira, Fabiana Ranielle de Siqueira; Brito, Aline de Freitas; Oliveira, Caio Victor Coutinho de; Vieira, Thaiza Isidro; Gouveia, Rachel Linka Beniz

    2014-07-01

    This cross-sectional, quantitative, exploratory study investigated the prevalence and profile of anabolic-androgenic steroids (AAS) users amongst a convenience sample of 510 bodybuilders from 52 gyms, in João Pessoa, Brazil, with a structured questionnaire containing selected questions about socioeconomic and training variables on the use of AAS. Data were analyzed using frequency and chi-square tests. AAS prevalence use was 20.6%; mostly young men (98.1%), of a low education level (46.7%), who trained for more than 4 years (49.5%). The use of AAS was related to the use of dietary supplements. About 81% of consumed AAS consisted of Deca-Durabolin, Winstrol, and Sustanon. Study's limitations are noted.

  5. Epigenetic Regulation of Chondrocyte Catabolism and Anabolism in Osteoarthritis.

    PubMed

    Kim, Hyeonkyeong; Kang, Donghyun; Cho, Yongsik; Kim, Jin-Hong

    2015-08-01

    Osteoarthritis (OA) is one of the most prevalent forms of joint disorder, associated with a tremendous socioeconomic burden worldwide. Various non-genetic and lifestyle-related factors such as aging and obesity have been recognized as major risk factors for OA, underscoring the potential role for epigenetic regulation in the pathogenesis of the disease. OA-associated epigenetic aberrations have been noted at the level of DNA methylation and histone modification in chondrocytes. These epigenetic regulations are implicated in driving an imbalance between the expression of catabolic and anabolic factors, leading eventually to osteoarthritic cartilage destruction. Cellular senescence and metabolic abnormalities driven by OA-associated risk factors appear to accompany epigenetic drifts in chondrocytes. Notably, molecular events associated with metabolic disorders influence epigenetic regulation in chondrocytes, supporting the notion that OA is a metabolic disease. Here, we review accumulating evidence supporting a role for epigenetics in the regulation of cartilage homeostasis and OA pathogenesis.

  6. The metabolism of anabolic-androgenic steroids in the greyhound.

    PubMed

    McKinney, Andrew R; Cawley, Adam T; Young, E Bruce; Kerwick, Carmel M; Cunnington, Karen; Stewart, Rhiannon T; Ambrus, Joseph I; Willis, Anthony C; McLeod, Malcolm D

    2013-04-01

    Effective control of the use of anabolic-androgenic steroids (AASs) in animal sports is essential in order to ensure both animal welfare and integrity. In order to better police their use in Australian and New Zealand greyhound racing, thorough metabolic studies have been carried out on a range of registered human and veterinary AASs available in the region. Canine metabolic data are presented for the AASs boldenone, danazol, ethylestrenol, mesterolone, methandriol, nandrolone and norethandrolone. The principal Phase I metabolic processes observed were the reduction of A-ring unsaturations and/or 3-ketones with either 3α,5β- or 3β,5α-stereochemistry, the oxidation of secondary 17β-hydroxyl groups and 16α-hydroxylation. The Phase II β-glucuronylation of sterol metabolites was extensive. The presented data have enabled the effective analysis of AASs and their metabolites in competition greyhound urine samples.

  7. Anabolic steroid abuse and dependence in clinical practice.

    PubMed

    Brower, Kirk J

    2009-12-01

    The nonmedical use of anabolic-androgenic steroids (AAS) appeals to athletes across several sports, particularly those whose activity makes muscle size and strength advantageous, and in individuals (usually men) with body dysmorphic disorder. Patterns of nonmedical use, including supratherapeutic doses of illicitly obtained drugs, increase the risk for adverse psychiatric and other medical consequences. Although AAS users may be more likely to consult physicians for nonpsychiatric medical consequences than changes in their mental status, it is argued that the motivation for persistent use despite adverse consequences is sustained in large part by psychological variables. Therefore, all physicians who treat nonmedical AAS users will benefit from an understanding of these psychological variables, including the potential for AAS to cause dependence. This article aims to aid such understanding, and guidelines are suggested for assessment and treatment of nonmedical AAS users.

  8. Hepatic neoplasms associated with contraceptive and anabolic steroids.

    PubMed

    Ishak, K G

    1979-01-01

    This paper evaluates the differences between HCA (hepatocellular adenoma) and FNH (focal nodular hyperplasia) and the association of HCA and FNH with OC (oral contraceptives). FNH occurs at least twice as frequent in females as in males. A study conducted by the author revealed that only 20% of patients with FNH had symptoms and signs related to their neoplasms; in the rest, FNH was accidentally discovered during surgery for diseases of the gallbladder or at necropsy. The highly characteristic gross appearance of FNH is discribed in detail. The etiologic relationship between FNH and OC was cited in the light of frequent findings of FNH in infants and children, and of suggestions by other authors that FNH could be a direct result on OC therapy or that contraceptive steroids or conjugated estrogens accelerate the growth of FNH, a very slow growing neoplasm. Simple excision is the treatment of choice for FNH; in some cases, hepatic artery ligation is indicated. In the case of HCA, statistics show that the incidence of HCA has been increasing since 1960. Majority of patients with HCA have normal tests of hepatic function. Radiographic studies and hepatic scans may reveal HCA, but the best diagnostic method so far is angiography. Although gross appearance of HCA is variable, the features are clearly distinguishable from that of FNH. Other topics discussed include the occasional occurence of nodular regenerative hyperplasia in patients on OC or anabolic steroids (AS), and malignant liver tumors in patients using OC or AS. Further research should be done to clarify the etiologic relationship between androgenic-anabolic steroids and hepatocellular tumors and tumorlike lesions.

  9. Anabolic steroids and male infertility: a comprehensive review.

    PubMed

    de Souza, Guilherme Leme; Hallak, Jorge

    2011-12-01

    What's known on the subject? and What does the study add? The negative impact of AAS abuse on male fertility is well known by urologists. The secondary hypogonadotropic hypogonadism is often highlighted when AAS and fertility are being discussed. On the other hand, the patterns of use, mechanisms of action and direct effects over the testicle are usually overseen. The present study reviews the vast formal and "underground" culture of AAS, as well as their overall implications. Specific considerations about their impact on the male reproductive system are made, with special attention to the recent data on direct damage to the testicle. To our knowledge this kind of overview is absolutely unique, offering a distinguished set of information to the day-by-day urologists. For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. Initially, these substances were restricted to professional bodybuilders, becoming gradually more popular among recreational power athletes. Currently, as many as 3 million anabolic-androgenic steroids (AAS) users have been reported in the United States, and considering its increasing prevalence, it has become an issue of major concern. Infertility is defined as the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse, with male factor being present in up to 50% of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS, specially oriented to urologists, is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient axial inhibition, and the more recent experimental reports

  10. Anabolic Steroid Abuse among Teenage Girls: An Illusory Problem?

    PubMed Central

    Kanayama, Gen; Boynes, Matthew; Hudson, James I.; Field, Alison E.; Pope, Harrison G.

    2007-01-01

    Background Recent media reports have portrayed an alarming increase in apparent anabolic-androgenic steroid (AAS) use among American teenage girls; Congress even held hearings on the subject in June 2005. We questioned whether AAS use among teenage girls was as widespread as claimed. Methods We reviewed four large national surveys and many smaller surveys examining the prevalence of AAS use among teenage girls. Virtually all of these surveys used anonymous questionnaires. We asked particularly whether the language of survey questions might generate false-positive responses among girls who misinterpreted the term “steroid.” We also reviewed data from other countries, together with results from the only recent study (to our knowledge) in which investigators personally interviewed female AAS users. Results The surveys produced remarkably disparate findings, with the lifetime prevalence of AAS use estimated as high as 7.3% among ninth-grade girls in one study, but only 0.1% among teenage girls in several others. Upon examining the surveys reporting an elevated prevalence, it appeared that most used questions that failed to distinguish between anabolic steroids, corticosteroids, and over-the-counter supplements that respondents might confuse with “steroids.” Other features in the phrasing of certain questions also seemed likely to further bias results in favor of false-positive responses. Conclusions Many anonymous surveys, using imprecise questions, appear to have greatly overestimated the lifetime prevalence of AAS use among teenage girls; the true lifetime prevalence may well be as low as 0.1%. Future studies can test this impression by using a carefully phrased question regarding AAS use. PMID:17127018

  11. Caution for anabolic androgenic steroid use: a case report of multiple organ dysfunction syndrome.

    PubMed

    Unai, Shinya; Miessau, Joseph; Karbowski, Pawel; Baram, Michael; Cavarocchi, Nicholas C; Hirose, Hitoshi

    2013-12-01

    We report a 42-year-old male amateur body builder and user of anabolic androgenic steroids, who developed ARDS, acute kidney injury, and refractory supraventricular tachycardia. He required extracorporeal membrane oxygenation, continuous veno-venous hemodialysis, and catheter ablation. We believe that long-term anabolic androgenic steroid abuse predisposed the patient to multiple organ dysfunction syndrome, from its immunomodulatory effects in an otherwise healthy patient. Anabolic androgenic steroid use should be part of the history taking process, since it may complicate diagnosis, disease progression, and prognosis.

  12. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls.

  13. Low-magnitude whole-body vibration does not enhance the anabolic skeletal effects of intermittent PTH in adult mice.

    PubMed

    Lynch, Michelle A; Brodt, Michael D; Stephens, Abby L; Civitelli, Roberto; Silva, Matthew J

    2011-04-01

    Whole-body vibration (WBV) is a low-magnitude mechanical stimulus that may be anabolic for bone, yet we recently found that WBV did not improve bone properties in adult mice. Because intermittent parathyroid hormone (PTH) enhances the anabolic effects of high-magnitude skeletal loading, we sought to determine the skeletal effects of WBV in combination with PTH. Seven-month-old male BALB/c mice were assigned to six groups (n = 13-14/group) based on magnitude of applied acceleration (0 or 0.3 G) and PTH dose (0, 10, or 40 µg/kg/day). Mice were exposed to WBV (0.3 G, 90 Hz, sine wave) or sham loading (0 G) for 15 min/day, 5 days/week for 8 weeks. Vehicle or hPTH (1-34) was administered prior to each WBV session. Whole-body bone mineral content increased by ~ 5% from 0 to 8 weeks in the 40 µg/kg PTH group only, independent of WBV loading. Similarly, PTH treatment increased tibial cortical bone volume by ~5% from 0 to 8 weeks, independent of WBV loading. Neither PTH nor WBV stimulated trabecular bone formation. Consistent with the cortical bone effect, tibias from the 40 µg/kg PTH group had significantly greater ultimate force and energy to failure than tibias in the 0 and 10 µg/kg PTH groups, independent of WBV treatment. In summary, 8 weeks of intermittent PTH treatment increased cortical bone volume and strength in adult male BALB/c mice. Daily exposure to low-magnitude WBV by itself did not improve skeletal properties and did not enhance the PTH effect. No WBV-PTH synergy was found in this preclinical study. Copyright © 2010 Orthopaedic Research Society.

  14. Interactions between opioids and anabolic androgenic steroids: implications for the development of addictive behavior.

    PubMed

    Nyberg, Fred; Hallberg, Mathias

    2012-01-01

    Over the past decades, research on doping agents, such as anabolic androgenic steroids (AAS), has revealed that these compounds are often used in combination with other drugs of abuse. It seems that misuse of AAS probably involves more than a desire to enhance appearance or sports performance and studies have revealed that steroids are commonly connected with alcohol, opioids, tobacco, and psychotropic drugs. We have observed that AAS may interact with the endogenous opioids, excitatory amino acids, and dopaminergic pathways involved in the brain reward system. Furthermore, our studies provide evidence that AAS may induce an imbalance in these signal systems leading to an increased sensitivity toward opioid narcotics and central stimulants. In fact, studies performed in various clinics have shown that individuals taking AAS are likely to get addicted to opioids like heroin. This chapter reviews current knowledge on interactions between AAS and endogenous as well as exogenous opioids based not only on research in our laboratory but also on research carried out by several other clinical and preclinical investigators.

  15. Hormonal control of aging in rodents: The somatotropic axis

    PubMed Central

    Brown-Borg, Holly M.

    2015-01-01

    There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals. PMID:18674587

  16. The Availability and Acquisition of Illicit Anabolic Androgenic Steroids and Testosterone Preparations on the Internet.

    PubMed

    McBride, J Abram; Carson, Culley C; Coward, Matt

    2016-05-11

    The lifetime prevalence of anabolic androgenic steroids (AAS) use in the United States is over 1%. Recent reports have suggested AAS can easily be obtained over the Internet without a prescription, but this has been poorly studied. This study focused on determining the availability and ease of purchase for AAS, testosterone, and other non-AAS therapies on the Internet from the perspective of a typical consumer. A Google search was performed and the top-ranking sites offering AAS for sale were individually evaluated for selection of AAS offered, the purchasing process, and additional consumer information to support AAS use. The current results revealed that 87% of sites offered commonly used forms of AAS, injectable testosterone, and non-AAS hormone therapies. Seventy-five percent offered at least one postcycle recovery agent and 62% offered at least one erectile dysfunction medication. No site required a prescription for purchase of any substance, 75% accepted common forms of payment including credit card, and all sites were supplied by unregulated international pharmacies providing shipment to home addresses with disclaimers that consumers are liable to local laws. Seventy-five percent of sites provided specific cycle and stacking recommendations, 62% provided postcycle recovery information, but only one site offered information on non-AAS alternatives. In conclusion, AAS, injectable testosterone, and other non-AAS therapies are readily available and remarkably easy to purchase on the Internet without a prescription. It is of paramount importance that clinicians are aware of this considerable public health problem given the detrimental physiologic effects including infertility and sexual dysfunction. © The Author(s) 2016.

  17. Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters.

    PubMed

    Salas-Ramirez, Kaliris Y; Montalto, Pamela R; Sisk, Cheryl L

    2008-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone used by over half a million adolescents in the United States for their tissue-building potency and performance-enhancing effects. AAS also affect behavior, including reports of heightened aggression and changes in sexual libido. The expression of sexual and aggressive behaviors is a function of complex interactions among hormones, social context, and the brain, which is extensively remodeled during adolescence. Thus, AAS may have different consequences on behavior during adolescence and adulthood. Using a rodent model, these studies directly compared the effects of AAS on the expression of male sexual and aggressive behaviors in adolescents and adults. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or in adulthood (63-77 days of age). The day after the last injection, males were tested for either sexual behavior with a receptive female or agonistic behavior with a male intruder. Adolescent males treated with AAS showed significant increases in sexual and aggressive behaviors relative to vehicle-treated adolescents. In contrast, AAS-treated adults showed significantly lower levels of sexual behavior compared with vehicle-treated adults and did not show heightened aggression. Thus, adolescents, but not adults, displayed significantly higher behavioral responses to AAS, suggesting that the still-developing adolescent brain is more vulnerable than the adult brain to the adverse consequences of AAS on the nervous system and behavior.

  18. A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts

    PubMed Central

    Swarnkar, Gaurav; Sharan, Kunal; Siddiqui, Jawed A; Mishra, Jay Sharan; Khan, Kainat; Khan, Mohd Parvez; Gupta, Varsha; Rawat, Preeti; Maurya, Rakesh; Dwivedi, Anil K; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2012-01-01

    BACKGROUND AND PURPOSE Naringenin and its derivatives have been assessed in bone health for their oestrogen-‘like’ effects but low bioavailability impedes clinical potential. This study was aimed at finding a potent form of naringenin with osteogenic action. EXPERIMENTAL APPROACH Osteoblast cultures were harvested from mouse calvaria to study differentiation by naringenin, isosakuranetin, poncirin, phloretin and naringenin-6-C-glucoside (NCG). Balb/cByJ ovariectomized (OVx) mice without or with osteopenia were given naringenin, NCG, 17β-oestradiol (E2) or parathyroid hormone (PTH). Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labelling of bone. Plasma levels of NCG and naringenin were determined by HPLC. KEY RESULTS NCG stimulated osteoblast differentiation more potently than naringenin, while isosakuranetin, poncirin or phloretin had no effect. NCG had better oral bioavailability than naringenin. NCG increased the mRNA levels of oestrogen receptors (ERs) and bone morphogenetic protein (an ER responsive gene) in vivo, more than naringenin. In OVx mice, NCG treatment in a preventive protocol increased bone formation rate (BFR) and improved trabecular microarchitecture more than naringenin or E2. In osteopenic mice, NCG but not naringenin, in a therapeutic protocol, increased BFR and improved trabecular microarchitecture, comparable with effects of PTH treatment. Stimulatory effects of NCG on osteoblasts were abolished by an ER antagonist. NCG transactivated ERβ but not ERα. NCG exhibited no uterine oestrogenicity unlike naringenin. CONCLUSIONS AND IMPLICATIONS NCG is a potent derivative of naringenin that has bone anabolic action through the activation of osteoblast ERs and exhibited substantial oral bioavailability. PMID:21864313

  19. Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases.

    PubMed

    Fabresse, Nicolas; Grassin-Delyle, Stanislas; Etting, Isabelle; Alvarez, Jean-Claude

    2017-07-01

    We developed and validated a method to detect and quantify 12 anabolic steroids in blood (androstenedione, dihydrotestosterone, boldenone, epitestosterone, mesterolone, methandienone, nandrolone, stanozolol, norandrostenedione, tamoxifene, testosterone, trenbolone) and eight more in hair samples (nandrolone phenylpropionate, nandrolone decanoate, testosterone propionate, testosterone benzoate, testosterone cypionate, testosterone decanoate, testosterone phenylpropionate, testosterone undecanoate) using liquid chromatography coupled to high-resolution mass spectrometry. This method used a benchtop Orbitrap mass spectrometer operating with an APCI probe under positive ionization mode. Analysis was realized in full scan experiment with a nominal resolving power of 140,000. After addition of the internal standard (testosterone-D3) and incubation in phosphate buffer pH = 5 for hair, 200 μL of blood and 30 mg of hair samples were extracted with heptane. LOQ and LOD were determined at 5 and 1 ng mL(-1) in whole blood and 10 to 100 pg mg(-1) and 2 to 20 pg mg(-1) in hair according to the compounds, respectively. The method was linear in the 5-1000 ng mL(-1) range in whole blood and between 10 or 100 pg mg(-1) and 1000 pg mg(-1) in hair with correlation coefficients >0.99, and intra- and inter-day accuracy and precision were <14.8% for all compounds except for some esters in hairs (<19.9%) probably due to an important matrix effect for these compounds. This sensitive and specific method to detect anabolic steroids has been successfully applied to two real cases, for which various anabolic steroids in whole blood, urine, and hair were identified and quantified.

  20. Hormone impostors

    SciTech Connect

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  1. Improved ultrasonic-based sample treatment for the screening of anabolic steroids by gas chromatography/mass spectrometry.

    PubMed

    Galesio, M; Rial-Otero, R; Simal-Gándara, J; de la Torre, X; Botrè, F; Capelo-Martínez, J L

    2010-08-30

    A rapid sample treatment procedure for the gas chromatography/mass spectrometry (GC/MS) determination of anabolic steroids in human urine has been developed. The new procedure makes use of ultrasonic energy to reduce reaction times and increase the overall sensitivity. The following variables affecting the performance of the ultrasonic treatment were optimised: (i) time, (ii) device, (iii) frequency, and (iv) temperature. It was found that, under an ultrasonic field, the hydrolysis of conjugated steroids with beta-glucuronidase from Escherichia coli K12 was possible with a treatment time of 10 min. The accuracy and precision of the ultrasonic method were found to be in agreement with those achieved with the conventional thermal conductivity procedure (Student's t-test; p = 0.05, n = 10). After the enzymatic hydrolysis, the derivatisation of the target compounds with trimethylsilyl (TMS) reagent, methyl-N-trimethylsilyltrifluoroacetamide (MSTFA)/NH(4)I/dithioerythritol (DTE) (1000:2:4, v/w/w), was also accelerated using ultrasonic energy. In order to test the applicability of the use of ultrasonic energy in the acceleration of the derivatisation reaction with TMS, the classic method of thermal conductivity was applied for comparative purposes to a pool of 35 androgenic anabolic steroids (AAS) and/or their metabolites. The results demonstrated that after 3 min of sonication in a Sonoreactor device (50% amplitude), 19 of the 35 compounds studied showed similar reaction yield to those obtained with the classic procedure requiring 30 min (Student's t-test; p = 0.05, n = 5); 13 increased to higher silylation yields; and for the steroids 1-testosterone, danazol and etiocholanolone-D5, the same results were obtained using a sonication time of 5 min.The overall applicability of the ultrasonic-based sample treatment method is shown by the analysis of five urine samples. The results are similar to those achieved by the routine procedure. The new method is fast, robust, and

  2. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  3. [Effect of an anabolic steroid on the cellular immunity and postoperative evaluation of uterine cervical cancer].

    PubMed

    Ooshika, Y; Umesaki, N; Sako, H; Kawabata, M; Sugana, T

    1984-10-01

    The effects of an anabolic steroid on the immune activity and clinical condition of patients with cancer of the uterine cervix were studied. The effects of the steroid on tumor growth were also studied in animals. The results obtained demonstrated that the anabolic steroid (1) enhanced the activity of macrophages and cell-mediated immune activity, (2) reduced the incidence of post-operative infection, (3) reduced pose-operative loss of weight of patients due to the intrinsic anabolic activity of the steroid, and (4) did not exert any influence on tumor growth. Judging from these results, administration of the anabolic steroid would appear to be effective for the improvement of the general condition of cancer patients following surgery or in terminal cases.

  4. Use of anabolic-androgenic steroids among body builders--frequency and attitudes.

    PubMed

    Lindström, M; Nilsson, A L; Katzman, P L; Janzon, L; Dymling, J F

    1990-06-01

    A total of 138 male body builders who regularly attended a gym participated anonymously in a study of the use of anabolic-androgenic steroids in relation to side-effects, blood pressure, body mass index (BMI; kg m-2), training frequency, social background, occupation, knowledge and attitudes to steroid use. Fifty-three of the 138 body builders had used anabolic-androgenic steroids for a median duration of 2 years. Steroid use was linked to a higher BMI and more frequent training. Seventy-five per cent (n = 18) of those attending body building for competition, and 24% (n = 11) of those attending to improve their sense of well-being, used anabolic-androgenic steroids. Of all body builders, 94% considered anabolic-androgenic steroids to be dangerous. Of the users, 81% experienced side-effects, but 74% still intended to continue steroid medication.

  5. Anabolic Steroids: Metabolism, Doping and Detection in Human and Equestrian Sports

    NASA Astrophysics Data System (ADS)

    Kicman, A. T.; Houghton, E.; Gower, D. B.

    This chapter highlights the important aspects of detection of doping with synthetic anabolic steroids and discusses some of the problems with, and solutions to, the detection of misuse of the naturally occurring ones.

  6. The Use and Abuse of Anabolic Steroids: A Discussion for Health and Physical Education Teachers

    ERIC Educational Resources Information Center

    Thomas, John A.; And Others

    1973-01-01

    This article reviews research on anabolic steroids, indicating that athletes are mistaken in believing that taking them will improve their physical performance. Dangerous side-effects are also discussed. (JA)

  7. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  8. Acute hereditary coproporphyria induced by the androgenic/anabolic steroid methandrostenolone (Dianabol).

    PubMed

    Lane, P R; Massey, K L; Worobetz, L J; Jutras, M N; Hull, P R

    1994-02-01

    Acute attacks of porphyria can be induced by certain drugs. We report a case of acute coproporphyria induced by methandrostenolone. This is the first report of acute porphyria induced by an androgenic, anabolic steroid.

  9. The Use and Abuse of Anabolic Steroids: A Discussion for Health and Physical Education Teachers

    ERIC Educational Resources Information Center

    Thomas, John A.; And Others

    1973-01-01

    This article reviews research on anabolic steroids, indicating that athletes are mistaken in believing that taking them will improve their physical performance. Dangerous side-effects are also discussed. (JA)

  10. Female hormones: do they influence muscle and tendon protein metabolism?

    PubMed

    Hansen, Mette

    2017-08-29

    Due to increased longevity, women can expect to live more than one-third of their lives in a post-menopausal state, which is characterised by low circulating levels of oestrogen and progesterone. The aim of this review is to provide insights into current knowledge of the effect of female hormones (or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality and is associated with substantial financial costs. Resistance training and dietary optimisation can counteract or at least decelerate the degenerative ageing process, but lack of oestrogen in post-menopausal women may reduce their sensitivity to these anabolic stimuli and accelerate muscle loss. Tendons and ligaments are also affected by sex hormones, but the effect seems to differ between endogenous and exogenous female hormones. Furthermore, the effect seems to depend on the age, and as a result influence the biomechanical properties of the ligaments and tendons differentially. Based on the present knowledge oestrogen seems to play a significant role with regard to skeletal muscle protein turnover. Therefore, oestrogen/hormonal replacement therapy may counteract the degenerative changes in skeletal muscle. Nevertheless, there is a need for greater insight into the direct and indirect mechanistic effects of female hormones before any evidence-based recommendations regarding type, dose, duration and timing of hormone replacement therapy can be provided.

  11. Types of hormone therapy

    MedlinePlus

    ... types of hormone therapy; Hormone replacement therapy - types; Menopause - types of hormone therapy; HT - types; Menopausal hormone ... Menopause symptoms include: Hot flashes Night sweats Sleep problems Vaginal dryness Anxiety Moodiness Less interest in sex ...

  12. Optimization of Fibroblast Growth Factor-1 as an Anabolic Agent for Osteoporosis

    DTIC Science & Technology

    1997-10-01

    to develop fibroblast growth factor-1 through rational protein engineering into a potent and specific anabolic agent for the treatment of osteoporosis...program is to develop fibroblast growth factor-1 via protein engineering into a potent and specific anabolic agent for the treatment of osteoporosis and...years. It is probable that all people with the disease will ultimately benefit from treatments to increase bone formation. A more acute and relevant

  13. Optimization of Fibroblast Growth Factor-1 as an Anabolic Agent for Osteoporosis

    DTIC Science & Technology

    2001-10-01

    engineering into a potent and specific anabolic agent for the treatment of osteoporosis and fracture repair. The specific aims of this research plan are: 1) To...been to develop FGF-1 through protein engineering into a potent and specific anabolic agent for the treatment of osteoporosis and fracture repair...that all people with the disease will benefit from treatments designed to increase bone mass. The greatest therapeutic challenge in the osteoporosis

  14. Cardiotoxic effects of cocaine and anabolic-androgenic steroids in the athlete.

    PubMed

    Welder, A A; Melchert, R B

    1993-04-01

    Cocaine and anabolic-androgenic steroid abuse have become major drug problems in the United States. Cocaine has been designated as "the drug of greatest national health concern" while as many as 1 million Americans have used or are currently using anabolic-androgenic steroids to promote athletic performance and/or improve physical appearance. Unfavorable cardiovascular events have been linked to both cocaine and anabolic-androgenic steroid abuse in healthy, physically active individuals. Deaths of several United States athletes in 1986 focused attention on the life-threatening cardiovascular consequences of cocaine abuse. Reports of myocardial injury with anabolic-androgenic steroid abuse are anecdotal. Nevertheless, case reports have illustrated the alarming cardiotoxic potential of these steroids in athletes. Anabolic-androgenic steroids were correlated to myocardial infarction in weight lifters and cardiomyopathy in a former professional football player. From the total emergency room episodes where cocaine was mentioned in 1990, approximately 66% of these episodes occurred in young individuals 18-29 years of age. Over 500,000 of the individuals currently taking anabolic-androgenic steroids for nonmedical purposes are high-school children. Because cocaine and anabolic-androgenic steroids are used improperly, more focus needs to be paid to the toxic mechanisms of their adverse effects. Therefore, the purpose of this review is to discuss mechanisms whereby exercise and/or exercise training may alter the cardiovascular responses to these drugs. Furthermore, we would like to illustrate that contrary to the popular belief, acute and chronic abuse of cocaine and anabolic-androgenic steroids have a negative impact on exercise performance.

  15. Prevalence of use of anabolic steroids by bodybuilders using three methods in a city of iran.

    PubMed

    Nakhaee, Mohammad Reza; Pakravan, Faezeh; Nakhaee, Nouzar

    2013-01-01

    The prevalence of substance use among bodybuilding athletes has been poorly studied in Iran. This study was conducted to examine the prevalence of drug use, especially anabolic steroids, among bodybuilding athletes. This cross-sectional study was conducted in the first half of 2013 among body building athletes referring to gyms located in Kerman, Iran. Five gyms were selected randomly and 380 athletes were invited to complete a self-administered anonymous questionnaire, consecutively. The questionnaire included two parts; baseline characteristics and substance related questions. The prevalence of anabolic steroids was estimated based on three methods; self-report, projective question, and crosswise model. We enrolled 298 male athletes in the final analysis. Mean ± SD age of subjects was 25.9 ± 8.4. The most frequent recent (past 30 days) drug use was waterpipe smoking (45%). The second most frequently used drug was alcohol (26.5%, recent use). Based on self-reports, the prevalence of lifetime anabolic steroid use was calculated to be 24.5%. The corresponding figure based on crosswise method was obtained to be 56.8%. Participants believed that a median of 40% of athletes had used anabolic steroids in their lifetime. The prevalence of anabolic steroid was higher in single and less educated individuals (P < 0.05). The main reason for using anabolic steroids was to increase muscle size. The prevalence of drug use, especially tobacco, alcohol, and anabolic steroids, was high among bodybuilding athletes. We could not rely on self-reports to examine anabolic steroid use.

  16. Prevalence of Use of Anabolic Steroids by Bodybuilders Using Three Methods in a City of Iran

    PubMed Central

    Nakhaee, Mohammad Reza; Pakravan, Faezeh; Nakhaee, Nouzar

    2013-01-01

    Background The prevalence of substance use among bodybuilding athletes has been poorly studied in Iran. This study was conducted to examine the prevalence of drug use, especially anabolic steroids, among bodybuilding athletes. Methods This cross-sectional study was conducted in the first half of 2013 among body building athletes referring to gyms located in Kerman, Iran. Five gyms were selected randomly and 380 athletes were invited to complete a self-administered anonymous questionnaire, consecutively. The questionnaire included two parts; baseline characteristics and substance related questions. The prevalence of anabolic steroids was estimated based on three methods; self-report, projective question, and crosswise model. Findings We enrolled 298 male athletes in the final analysis. Mean ± SD age of subjects was 25.9 ± 8.4. The most frequent recent (past 30 days) drug use was waterpipe smoking (45%). The second most frequently used drug was alcohol (26.5%, recent use). Based on self-reports, the prevalence of lifetime anabolic steroid use was calculated to be 24.5%. The corresponding figure based on crosswise method was obtained to be 56.8%. Participants believed that a median of 40% of athletes had used anabolic steroids in their lifetime. The prevalence of anabolic steroid was higher in single and less educated individuals (P < 0.05). The main reason for using anabolic steroids was to increase muscle size. Conclusion The prevalence of drug use, especially tobacco, alcohol, and anabolic steroids, was high among bodybuilding athletes. We could not rely on self-reports to examine anabolic steroid use. PMID:24494162

  17. Compulsive weight lifting and anabolic drug abuse among women rape victims.

    PubMed

    Gruber, A J; Pope, H G

    1999-01-01

    In the course of a study of 75 female weight lifters, we encountered 10 (13%) who reported that they were raped as teenagers or adults. Nine of these women began or greatly increased their weight lifting activities after the assault to be better able to defend themselves against men. Seven began abusing anabolic steroids and/or clenbuterol to gain muscle mass. Compulsive weight lifting and anabolic substance abuse may represent another form of response to the trauma of sexual assault.

  18. [Possibilities in the use of anabolic substances as veterinary drugs for metaphylaxis and biotechnology].

    PubMed

    Lange, W; Padućeva, A L; Schuffenhauer, W; Klinsky, J D

    1977-01-01

    An account is given of the latest developments and trends in using anabolic preparations in animal husbandry. The development of veterinary medicaments for metaphylaxis and biological engineering in industrialised animal husbandry is explained and substantiated, with reference being made to protein-anabolic and growth-stimulating properties. However, full observation of and compliance with codes and bylaws on drug and food production will depend strongly on efficient interdisciplinary socialist teamworks.

  19. Development and validation of an enzyme-linked immunosorbent assay for the detection of circulating antibodies raised against growth hormone as a consequence of rbST treatment in cows.

    PubMed

    Rochereau-Roulet, Sandrine; Gaudin, Isabelle; Chéreau, Sylvain; Prévost, Stéphanie; André-Fontaine, Geneviève; Pinel, Gaud; Le Bizec, Bruno

    2011-08-26

    The recombinant bovine growth hormone (rbST) is used to increase lactating performances of dairy cows. Administration of rbST is banned in the European Union; nevertheless, its use is probable. Until now, efficient analytical strategies to detect such practice are based on the direct detection by mass spectrometry of the presence of rbST in biological fluids, which suits for confirmatory purposes. Current screening strategies do not offer satisfactory performances; therefore, alternative screening strategies are required. The aim of the present work is to develop and validate an ELISA to measure the production of specific antibodies upon rbST in bovine sera. In this immunoassay, rbST is absorbed onto microtiter plate. After specific purification of the antibodies in serum, samples are analysed and the presence of antibodies anti-rbST is detected by Protein G peroxidase conjugate and 2-2'-azino di-ethyl benz-thiazoline-6-sulphonic acid (ABTS). The mean reproducibility of the OD (λ=405 nm) measurement was calculated with a CV of 13%. The intra- and inter-assay CVs ranged from 0.79% to 7.91% and from 2.69% to 20% respectively. The test presents cross-reaction with other growth hormones such as the recombinant equine (reST) and porcine (pST) (100% and 80% respectively). The specificity of the test toward rbST anabolic treatment was confirmed through the analysis of sera samples collected on animals administered with other anabolic compounds (steroids). The performances of the present anti-rbST ELISA proves its efficiency as a new screening tool to highlight illegal administration of rbST in cattle up to at least 3 weeks after treatment.

  20. Immunologic Intervention in HIV Infection: Anti-Polymerase Responses and Hormonal Regulation

    DTIC Science & Technology

    1993-09-01

    cluster of Pneumocystis carinii pneumonia in adults without predisposing illnesses. N. Engl. J. Med. 324:246- 250. 20. Laurence J, Siegal FP, Schattner E... first model for investigation of control of HIV infection in B cells. This work also has implications for the pathogenesis of B cell lymphomas in AIDS...together with its anabolic properties, is of great interest in HIV disease. We have discovered that not only is growth hormone a potent T cell stimulant

  1. Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate.

    PubMed

    Thaler, Roman; Maurizi, Antonio; Roschger, Paul; Sturmlechner, Ines; Khani, Farzaneh; Spitzer, Silvia; Rumpler, Monika; Zwerina, Jochen; Karlic, Heidrun; Dudakovic, Amel; Klaushofer, Klaus; Teti, Anna; Rucci, Nadia; Varga, Franz; van Wijnen, Andre J

    2016-03-25

    Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2,Col1a1,Bglap2,Sp7,Atf4, andAlpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of theTet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorptionin vivo Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Neurotoxic properties of the anabolic androgenic steroids nandrolone and methandrostenolone in primary neuronal cultures.

    PubMed

    Caraci, Filippo; Pistarà, V; Corsaro, A; Tomasello, Flora; Giuffrida, Maria Laura; Sortino, Maria Angela; Nicoletti, Ferdinando; Copani, Agata

    2011-04-01

    Anabolic-androgenic steroid (AAS) abuse is associated with multiple neurobehavioral disturbances. The sites of action and the neurobiological sequels of AAS abuse are unclear at present. We investigated whether two different AASs, nandrolone and methandrostenolone, could affect neuronal survival in culture. The endogenous androgenic steroid testosterone was used for comparison. Both testosterone and nandrolone were neurotoxic at micromolar concentrations, and their effects were prevented by blockade of androgen receptors (ARs) with flutamide. Neuronal toxicity developed only over a 48-hr exposure to the steroids. The cell-impermeable analogues testosterone-BSA and nandrolone-BSA, which preferentially target membrane-associated ARs, were also neurotoxic in a time-dependent and flutamide-sensitive manner. Testosterone-BSA and nandrolone-BSA were more potent than their parent compounds, suggesting that membrane-associated ARs were the relevant sites for the neurotoxic actions of the steroids. Unlike testosterone and nandrolone, toxicity by methandrostenolone and methandrostenolone-BSA was insensitive to flutamide, but it was prevented by the glucocorticoid receptor (GR) antagonist RU-486. Methandrostenolone-BSA was more potent than the parent compound, suggesting that its toxicity relied on the preferential activation of putative membrane-associated GRs. Consistently with the evidence that membrane-associated GRs can mediate rapid effects, a brief challenge with methandrostenolone-BSA was able to promote neuronal toxicity. Activation of putative membrane steroid receptors by nontoxic (nanomolar) concentrations of either nandrolone-BSA or methandrostenolone-BSA became sufficient to increase neuronal susceptibility to the apoptotic stimulus provided by β-amyloid (the main culprit of AD). We speculate that AAS abuse might facilitate the onset or progression of neurodegenerative diseases not usually linked to drug abuse.

  3. Prevention of breast cancer skeletal metastases with parathyroid hormone

    PubMed Central

    Swami, Srilatha; Johnson, Joshua; Bettinson, Lance A.; Kimura, Takaharu; Zhu, Hui; Albertelli, Megan A.; Johnson, Rachelle W.; Wu, Joy Y.

    2017-01-01

    Advanced breast cancer is frequently associated with skeletal metastases and accelerated bone loss. Recombinant parathyroid hormone [teriparatide, PTH(1-34)] is the first anabolic agent approved in the US for treatment of osteoporosis. While signaling through the PTH receptor in the osteoblast lineage regulates bone marrow hematopoietic niches, the effects of anabolic PTH on the skeletal metastatic niche are unknown. Here, we demonstrate, using orthotopic and intratibial models of 4T1 murine and MDA-MB-231 human breast cancer tumors, that anabolic PTH decreases both tumor engraftment and the incidence of spontaneous skeletal metastasis in mice. Microcomputed tomography and histomorphometric analyses revealed that PTH increases bone volume and reduces tumor engraftment and volume. Transwell migration assays with murine and human breast cancer cells revealed that PTH alters the gene expression profile of the metastatic niche, in particular VCAM-1, to inhibit recruitment of cancer cells. While PTH did not affect growth or migration of the primary tumor, it elicited several changes in the tumor gene expression profile resulting in a less metastatic phenotype. In conclusion, PTH treatment in mice alters the bone microenvironment, resulting in decreased cancer cell engraftment, reduced incidence of metastases, preservation of bone microarchitecture and prolonged survival. PMID:28878134

  4. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells

    PubMed Central

    Basile, John R.; Binmadi, Nada O.; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks. PMID:23675320

  5. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells.

    PubMed

    Basile, John R; Binmadi, Nada O; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  6. Anabolic androgenic steroids reverse the beneficial effect of exercise on tendon biomechanics: an experimental study.

    PubMed

    Tsitsilonis, Serafim; Chatzistergos, Panayiotis E; Panayiotis, Chatzistergos E; Mitousoudis, Athanasios S; Athanasios, Mitousoudis S; Kourkoulis, Stavros K; Stavros, Kourkoulis K; Vlachos, Ioannis S; Ioannis, Vlachos S; Agrogiannis, George; George, Agrogiannis; Fasseas, Konstantinos; Konstantinos, Fasseas; Perrea, Despina N; Despina, Perrea N; Zoubos, Aristides B; Aristides, Zoubos B

    2014-06-01

    The effect of anabolic androgenic steroids on tendons has not yet been fully elucidated. Aim of the present study was the evaluation of the impact of anabolic androgenic steroids on the biomechanical and histological characteristics of Achilles tendons. Twenty-four male Wistar rats were randomized into four groups with exercise and anabolic steroids (nandrolone decanoate) serving as variables. Protocol duration was 12 weeks. Following euthanasia, tendons' biomechanical properties were tested with the use of a modified clamping configuration. Histological examination with light and electron microscopy were also performed. In the group of anabolic steroids and exercise the lowest fracture stress values were observed, while in the exercise group the highest ones. Histological examination by light and electron microscopy revealed areas of collagen dysplasia and an increased epitendon in the groups receiving anabolic steroids and exercise. These findings suggest that anabolic androgenic steroids reverse the beneficial effect of exercise, thus resulting in inferior maximal stress values. Copyright © 2013 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  7. Insulin is protein-anabolic in chronic renal failure patients.

    PubMed

    Lim, Victoria S; Yarasheski, Kevin E; Crowley, Jan R; Fangman, Jerry; Flanigan, Michael

    2003-09-01

    To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values ( micro mol/kg/h, mean +/- SEM) are presented in the sequence of B-HD, HD, and N, and only P < 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 +/- 7, 126 +/- 4, and 116 +/- 6, respectively. C (leucine oxidation rates) were 18 +/- 2, 17 +/- 2, and 21 +/- 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 +/- 6, 107 +/- 4, and 94 +/- 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were -18 +/- 2, -17 +/- 2, and -21 +/- 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 +/- 3, 98 +/- 6, and 94 +/- 5, respectively; C were 12 +/- 1, 11 +/- 2, and 18 +/- 1, respectively (P = 0.02); S were 77 +/- 4, 87 +/- 5, and 76 +/- 5, respectively, and balances were -12 +/- 1, -11 +/- 2, and -18 +/- 1, respectively (P = 0.02). During Flux 3 (high-dose insulin infusion): D were 77 +/- 3, 82 +/- 7, and 84 +/- 5, respectively; C were 9 +/- 1, 8 +/- 1, and 14 +/- 1, respectively (P = 0.005); S were 68 +/- 4, 74 +/- 6, and 70 +/- 5, respectively, and balances were -9 +/- 1, -8 +/- 1, and -14 +/- 1, respectively (P = 0.005). In Flux 4 (insulin infused with amino acids): D were 73 +/- 3, 107 +/- 18, and 85 +/- 7, respectively; C were 35 +/- 4, 29 +/- 5, and 39 +/- 3, respectively; S were 105 +/- 5, 145 +/- 15, and 113 +/- 6, respectively (P = 0.02), and balances were 32 +/- 4, 38 +/- 5, and 27 +/- 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone

  8. Androgenic anabolic steroid abuse and the cardiovascular system.

    PubMed

    Vanberg, Paul; Atar, Dan

    2010-01-01

    Abuse of anabolic androgenic steroids (AAS) has been linked to a variety of different cardiovascular side effects. In case reports, acute myocardial infarction is the most common event presented, but other adverse cardiovascular effects such as left ventricular hypertrophy, reduced left ventricular function, arterial thrombosis, pulmonary embolism and several cases of sudden cardiac death have also been reported. However, to date there are no prospective, randomized, interventional studies on the long-term cardiovascular effects of abuse of AAS. In this review we have studied the relevant literature regarding several risk factors for cardiovascular disease where the effects of AAS have been scrutinized:(1) Echocardiographic studies show that supraphysiologic doses of AAS lead to both morphologic and functional changes of the heart. These include a tendency to produce myocardial hypertrophy (Fig. 3), a possible increase of heart chamber diameters, unequivocal alterations of diastolic function and ventricular relaxation, and most likely a subclinically compromised left ventricular contractile function. (2) AAS induce a mild, but transient increase of blood pressure. However, the clinical significance of this effect remains modest. (3) Furthermore, AAS confer an enhanced pro-thrombotic state, most prominently through an activation of platelet aggregability. The concomitant effects on the humoral coagulation cascade are more complex and include activation of both pro-coagulatory and fibrinolytic pathways. (4) Users of AAS often demonstrate unfavorable measurements of vascular reactivity involving endothelial-dependent or endothelial-independent vasodilatation. A degree of reversibility seems to be consistent, though. (5) There is a comprehensive body of evidence documenting that AAS induce various alterations of lipid metabolism. The most prominent changes are concomitant elevations of LDL and decreases of HDL, effects that increase the risk of coronary artery disease

  9. Parathyroid hormone and bone healing.

    PubMed

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-07-01

    Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cance