The concept of multiple hormonal dysregulation

PubMed Central

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

2016-01-01

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. (www.actabiomedica.it) PMID:20518188

[Determination of 11 anabolic hormones in fish tissue by multi-function impurity adsorption solid-phase extraction-ultrafast liquid chromatography-tandem mass spectrometry].

PubMed

Yao, Shanshan; Zhao, Yonggang; Li, Xiaoping; Chen, Xiaohong; Jin, Micong

2012-06-01

A method was developed for the determination of 11 anabolic hormones (boldenone, androstenedione, nandrolone, methandrostenolone, methyltestosterone, testosterone, testosterone acetate, trenbolone, testosterone propionate, stanozolol, fluoxymesterone) in fish by multi-function impurity adsorption solid-phase extraction-ultrafast liquid chromatography-tandem mass spectrometry. After the sample was extracted by methanol, the extract was cleaned-up quickly by C18 adsorbent, neutral alumina adsorbent and amino-functionalized nano-adsorbent. The separation was performed on a Shim-Pack XR-ODS II column (100 mm x 2.0 mm, 2.2 microm) using the mobile phases of 0.1% (v/v) formic acid in acetonitrile and 0.1% (v/v) formic acid solution in a gradient elution mode. The identification and quantification were achieved by using electrospray ionization in positive ion mode (ESI+) in multiple reaction monitoring (MRM) mode. The matrix-matched external standard calibration curves were used for quantitative determination. The results showed that the calibration curves were in good linearity for the eleven analytes with the correlation coefficients (r) more than 0.999. The limits of detection (LODs, S/N > 3) for the 11 anabolic hormones were from 0.03 microg/kg to 0.4 microg/kg and the limits of quantification (LOQs, S/N > 10) were from 0.1 microg/kg to 1.5 microg/kg. The average recoveries ranged from 80.9% to 98.1% with the relative standard deviations between 5.2% and 11.5%. The method is simple, rapid, sensitive, accurate and suitable for the quantitative determination and confirmation of the 11 anabolic hormones in fish.

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.

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.

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

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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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…

The neurobiology and addiction potential of anabolic androgenic steroids and the effects of growth hormone.

PubMed

Grönbladh, Alfhild; Nylander, Erik; Hallberg, Mathias

2016-09-01

Anabolic androgenic steroids (AAS) are substances that mimic the hormone testosterone, and primarily act via the androgen receptor. In addition to their physiological effect on muscle tissue and growth, research from the last decade has shown that AAS have a pronounced impact on the central nervous system. A large number of studies have demonstrated that AAS affect the mesolimbic reward system in the brain. However, whether the direct effects of AAS on endorphins, dopamine, serotonin and GABA etc. and on the corresponding and related systems lead to dependence needs to be further elucidated. According to recent studies, the prevalence of AAS dependence among AAS users has been estimated to be approximately 30%, and polysubstance use, of both pharmaceutical drugs and narcotics, within this group is common. The present review primarily discusses AAS in the context of addiction and dependence, and further addresses the issue of using multiple substances, i.e. stimulants and opiates in combination with AAS. In addition, aspects of the treatment of AAS dependence, the connection between AAS abuse and cognition, and AAS-induced neurotoxicity are presented. Currently, performance enhancing drugs are frequently used in combination with AAS. Therefore, a large section on growth hormone and insulin-like growth factor is also included. Copyright © 2016. Published by Elsevier Inc.

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

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.

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.

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

Cardiometabolic Risks During Anabolic Hormone Supplementation in Older Men

PubMed Central

He, J.; Bhasin, S; Binder, E.F.; Yarasheski, K.E.; Castaneda-Sceppa, C.; Schroeder, E.T.; Roubenoff, R.; Chou, C-P.; Azen, S.P.; Sattler, F.R.

2012-01-01

There is little prospective information on the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging. We conducted a double-masked, partially placebo controlled study in 112 men 65–90 years-old. Transdermal testosterone (5g-vs-10g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0-vs-3-vs-5ug/kg/day) were administered for 16-weeks. Measurements included testosterone and IGF-1 levels, body composition by DEXA, and cardiometabolic risk factors (upper body fat, blood pressure, insulin sensitivity, fasting triglycerides, HDL-cholesterol, and serum adiponectin) at baseline and after 16 weeks of treatment. Some cardiometabolic factors improved (total and trunk fat, triglycerides, HDL-cholesterol) and others worsened (systolic blood pressure, insulin sensitivity index [QUICKI], adiponectin). Cardiometabolic risk composite scores (CRCS) improved (−0.69±1.55, p<0.001). In multivariate analyses, QUICKI, triglycerides, and HDL-cholesterol contributed 33%, 16%, and 14% of the variance in CRCS, respectively. Pathway analyses indicated that changes in fat and lean mass were related to individual cardiometabolic variables and CRCS in a complex manner. Changes in BMI, reflecting composite effects of changes in fat and lean mass, were more robustly associated with cardiometabolic risks than changes in fat mass or LBM individually. In conclusion, testosterone and rhGH administration was associated with diverse changes in individual cardiometabolic risk factors, but in aggregate appeared not to worsen cardiometabolic risk in healthy older men after 4-months. The long term effects of these and similar anabolic therapies on cardiovascular events should be investigated in populations with greater funtional limitations along with important health disabilities including upper body obesity and other cardiometabolic risks. PMID:23784898

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…

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…

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.

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

2017-10-01

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.

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.

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.

[Dangers and risks of black market anabolic steroid abuse in sports --gas chromatography-mass spectrometry analyses].

PubMed

Ritsch, M; Musshoff, F

2000-03-01

Anabolic steroids have become increasingly popular among athletes even at subcompetitive or recreational level instead of extensive doping tests, educational campaigns and lethal incidents. Nowadays, the fitness boom has also produced a population of steroid users at high school level and also under non-sports practicing children. After opening the borders to East Europe an explosion of the black-market for anabolic steroids occurred. Beside the well-known side effects of anabolic steroids new problems and risks occurred due to fake drugs from the black market. This review ist subdivided into two parts: We provide a detailed review of the literature an anabolic steroids to the reader the information needed to make an informed decision an the relative risks and benefits of anabolic steroids. Secondly, we evaluated 40 "anabolic steroids" obtained from the black market using mass spectrometry or gas chromatography analysis to evaluate the real pharmacological compounds. As the results of this analysis, we found that 15 (37.5%) these drugs contained different or any pharmacological compounds as labeled. From the external packing, a differentiation between original and the fake drugs was impossible. Therefore, a large information and credibility gap concerning anabolic steroids particular those from the black market exists between the athletes and the medical and scientific communities. We believe that this gap can only be closed if both groups are be better informed about anabolic steroids.

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

PubMed

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

Hormonal responses to resistance exercise during different menstrual cycle states.

PubMed

Nakamura, Yuki; Aizawa, Katsuji; Imai, Tomoko; Kono, Ichiro; Mesaki, Noboru

2011-06-01

To investigate the effect of menstrual cycle states on ovarian and anabolic hormonal responses to acute resistance exercise in young women. Eight healthy women (eumenorrhea; EM) and eight women with menstrual disorders including oligomenorrhea and amenorrhea (OAM) participated in this study. The EM group performed acute resistance exercises during the early follicular (EF) and midluteal (ML) phases, and the OAM group performed the same exercises. All subjects performed three sets each of lat pull-downs, leg curls, bench presses, leg extensions, and squats at 75%-80% of one-repetition maximum with a 1-min rest between sets. Blood samples were obtained before exercise, immediately after, 30 min after, and 60 min after the exercise. In the EM group, resting serum levels of estradiol and progesterone in the ML phase were higher than those in the EF phase and higher than those in the OAM group. Serum estradiol and progesterone in the ML phase increased after the exercise but did not change in the EF phase or in the OAM group. In contrast, resting levels of testosterone in the OAM group were higher than those in both the ML and EF phases of the EM group. After the exercise, serum growth hormone increased in both the ML and EF phases but did not change in the OAM group. The responses of anabolic hormones to acute resistance exercise are different among the menstrual cycle states in young women. Women with menstrual disturbances with low estradiol and progesterone serum levels have an attenuated anabolic hormone response to acute resistance exercise, suggesting that menstrual disorders accompanying low ovarian hormone levels may affect exercise-induced change in anabolic hormones in women.

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

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 (EC 50 ) 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.

Psychological treatment of anabolic-androgenic steroid-dependent individuals.

PubMed

Corcoran, J P; Longo, E D

1992-01-01

Anabolic-androgenic steroids (AAS) are synthetic derivatives of the sex hormone testosterone. Anabolic refers to the "growth-promoting" effect while androgenic refers to the "masculinizing" effect. It is becoming more evident that nonathletes as well as athletes are abusing AAS. Although the abuse of alcohol and other drugs contribute significantly to current chemical use problems in American society, AAS abuse is one of the fastest growing "new drug" problems facing secondary and higher education institutes of learning. The purpose of this discussion is to present working hypotheses regarding the psychological treatment of AAS dependent individuals. The treatment approach presented incorporates the approaches used with eating disorders, substance abuse/dependence, and narcissistic personality disorders. This paper considers some of the preliminary considerations for the first phase of treatment, some pitfalls to avoid, and therapist characteristics, as well as treatment modalities that might be helpful in the treatment of AAS-dependent individuals.

Anabolic Therapy for the Treatment of Osteoporosis in Childhood.

PubMed

Ward, Leanne M; Rauch, Frank

2018-06-01

Numerous forms of osteoporosis in childhood are characterized by low bone turnover (for example, osteoporosis due to neuromuscular disorders and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to treat osteoporosis in the young, is associated with further reductions in bone turnover, raising concerns about the long-term safety and efficacy of such therapy. These observations have led to increasing interest in the role of anabolic therapy to treat pediatric osteoporosis. While growth hormone and androgens appears to be relatively weak anabolic modulators of bone mass, emerging therapies targeting bone formation pathways (anti-transforming growth factor beta antibody and anti-sclerostin antibody) hold considerable promise. Teriparatide remains an attractive option that merits formal study for patients post-epiphyseal fusion, although it must be considered that adult studies have shown its effect is blunted when administered following bisphosphonate therapy. Mechanical stimulation of bone through whole body vibration therapy appears to be much less effective than bisphosphonate therapy for treating osteoporosis in children. New anabolic therapies which target important pathways in skeletal metabolism merit further study in children, including their effects on fracture risk reduction and after treatment discontinuation.

Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays.

PubMed

Houtman, Corine J; Sterk, Saskia S; van de Heijning, Monique P M; Brouwer, Abraham; Stephany, Rainer W; van der Burg, Bart; Sonneveld, Edwin

2009-04-01

Anabolic androgenic steroids (AAS) are a class of steroid hormones related to the male hormone testosterone. They are frequently detected as drugs in sport doping control. Being similar to or derived from natural male hormones, AAS share the activation of the androgen receptor (AR) as common mechanism of action. The mammalian androgen responsive reporter gene assay (AR CALUX bioassay), measuring compounds interacting with the AR can be used for the analysis of AAS without the necessity of knowing their chemical structure beforehand, whereas current chemical-analytical approaches may have difficulty in detecting compounds with unknown structures, such as designer steroids. This study demonstrated that AAS prohibited in sports and potential designer AAS can be detected with this AR reporter gene assay, but that also additional steroid activities of AAS could be found using additional mammalian bioassays for other types of steroid hormones. Mixtures of AAS were found to behave additively in the AR reporter gene assay showing that it is possible to use this method for complex mixtures as are found in doping control samples, including mixtures that are a result of multi drug use. To test if mammalian reporter gene assays could be used for the detection of AAS in urine samples, background steroidal activities were measured. AAS-spiked urine samples, mimicking doping positive samples, showed significantly higher androgenic activities than unspiked samples. GC-MS analysis of endogenous androgens and AR reporter gene assay analysis of urine samples showed how a combined chemical-analytical and bioassay approach can be used to identify samples containing AAS. The results indicate that the AR reporter gene assay, in addition to chemical-analytical methods, can be a valuable tool for the analysis of AAS for doping control purposes.

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…

[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.

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. Copyright © 2015 the American Physiological Society.

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

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.

Insulin-like growth factor-I, physical activity, and control of cellular anabolism.

PubMed

Nindl, Bradley C

2010-01-01

The underlying mechanisms responsible for mediating the beneficial outcomes of exercise undoubtedly are many, but the insulin-like growth factor-I (IGF-I) system is emerging as an important and central hormonal axis that plays a significant role concerning cellular anabolism. This introductory article summarizes the intent and the content for papers presented as part of a 2008 American College of Sports Medicine national symposium entitled "Insulin-like Growth Factor-I, Physical Activity, and Control of Cellular Anabolism." The individual authors and their papers are as follows: Jan Frystyk authoring "The relationship between exercise and the growth hormone/insulin-like growth factor-I axis," Greg Adams authoring "IGF-I signaling in skeletal muscle and the potential for cytokine interactions," and Brad Nindl authoring "Insulin-like growth factor-I as a biomarker of health, fitness, and training status." These papers focus on 1) different assay methodologies for IGF-I within the paradigm of exercise studies, 2) research demonstrating that intracellular signaling components associated with several proinflammatory cytokines have the potential to interact with anabolic signaling processes in skeletal muscle, and 3) an overview of IGF-I as a biomarker related to exercise training, muscle and bone remodeling, body composition, cognition, and cancer. When summed in total, the contribution that these papers will make will undoubtedly involve bringing attention to the vast regulatory complexity of the IGF-I system and will hopefully convince the reader that the IGF-I system warrants further detailed scientific inquiry to resolve many unanswered questions and paradoxical experimental findings. The IGF-I system remains one of the most intriguing and captivating marvels of human physiology that seems central in mediating numerous adaptations from physical activity.

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.

New anabolic therapies in osteoporosis.

PubMed

Rubin, Mishaela R; Bilezikian, John P

2003-03-01

Anabolic agents represent an important new advance in the therapy of osteoporosis. Their potential might be substantially greater than the anti-resorptives. Because the anti-resorptives and anabolic agents work by completely distinct mechanisms of action, it is possible that the combination of agents could be significantly more potent than either agent alone. Recent evidence suggests that a plateau in BMD might occur after prolonged exposure to PTH. Anti-resorptive therapy during or after anabolic therapy might prevent this skeletal adaptation. Protocols to consider anabolic agents as intermittent recycling therapy would be of interest. Of all the anabolics, PTH is the most promising. However, there are unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. More large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Rising expectations that anabolic therapies for osteoporosis will soon play a major role in treating this disease are likely to fuel further studies and the development of even more novel approaches to therapy.

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

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

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.

[Compounds modulating parathyroid hormone (PTH) secretion].

PubMed

Nagano, N; Iijima, H

2001-08-01

The control of parathyroid hormone (PTH) secretion is strictly regulated by the parathyroid Ca receptor (CaR). Calcimimetics and calcilytics selectively act on the parathyroid CaR to inhibit and enhance PTH secretion, respectively. According to the recent pharmacological two-state model, calcimimetics act on the CaR as allosteric agonists to stabilize an active conformation of CaR. Conversely, calcilytics act on the CaR as allosteric inverse agonists to stabilize an inactive conformation of CaR. These compounds that can alter circulating levels of PTH and bone turnover might provide novel treatments for adynamic bone disease in patients with chronic renal failure.

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.

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.

Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia.

PubMed

Ishii, H; Wada, M; Furuya, Y; Nagano, N; Nemeth, E F; Fox, J

2000-02-01

The calcium receptor agonist (calcimimetic) compound NPS R-568 causes rapid decreases in circulating levels of parathyroid hormone (PTH) in rats and humans. We hypothesized that daily intermittent decreases in serum PTH levels may have different effects on bone than do chronically sustained decreases. To test this hypothesis, we compared two NPS R-568 dosing regimens in rats with chronic renal insufficiency induced by two intravenous injections of adriamycin. Fourteen weeks after the second adriamycin injection, creatinine clearance was reduced by 52%, PTH levels were elevated approximately 2.5-fold, and serum 25(OH)D3 and 1,25(OH)2D3 levels were reduced substantially. Treatment by daily per os gavage, which decreased PTH levels intermittently, or continuous subcutaneous infusion, which resulted in a sustained suppression of serum PTH levels, then began for 8 weeks. Despite the hyperparathyroidism, the adriamycin-injected rats developed a low-turnover bone lesion with osteomalacia (fourfold increase in osteoid volume in the proximal tibial metaphysis) and osteopenia (67% decrease in cancellous bone volume and an 18% reduction in bone mineral density at the distal femur). Daily administered (but not infused) NPS R-568 significantly increased cancellous bone volume solely by normalizing trabecular thickness, and increased femoral bone mineral density by 14%. These results indicate that daily intermittent, but not sustained, decreases in PTH levels have an "anabolic-like" effect on bones with a low-turnover lesion in this animal model of chronic renal insufficiency.

[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.

Anabolic effect of Hibiscus rosasinensis Linn. leaf extracts in immature albino male rats.

PubMed

Olagbende-Dada, S O; Ezeobika, E N; Duru, F I

2007-01-01

Many plants remedies have been employed in solving man's health needs especially the nutritive value which enhances health living. Aphrodisiac plants are plants with anabolic properties i.e. they help in protein synthesis and enhances sexual abilities in males. They are also known as androgenic plants because their properties are similar to that of androgen a male hormone. Cold aqueous extract of Hibiscus rosasinensis leaves is reported by local traditional practioners in Western Nigeria to be aphrodisiac. To investigate the anabolic properties of Hibiscus rosasinensis. Three groups (8/group) of immature male rats of known weights were administered equal doses of aqueous (cold and hot) and alcoholic extracts of Hibiscus rosasinensis leaves for 8 weeks. The gain in body and isolated sexual organs (testis, epididymis, seminal vesicle and prostate) weights were determined after treatment and compared to the value obtained from a fourth untreated group which served as the control. Section through the testes of both the treated and untreated rats were also examined microscopically and displayed as a photomicrograph for comparism. All data were statistically analysed and displaced in graphic form. Over the 8 weeks of treatment, the control, the cold aqueous extract dosed, hot aqueous extract dosed and alcoholic extract dosed rats gained 8%, 15%, 18% and 22% in body weights respectively. The increase in the weight of testis, epididymis, seminal vesicle and prostate of the alcoholic extract dosed rats was 19%, 30%, 31% and 40% respectively. The anabolic effect of the leaf extracts of H. rosasinensis is hereby established. More work needs to be done on these leaf extracts to know their effect on the gonadotrophin hormones which regulate the activity of the androgens in relation to spermatogenesis.

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.

History and epidemiology of anabolic androgens in athletes and non-athletes.

PubMed

Kanayama, Gen; Pope, Harrison G

2018-03-15

The use of androgens, frequently referred to as anabolic-androgenic steroids (AAS), has grown into a worldwide substance abuse problem over the last several decades. Testosterone was isolated in the 1930s, and numerous synthetic androgens were quickly developed thereafter. Athletes soon discovered the dramatic anabolic effects of these hormones, and AAS spread rapidly through elite athletics and bodybuilding from the 1950s through the 1970s. However it was not until the 1980s that widespread AAS use emerged from the elite athletic world and into the general population. Today, the great majority of AAS users are not competitive athletes, but instead are typically young to middle-aged men who use these drugs primarily for personal appearance. AAS abuse has now become particularly prevalent in regions such as Scandinavia, the United States, Brazil, and British Commonwealth countries, but remains rare in countries such as China, Korea, and Japan - a pattern that reflects cultural differences in attitudes towards male muscularity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Pharmacodynamics of selective androgen receptor modulators.

PubMed

Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

2003-03-01

The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

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.

Muscle wasting and resistance of muscle anabolism: the "anabolic threshold concept" for adapted nutritional strategies during sarcopenia.

PubMed

Dardevet, Dominique; Rémond, Didier; Peyron, Marie-Agnès; Papet, Isabelle; Savary-Auzeloux, Isabelle; Mosoni, Laurent

2012-01-01

Skeletal muscle loss is observed in several physiopathological situations. Strategies to prevent, slow down, or increase recovery of muscle have already been tested. Besides exercise, nutrition, and more particularly protein nutrition based on increased amino acid, leucine or the quality of protein intake has generated positive acute postprandial effect on muscle protein anabolism. However, on the long term, these nutritional strategies have often failed in improving muscle mass even if given for long periods of time in both humans and rodent models. Muscle mass loss situations have been often correlated to a resistance of muscle protein anabolism to food intake which may be explained by an increase of the anabolic threshold toward the stimulatory effect of amino acids. In this paper, we will emphasize how this anabolic resistance may affect the intensity and the duration of the muscle anabolic response at the postprandial state and how it may explain the negative results obtained on the long term in the prevention of muscle mass. Sarcopenia, the muscle mass loss observed during aging, has been chosen to illustrate this concept but it may be kept in mind that it could be extended to any other catabolic states or recovery situations.

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

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.

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.

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.

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 expressly...

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 expressly...

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 expressly...

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 expressly...

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 expressly...

Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study.

PubMed

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

2010-02-01

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. In a representative sample of 716 men and women aged >or=65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha 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. 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. 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.

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

Growth hormone-insulin-like growth factor-1 and inflammatory response to a single exercise bout in children and adolescents.

PubMed

Nemet, Dan; Eliakim, Alon

2010-01-01

Physical activity plays an important role in tissue anabolism, growth and development, but the mechanisms that link patterns of exercise with tissue anabolism are not completely understood. The effectiveness of physical training depends on the training load and on the individual ability to tolerate it, and an imbalance between the two may lead to under or over-training. Therefore, many efforts have been made to find objective parameters to quantify the balance between training load and the athlete's tolerance. One of the unique features of exercise is that it leads to a simultaneous increase of antagonistic mediators. On the one hand, exercise stimulates anabolic components of the growth hormone (GH) → IGF-1 (insulin-like growth factor-1) axis. On the other hand, exercise elevates catabolic pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α). This emphasizes probably the importance of optimal adaptation to exercise in particularly during adolescence. The very fine balance between the anabolic and inflammatory/catabolic response to exercise will determine the effectiveness of exercise training and the health consequences of exercise. If the anabolic response is stronger, exercise will probably lead ultimately to increased muscle mass and improved fitness. A greater catabolic response, in particularly if persists for long duration, may lead to overtraining. Therefore, changes in the anabolic-catabolic hormonal balance and in circulating inflammatory cytokines can be used by adolescent athletes and/or their coaches to gauge the training intensity in individual and team sports. Copyright © 2010 S. Karger AG, Basel.

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.

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

Effects of aging and insulin resistant states on protein anabolic responses in older adults.

PubMed

Morais, Jose A; Jacob, Kathryn Wright; Chevalier, Stéphanie

2018-07-15

Insulin is the principal postprandial anabolic hormone and resistance to its action could contribute to sarcopenia. We developed different types of hyperinsulinemic clamp protocols to measure simultaneously glucose and protein metabolism in insulin resistant states (older adults, obesity, diabetes, etc.). To define effects of healthy aging in response to insulin, we employed the hyperinsulinemic, euglycemic and isoaminoacidemic (HYPER-1) clamp. The net whole-body anabolic (protein balance) response to hyperinsulinemia was lower in the elderly vs young (p = 0.007) and was highly correlated with the clamp glucose rate of disposal (r = 0.671, p < 0.001), indicating insulin resistance of protein metabolism concurrent with that of glucose. Differences in insulin resistance due to aging were observed predominantly in men, with older ones exhibiting significant lower anabolism compared with young ones. As most of the anabolism occurs during feeding, we studied the fed-state metabolic responses with aging using the hyperinsulinemic, hyperglycemic and hyperaminoacidemic clamp, including muscle biopsies. Older women showed comparable whole-body protein anabolic responses and stimulation of mixed-muscle protein synthesis by feeding to the young. The responses of skeletal muscle insulin signaling through the Akt-mTORC1 pathway were also unaltered, and therefore consistent with muscle protein synthesis results. Given that type 2 diabetes infers insulin resistance of protein metabolism with aging, we studied 10 healthy, 8 obese, and 8 obese type 2 diabetic elderly women using the HYPER-1 clamp. When compared to the group of young lean women to define the effects of obesity and diabetes with aging, whole-body change in net protein balance with hyperinsulinemia was similarly blunted in obese and diabetic older women. However, only elderly obese women with diabetes had lower net balance than lean older women. We conclude that with usual aging, the blunted whole

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

Sex hormones and skeletal muscle weakness.

PubMed

Sipilä, Sarianna; Narici, Marco; Kjaer, Michael; Pöllänen, Eija; Atkinson, Ross A; Hansen, Mette; Kovanen, Vuokko

2013-06-01

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

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.

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

Anabolic steroid use among students at a British college of technology.

PubMed

Williamson, D J

1993-09-01

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.

Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.

PubMed

Vrahnas, Christina; Pearson, Thomas A; Brunt, Athena R; Forwood, Mark R; Bambery, Keith R; Tobin, Mark J; Martin, T John; Sims, Natalie A

2016-12-01

Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls. 8week old male C57BL/6 mice were treated with vehicle or 50μg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15μm 2 regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation. The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone. These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual. Copyright © 2016

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.

Physiological concentrations of anabolic steroids in human hair.

PubMed

Shen, Min; Xiang, Ping; Shen, Baohua; Bu, Jun; Wang, Mengye

2009-01-30

Doping with endogenous anabolic steroids is one of the most serious issues in sports today. The measurement of anabolic steroid levels in human hair is necessary in order to distinguish between pharmaceutical steroids and natural steroids. This is the first investigation into the physiological concentrations of anabolic steroids in human hair in Chinese subjects. A gas chromatography-tandem mass spectrometry (GC/MS/MS) method was developed for the simultaneous identification and quantitation of five endogenous anabolic steroids (testosterone, epitestosterone, androsterone, etiocholanolone and dehydroepiandrosterone) in hair. After basic hydrolysis, hair samples were extracted with diethyl ether, derivatized and then detected using GC/MS/MS in the multiple-reaction monitoring mode (MRM). The one precursor/two product ion transitions for each anabolic steroid were monitored. The limits of detection for the five endogenous anabolic steroids were in the 0.1-0.2 pg/mg range. All analytes showed good linearity and the extraction recoveries were 74.6-104.5%. Within-day and between-day precisions were less than 20%. This method was applied to the analysis of testosterone, epitestosterone, androsterone, etiocholanolone, and dehydroepiandrosterone in human hair. Full-length hair samples were taken at the skin surface from the vertex of 39 males, 30 females and 11 children from China. None of the subjects were professional athletes. Testosterone and dehydroepiandrosterone were detected in all the hair segments. The physiological concentrations of testosterone were in the range 0.8-24.2 pg/mg, 0.1-16.8 pg/mg and 0.2-11.5 pg/mg in males, females and children, respectively, however, the mean values of dehydroepiandrosterone were much higher than the concentrations of testosterone. These data are suitable reference values and are the basis for the interpretation of results from investigations into the abuse of endogenous anabolic steroids.

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

Drug Facts: Anabolic Steroids

MedlinePlus

Skip to main content En español Researchers Medical & Health Professionals Patients & ... Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine ...

Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

PubMed

Gooi, J H; Pompolo, S; Karsdal, M A; Kulkarni, N H; Kalajzic, I; McAhren, S H M; Han, B; Onyia, J E; Ho, P W M; Gillespie, M T; Walsh, N C; Chia, L Y; Quinn, J M W; Martin, T J; Sims, N A

2010-06-01

The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exemption of certain anabolic steroid products... SCHEDULES OF CONTROLLED SUBSTANCES Exempt Anabolic Steroid Products § 1308.33 Exemption of certain anabolic steroid products; application. (a) The Administrator, upon the recommendation of Secretary of Health and...

Glycolytic reliance promotes anabolism in photoreceptors

PubMed Central

Chinchore, Yashodhan; Begaj, Tedi; Wu, David; Drokhlyansky, Eugene; Cepko, Constance L

2017-01-01

Vertebrate photoreceptors are among the most metabolically active cells, exhibiting a high rate of ATP consumption. This is coupled with a high anabolic demand, necessitated by the diurnal turnover of a specialized membrane-rich organelle, the outer segment, which is the primary site of phototransduction. How photoreceptors balance their catabolic and anabolic demands is poorly understood. Here, we show that rod photoreceptors in mice rely on glycolysis for their outer segment biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the size of the outer segments. Fibroblast growth factor signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in outer segment maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type. DOI: http://dx.doi.org/10.7554/eLife.25946.001 PMID:28598329

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 ...

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.

Review of Androgenic Anabolic Steroid Use

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. Borges; G. Eisele; C. Byrd

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 ormore » 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).« less

Use of dietary supplements and hormones in adolescents: A cautionary tale

PubMed Central

Guyda, Harvey J

2005-01-01

Ergogenic aids, such as nutritional supplements, anabolic steroids and human growth hormone, are increasingly being used to enhance sports performance or body image. While few rigorous scientific studies have derived significant conclusions, the marketing and promotion of most supplements is intense and far exceeds the data supporting their use. Particular concern has arisen regarding safety in the use of these substances among adolescents, who may be at particular risk when using caffeine-ephedra and anabolic steroid combinations. Indeed, long-term effects and fatalities have been reported. As a consequence, the American Academy of Pediatrics has condemned the use of anabolic steroid use for bodybuilding or performance enhancement in adolescents. Health care professionals need to educate themselves about ergogenic use and ask informed questions of their adolescent patients. An honest discussion of the limitations of most supplements, and acknowledgement that some supplements may work some of the time, may allow the physician to be more credible and useful in providing medical care and guidance to the adolescent seeking to improve body image or athletic performance. PMID:19668667

Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone.

PubMed

Bouleftour, Wafa; Bouet, Guenaelle; Granito, Renata Neves; Thomas, Mireille; Linossier, Marie-Thérèse; Vanden-Bossche, Arnaud; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

2015-03-01

Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins. © 2014 Wiley Periodicals, Inc., A Wiley Company.

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.

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.

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

The Role of the Multiple Hormonal Dysregulation in the Onset of "Anemia of Aging": Focus on Testosterone, IGF-1, and Thyroid Hormones.

PubMed

Maggio, Marcello; De Vita, Francesca; Fisichella, Alberto; Lauretani, Fulvio; Ticinesi, Andrea; Ceresini, Graziano; Cappola, Anne; Ferrucci, Luigi; Ceda, Gian Paolo

2015-01-01

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is "unexplained." Ageing process is also characterized by a "multiple hormonal dysregulation" with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.

Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemic colon anastomosis in rats.

PubMed

Yarimkaya, Ali; Apaydin, Berat; Unal, Ethem; Karabicak, Ilhan; Aydogan, Fatih; Uslu, Ezel; Erginoz, Ethem; Artis, Tarik; Eyuboglu, Erhun

2003-12-01

Recombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the healing of ischemic colon anastomosis in rats. Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemic colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic healing. Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemic colonic anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonic anastomosis.

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

The use and abuse of anabolic steroids in Olympic-caliber athletes.

PubMed

Bergman, R; Leach, R E

1985-09-01

Self-medication with anabolic steroids by athletes, particularly in the sports of weight lifting and track and field, has become increasingly popular. In the 1983 Pan American Games, 15 athletes were disqualified for taking anabolic steroids. Athletes take steroids believing the steroids will allow increased periods of intensive training and will increase muscle strength with proper weight training. The athletes assume this increased strength and training will translate into better athletic performance. Most athletes taking anabolic steroids are taking very large doses with no thought as to the potential adverse side effects. They ignore the possibility of long-term problems relating to hypertension, liver dysfunction, and atherosclerosis for what they see as the immediate performance benefits. In an attempt to keep sports competition "clean" and to help protect athletes from harmful drugs, the International Olympic Committee (IOC) and the United States Olympic Committee have rules stating that the use of anabolic steroids is illegal. Drug testing is performed in Olympic and in many international competitions. Those people found using anabolic steroids are disqualified. This use of anabolic steroids indicates that for some athletes the need to win or to maximize performance supersedes any worries about future health.

The role of sex differences in the effect of anabolics on the liver.

PubMed

Kulcsár-Gergely, J; Kulcsár, A; Kiss, A

1975-03-01

The effect of two anabolic steroids, norandrostenolone-phenylpropionate (Nerobolil) and norandrostenolone-decanoate (Retabolil) on the liver was studied in rats. Body weight, wet liver weight and the protein content of the liver homogenisates were found to increase under the effect of anabolic treatment, the most explicitely in females treated with Nerobolil. The function of the liver to metabolize hexobarbital, measured in vivo, is increased by a single dose of anabolic. The prolongation of treatment keeps on shortening hexobarbital anaesthesia only in females. Even 8 weeks after the end of treatment the effect is invariably lasting in females, in males it is not. Studies of the vaginal cycle cannot prove a decline of ovarial function. In females the hepatotropic effect of anabolic treatment, performed simultaneously with the chronic carbon tetrachloride lesion can be demonstrated. The liver weight and protein content are maintained on the control level. Under the effect of anabolic treatment the function to metabolize the effect of anabolic treatment the function to metabolize hexobarbital, which has been impaired by the lesion, remains near the level of the untreated animals. Our experiments support the observations of the inductive property of the steroids being parallel to their anabolic characteristics. Their catatoxic effect is pronounced in females. Nerobolil was found to be more advantageous from the point of view of both anabolic and hepatotropic effect. Our experiments do not suggest the possibility of liver damage during the administration of these two anabolics. The effect of the anabolics on the enzymatic induction may be of therapeutic value when adequate preparations are selected and sex differences as well as the character of the liver damage are taken into consideration.

[Anabolic steroid induced hypogonadism in men: overview and case report].

PubMed

Stárka, Luboslav; Dušková, Michaela; Kolátorová, Lucie; Lapčík, Oldřich

An important potential consequence of the anabolic steroid misuse is hypogonadotropic hypogonadism due to the inhibition of pituitary secretion of gonadotropins. By the symptoms as testicular atrophy, spermatogenic and fertility disturbances or dysfunction in sexual life, the anabolic steroids induced hypogonadism (ASIH) could be differentiated from organic hypogonadotropic hypogonadism only with difficulty unless the misuse is reported by the user. When diagnosed, the crucial step in the therapy is the stop of anabolic use. Convalescence lasts usually several months or even more than one year. First could be seen the retreat of testicular atrophy followed by the rearrangement of spermatogenesis. The users mainly well informed from internet use for amelioration of the symptoms injections of human choriogonadotropin (hCG), selective estrogen receptor modulators (SERM) or aromatase inhibitors.Key words: anabolic steroids - doping - hypogonadotropic hypogonadism - side effects.

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...

Prolonged hypogonadism in males following withdrawal from anabolic-androgenic steroids: an under-recognized problem.

PubMed

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

2015-05-01

To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Cross-sectional, naturalistic. Out-patient facility. 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 physiological testosterone replacement, leaving 19 untreated users for the numerical comparisons below. 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). 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: 95% CI = 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: 95% CI = 2.4 (1.3, 3.4) points on a 10-point scale; P < 0.001]. In the overall group of 24 treated plus untreated former users, seven (29%) had experienced major depressive episodes during AAS withdrawal; four 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. Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged and associated with substantial morbidity. © 2015 Society for the Study of Addiction.

Self-Perceived Weight and Anabolic Steroid Misuse Among US Adolescent Boys

PubMed Central

Jampel, Jonathan D.; Murray, Stuart B.; Griffiths, Scott; Blashill, Aaron J.

2016-01-01

Purpose Anabolic steroid misuse is a growing concern among adolescent boys, and chronic misuse is associated with multisystemic health consequences. However, little is known about weight related predictors of anabolic steroid misuse. We examined the prediction of lifetime anabolic steroid misuse as a function of self-perceived weight status among US adolescent boys. Methods Analysis was undertaken using the 2013 Youth Risk Behavior Survey, a nationally representative data set sampling public and private high school students throughout the United States. Data from a total of 6,000 US adolescent boys were used in the present study. Results The prevalence of ever misusing anabolic androgenic steroids was 12.6% among boys who viewed themselves as very underweight, 11.9% for boys who viewed themselves as very overweight, compared with 3.8% for boys who viewed themselves as about the right weight. Compared to boys who viewed themselves as about the right weight, boys who self-perceived themselves as very underweight (adjusted odds ratio = 6.9, 95% confidence interval: 2.7–17.7, p < .001) and very overweight (adjusted odds ratio = 3.8, 95% confidence interval: 1.8–7.7, p < .001) were significantly associated with increased risk of anabolic androgenic steroid misuse. Conclusions Large effect size estimates were revealed, suggesting that anabolic androgenic steroid misuse is not solely a function of boys desiring increased mass; boys who desire leanness are also likely to misuse anabolic androgenic steroids. Future prevention efforts should target not only boys who view themselves as underweight but also those who perceive themselves as overweight. PMID:26598061

Multisubstance use as a feature of addiction to anabolic-androgenic steroids.

PubMed

Skarberg, Kurt; Nyberg, Fred; Engstrom, Ingemar

2009-01-01

The aim of this study was to explore and describe total drug use among anabolic-androgenic steroid (AAS) users and the reasons given for the use of these drugs. The study was based on semi-structured interviews and questionnaires involving 32 patients who were attending an addiction centre in Orebro, Sweden, for AAS use. The results indicated that a history of polysubstance use among the patients was frequent. Over half were using drugs of abuse and also taking various other pharmaceuticals. Almost half of the patients took human growth hormones, and almost half of the interviewed persons were drinking alcohol to a hazardous or harmful extent. The most common reason given for taking AAS and other hormones was to increase muscle mass and strength, but some participants also used insulin as a means of losing fat. Cannabis was used to improve sleep, heroin to decrease pain and amphetamine to increase endurance and burn fat. Our data suggest that most of the current AAS users who have been admitted to a treatment programme are multiple drug users with polysubstance dependence. The study stresses the importance of carefully examining total drug use as part of the assessment regimen for this group. 2009 S. Karger AG, Basel.

[Calciotropic actions of parathyroid hormone and vitamin D-endocrine system].

PubMed

Avila, Euclides; Barrera, David; Díaz, Lorenza

2007-01-01

Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)zD] participate in systemic regulation of calcium homeostasis through endocrine effects mediated via the specific receptors PTHR1 and VDR, expressed in bone, kidney, intestine and parathyroid glands. In bone, both hormones PTH and 1,25-(OH)2D promote calcium release into the circulation; however, they also have anabolic effects in this tissue. In kidney, PTH controls 1,25-(OH)2D synthesis, and together both hormones stimulate calcium reabsorption. The most important calciotropic action of 1,25-(OH)2D is stimulation of intestinal calcium absorption. In the parathyroid glands, 1,25-(OH)2D regulates PTH synthesis through a negative feedback mechanism, while modulating the gland growth. Finally, a general overview of the maternal adaptations regarding calcium homeostasis during pregnancy and lactation is presented.

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.

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.

Vasopressin Differentially Modulates Aggression and Anxiety in Adolescent Hamsters Administered Anabolic Steroids

PubMed Central

Morrison, Thomas R.; Ricci, Lesley A.; Melloni, Richard H.

2016-01-01

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. PMID:27149949

A review of designer anabolic steroids in equine sports.

PubMed

Waller, Christopher C; McLeod, Malcolm D

2017-09-01

In recent years, the potential for anabolic steroid abuse in equine sports has increased due to the growing availability of designer steroids. These compounds are readily accessible online in 'dietary' or 'nutritional' supplements and contain steroidal compounds which have never been tested or approved as veterinary agents. They typically have unusual structures or substitution and as a result may pass undetected through current anti-doping screening protocols, making them a significant concern for the integrity of the industry. Despite considerable focus in human sports, until recently there has been limited investigation into these compounds in equine systems. To effectively respond to the threat of designer steroids, a detailed understanding of their metabolism is needed to identify markers and metabolites arising from their misuse. A summary of the literature detailing the metabolism of these compounds in equine systems is presented with an aim to identify metabolites suitable for incorporation into screening protocols by anti-doping laboratories. The future of equine anti-doping research is likely to be guided by the incorporation of alternate testing matrices into routine screening, the improvement of in vitro technologies that can mimic in vivo equine metabolism, and the improvement of instrumentation or analytical methods that allow for the development of untargeted screening, and metabolomics approaches for use in anti-doping screening protocols. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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 seeking...

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 seeking...

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 seeking...

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 seeking...

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...

Perfluorinated compounds affect the function of sex hormone receptors.

PubMed

Kjeldsen, Lisbeth Stigaard; Bonefeld-Jørgensen, Eva Cecilie

2013-11-01

Perfluorinated compounds (PFCs) are a large group of chemicals used in different industrial and commercial applications. Studies have suggested the potential of some PFCs to disrupt endocrine homeostasis, increasing the risk of adverse health effects. This study aimed to elucidate mechanisms behind PFC interference with steroid hormone receptor functions. Seven PFCs [perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA)] were analyzed in vitro for their potential to affect estrogen receptor (ER) and androgen receptor (AR) transactivity as well as aromatase enzyme activity. The PFCs were assessed as single compounds and in an equimolar mixture. PFHxS, PFOS and PFOA significantly induced the ER transactivity, whereas PFHxS, PFOS, PFOA, PFNA and PFDA significantly antagonized the AR activity in a concentration-dependent manner. Moreover, PFDA weakly decreased the aromatase activity at a high test concentration. A mixture effect more than additive was observed on AR function. We conclude that five of the seven PFCs possess the potential in vitro to interfere with the function of the ER and/or the AR. The observed mixture effect emphasizes the importance of considering the combined action of PFCs in future studies to assess related health risks.

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 J.; 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.

The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones

PubMed Central

Maggio, Marcello; De Vita, Francesca; Fisichella, Alberto; Lauretani, Fulvio; Ticinesi, Andrea; Ceresini, Graziano; Cappola, Anne; Ferrucci, Luigi; Ceda, Gian Paolo

2015-01-01

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals. PMID:26779261

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.

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.

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

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.

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

Anabolic steroid abuse and tooth size-arch dimensions in the rat.

PubMed

Barrett, R L; Harris, E F; Tolley, E A; Nutting, D F

1993-01-01

Anabolic steroids are misused by adolescents and adults to increase muscle mass and improve appearance and athletic performance. Since anabolics strongly enhance protein synthesis, it was speculated that alterations in tooth size and arch length could occur. This study quantified the effects of the anabolic steroid nandrolone phenpropionate on these parameters in a rat model. The steroid significantly increased mandibular arch length. No difference in mesiodistal dimensions of the molars occurred. In consequence, the increased arch dimensions combined with unaltered tooth size may result in dental spacing and/or other malocclusions.

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…

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.

Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

PubMed

Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

2018-04-01

Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

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

High-Frequency Neuromuscular Electrical Stimulation Increases Anabolic Signaling.

PubMed

Mettler, Joni A; Magee, Dillon M; Doucet, Barbara M

2018-03-16

Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation settings to increase muscle mass and strength. However, the effects of NMES on muscle growth are not clear and no human studies have compared anabolic signaling between low-frequency (LF-) and high-frequency (HF-) NMES. The purpose of this study was to determine the skeletal muscle anabolic signaling response to an acute bout of LF- and HF-NMES. Eleven young healthy volunteers (6 men; 5 women) received an acute bout of LF- (20 Hz) and HF- (60 Hz) NMES. Muscle biopsies were obtained from the vastus lateralis muscle prior to the first NMES treatment and 30-mins following each NMES treatment. Phosphorylation of the following key anabolic signaling proteins was measured by Western blot and proteins are expressed as a ratio of phosphorylated to total: mammalian target of rapamycin (mTOR), p70-S6 kinase 1 (S6K1), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Compared to Pre-NMES, phosphorylation of mTOR was upregulated 40.2% for LF-NMES (P = 0.018) and 68.4% for HF-NMES (P < 0.0001) and HF-NMES was 29.3% greater than LF-NMES (P = 0.026). Phosphorylation of S6K1 after HF-NMES was 96.6% higher than Pre-NMES (P = 0.001), was not different between Pre-NMES and LF-NMES (although was 50.4% higher after LF-) or LF- and HF-NMES (P > 0.05). There were no differences between treatment conditions for 4E-BP1 phosphorylation (P > 0.05). An acute bout of LF- and HF-NMES upregulated anabolic signaling with HF-NMES producing a greater anabolic response compared to LF-NMES, suggesting that HF-stimulation may provide a stronger stimulus for processes that initiate muscle hypertrophy. Additionally, the stimulation frequency parameter should be considered by clinicians in the design of optimal NMES treatment protocols.

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.

Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users: A Systematic Review and Meta-Analysis.

PubMed

Christou, Maria A; Christou, Panagiota A; Markozannes, Georgios; Tsatsoulis, Agathocles; Mastorakos, George; Tigas, Stelios

2017-09-01

Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system. This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users. An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation. Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation

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.

Anabolic steroids for the treatment of weight loss in HIV-infected individuals.

PubMed

Johns, K; Beddall, M J; Corrin, R C

2005-10-19

Individuals with HIV infection often lose weight during the course of their disease. Furthermore, low serum concentrations of testosterone are common in individuals with HIV infection, particularly those with weight loss. Treatment of weight loss with anabolic steroids in HIV-infected individuals may be beneficial. Our objectives were to assess the efficacy and safety of anabolic steroids for the treatment of weight loss in adults with HIV infection. We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, AIDSLINE, AIDSearch, EMBASE, CINAHL, Current Contents, and the National Library of Medicine Gateway Abstracts for controlled trials up to April 2005. We also searched the bibliographies of the identified studies and review the articles. In addition, pharmaceutical manufacturers of anabolic steroids were contacted. Randomized controlled trials that compared the use of an anabolic steroid to placebo to treat weight loss in adults with HIV were included. Randomized controlled trials that compared the use of anabolic steroids to placebo for the treatment of weight loss in adults with HIV were selected. Change from baseline in lean body mass or in body weight was reported as on outcome measure. Two reviewers independently assessed the trials for quality of randomization, blinding, withdrawals, and adequacy of allocation concealment. For continuous data, weighted mean differences (WMD) were calculated. For dichotomous outcomes, risk differences, were calculated. Because of uncertainty as to whether consistent true effects exist in such different populations and treatments, the authors decided a priori to use random effects models for all outcomes. Thirteen trials met the inclusion criteria. Two hundred ninety-four individuals randomized to anabolic steroid therapy and 238 individuals randomized to placebo were included in the analysis of efficacy for change from baseline in lean body mass. Three hundred forty

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

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

Linking Cancer Cachexia-Induced Anabolic Resistance to Skeletal Muscle Oxidative Metabolism

PubMed Central

Montalvo, Ryan N.

2017-01-01

Cancer cachexia, a wasting syndrome characterized by skeletal muscle depletion, contributes to increased patient morbidity and mortality. While the intricate balance between protein synthesis and breakdown regulates skeletal muscle mass, the suppression of basal protein synthesis may not account for the severe wasting induced by cancer. Therefore, recent research has shifted to the regulation of “anabolic resistance,” which is the impaired ability of nutrition and exercise to stimulate protein synthesis. Emerging evidence suggests that oxidative metabolism can regulate both basal and induced muscle protein synthesis. While disrupted protein turnover and oxidative metabolism in cachectic muscle have been examined independently, evidence suggests a linkage between these processes for the regulation of cancer-induced wasting. The primary objective of this review is to highlight the connection between dysfunctional oxidative metabolism and cancer-induced anabolic resistance in skeletal muscle. First, we review oxidative metabolism regulation of muscle protein synthesis. Second, we describe cancer-induced alterations in the response to an anabolic stimulus. Finally, we review a role for exercise to inhibit cancer-induced anabolic suppression and mitochondrial dysfunction. PMID:29375734

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.

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.

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.

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.

Sudden cardiac arrest following ventricular fibrillation attributed to anabolic steroid use in an adolescent.

PubMed

Lichtenfeld, Jana; Deal, Barbara J; Crawford, Susan

2016-06-01

Anabolic androgenic steroids are synthetic derivatives of testosterone that promote the growth of skeletal muscles and have many recognised cardiovascular effects. We report the clinical presentation and pathological findings of an adolescent male whose sudden cardiac arrest following ventricular fibrillation was attributed to anabolic androgenic steroid use. The age of our patient reflects the usage of anabolic androgenic steroids among younger athletes and highlights the need for increased awareness among practitioners.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

The Central Effects of Androgenic-anabolic Steroid Use.

PubMed

Mędraś, Marek; Brona, Anna; Jóźków, Paweł

: Millions of men use androgenic-anabolic steroids (AAS) to stimulate muscle growth and improve physical appearance. Although 1 out of 3 people who uses androgenic-anabolic steroids develops a steroid use disorder, the effects of the drugs on the central nervous system and the psyche are still not well understood. Although most addictive substances improve mood immediately after administration, AAS exert less pronounced euphoric effects. Instead, they are primarily taken for the delayed gratification of increased muscle mass. Withdrawal from AAS may lead to a range of somatic and psychiatric symptoms, and, in many cases, comprehensive treatment supervised by an endocrinologist and a psychiatrist is required.

Position stand on androgen and human growth hormone use.

PubMed

Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

2009-08-01

Hoffman, JR, Kraemer, WJ, Bhasin, S, Storer, T, Ratamess, NA, Haff, GG, Willoughby, DS, and Rogol, AD. Position stand on Androgen and human growth hormone use. J Strength Cond Res 23(5): S1-S59, 2009-Perceived yet often misunderstood demands of a sport, overt benefits of anabolic drugs, and the inability to be offered any effective alternatives has fueled anabolic drug abuse despite any consequences. Motivational interactions with many situational demands including the desire for improved body image, sport performance, physical function, and body size influence and fuel such negative decisions. Positive countermeasures to deter the abuse of anabolic drugs are complex and yet unclear. Furthermore, anabolic drugs work and the optimized training and nutritional programs needed to cut into the magnitude of improvement mediated by drug abuse require more work, dedication, and preparation on the part of both athletes and coaches alike. Few shortcuts are available to the athlete who desires to train naturally. Historically, the NSCA has placed an emphasis on education to help athletes, coaches, and strength and conditioning professionals become more knowledgeable, highly skilled, and technically trained in their approach to exercise program design and implementation. Optimizing nutritional strategies are a vital interface to help cope with exercise and sport demands (). In addition, research-based supplements will also have to be acknowledged as a strategic set of tools (e.g., protein supplements before and after resistance exercise workout) that can be used in conjunction with optimized nutrition to allow more effective adaptation and recovery from exercise. Resistance exercise is the most effective anabolic form of exercise, and over the past 20 years, the research base for resistance exercise has just started to develop to a significant volume of work to help in the decision-making process in program design (). The interface with nutritional strategies has been less

Anabolic Heterogeneity Following Resistance Training: A Role for Circadian Rhythm?

PubMed

Camera, Donny M

2018-01-01

It is now well established that resistance exercise stimulates muscle protein synthesis and promotes gains in muscle mass and strength. However, considerable variability exists following standardized resistance training programs in the magnitude of muscle cross-sectional area and strength responses from one individual to another. Several studies have recently posited that alterations in satellite cell population, myogenic gene expression and microRNAs may contribute to individual variability in anabolic adaptation. One emerging factor that may also explain the variability in responses to resistance exercise is circadian rhythms and underlying molecular clock signals. The molecular clock is found in most cells within the body, including skeletal muscle, and principally functions to optimize the timing of specific cellular events around a 24 h cycle. Accumulating evidence investigating the skeletal muscle molecular clock indicates that exercise-induced contraction and its timing may regulate gene expression and protein synthesis responses which, over time, can influence and modulate key physiological responses such as muscle hypertrophy and increased strength. Therefore, the circadian clock may play a key role in the heterogeneous anabolic responses with resistance exercise. The central aim of this Hypothesis and Theory is to discuss and propose the potential interplay between the circadian molecular clock and established molecular mechanisms mediating muscle anabolic responses with resistance training. This article begins with a current review of the mechanisms associated with the heterogeneity in muscle anabolism with resistance training before introducing the molecular pathways regulating circadian function in skeletal muscle. Recent work showing members of the core molecular clock system can regulate myogenic and translational signaling pathways is also discussed, forming the basis for a possible role of the circadian clock in the variable anabolic responses with

Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.

PubMed

Higuchi, Robert I; Arienti, Kristen L; López, Francisco J; Mani, Neelakhanda S; Mais, Dale E; Caferro, Thomas R; Long, Yun Oliver; Jones, Todd K; Edwards, James P; Zhi, Lin; Schrader, William T; Negro-Vilar, Andrés; Marschke, Keith B

2007-05-17

Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound (R)-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, (R)-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.

Multifunctional receptor model for dioxin and related compound toxic action: possible thyroid hormone-responsive effector-linked site.

PubMed Central

McKinney, J D

1989-01-01

Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones. Images FIGURE 3. A FIGURE 3. B FIGURE 3. C FIGURE 3. D PMID:2551666

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.

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.

Parathyroid Hormone-Related Protein, Its Regulation of Cartilage and Bone Development, and Role in Treating Bone Diseases.

PubMed

Martin, T John

2016-07-01

Although parathyroid hormone-related protein (PTHrP) was discovered as a cancer-derived hormone, it has been revealed as an important paracrine/autocrine regulator in many tissues, where its effects are context dependent. Thus its location and action in the vasculature explained decades-long observations that injection of PTH into animals rapidly lowered blood pressure by producing vasodilatation. Its roles have been specified in development and maturity in cartilage and bone as a crucial regulator of endochondral bone formation and bone remodeling, respectively. Although it shares actions with parathyroid hormone (PTH) through the use of their common receptor, PTHR1, PTHrP has other actions mediated by regions within the molecule beyond the amino-terminal sequence that resembles PTH, including the ability to promote placental transfer of calcium from mother to fetus. A striking feature of the physiology of PTHrP is that it possesses structural features that equip it to be transported in and out of the nucleus, and makes use of a specific nuclear import mechanism to do so. Evidence from mouse genetic experiments shows that PTHrP generated locally in bone is essential for normal bone remodeling. Whereas the main physiological function of PTH is the hormonal regulation of calcium metabolism, locally generated PTHrP is the important physiological mediator of bone remodeling postnatally. Thus the use of intermittent injection of PTH as an anabolic therapy for bone appears to be a pharmacological application of the physiological function of PTHrP. There is much current interest in the possibility of developing PTHrP analogs that might enhance the therapeutic anabolic effects. Copyright © 2016 the American Physiological Society.

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

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.

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 ...

Excretion of the anabolic steroid boldenone by racing pigeons.

PubMed

Hagedorn, H W; Zankl, H; Grund, C; Schulz, R

1997-03-01

To detect the anabolic steroid bolden-one and to monitor its elimination in the droppings (hereafter referred to as feces) of pigeons treated with the drug. 8 female pigeons ("Texas" race, 500 +/- 20 g). 4 pigeons were given boldenone-17-undecylenate (10 mg/kg of body weight, IM). Feces were collected over defined periods, freeze-dried, extracted with buffer (pH 7.2), and centrifuged. Total immunoreactivity in the supernatant was determined directly by use of an ELISA, and individual boldenone concentration was measured by use of a high-performance liquid chromatography (HPLC)/ELISA after solvent extraction of the aqueous phase. An additional 4 pigeons received a 1-mg/kg dose of the drug. Screening of feces from boldenone-treated pigeons revealed detection of the drug up to 49 days after its administration. The free parent compound was detected during the same period at a constant value of 12 ng/g of lyophilized feces. Positive results predicted by screening were reliably confirmed by the HPLC/ ELISA. Treatment of pigeons with a lower dosage (1 mg/kg) yielded positive results for 31 days. Illegal medication of pigeons with the anabolic steroid boldenone can be uncovered by screening of feces, using a specific ELISA. Confirmation analysis by use of 2 HPLC systems combined with ELISA reliably yields evidence of drug misuse. Owing to the multiple immunoreactive material, the apparent boldenone concentrations registered by screening markedly exceeded the immunoreactivity attributed to boldenone recovered by HPLC/ELISA. Because the test yields positive results in pigeons for at least 31 days after a single treatment, even at a low dosage of the 17-undecylenate preparation (1 mg/kg), the proposed boldenone test procedure is recommended for doping control in racing pigeons.

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

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%�

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.

Effects of anabolic steroids on chronic obstructive pulmonary disease: a meta-analysis of randomised controlled trials.

PubMed

Pan, Lei; Wang, Manyuan; Xie, Xiaomei; Du, Changjun; Guo, Yongzhong

2014-01-01

Anabolic steroids are known to improve body composition and muscle strength in healthy people. However, whether anabolic steroids improve the physical condition and function in patients with chronic obstructive pulmonary disease (COPD) remains undetermined. A meta-analysis was conducted to review the current evidence regarding the effects of anabolic steroids on COPD patients. A comprehensive literature search of PubMed and EMBASE was performed to identify randomised controlled trials that examine the effects of anabolic steroids on COPD patients. Weighted mean differences (WMDs) with 95% confidence intervals were calculated to determine differences between anabolic steroid administration and control conditions. Eight eligible studies involving 273 COPD patients were identified in this meta-analysis. Significant improvements were found in body weight (0.956 kg), fat-free mass (1.606 kg), St. George's Respiratory Questionnaire total score (-6.336) and symptom score (-12.148). The apparent improvements in maximal inspiratory pressure (2.740 cmH2O) and maximal expiratory pressure (12.679 cmH2O) were not significant. The effects on handgrip strength, forced expiratory volume in one second (FEV1), predicted FEV1 percent, PaO2, PaCO2 and six-min walk distance were negative, with WMDs of -0.245 kg, -0.096 L/sec, -1.996% of predicted, -1.648 cmHg, -0.039 cmHg and -16.102 meters, respectively. Limited evidence available from the published literature suggests that the benefit of anabolic steroids on COPD patients cannot be denied. However, further studies are needed to identify the specific benefits and adverse effects of anabolic steroids on COPD patients and to determine the optimal populations and regimes of anabolic steroids in COPD patients.

Acute bile nephropathy secondary to anabolic steroids.

PubMed

Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

2016-02-01

Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Menopausal Symptom Relief and Side Effects Experienced by Women Using Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 1.

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. The results of this study will be summarized in forthcoming articles in this series. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

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

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed Central

Guo, Yongzhong

2014-01-01

Background Anabolic steroids are known to improve body composition and muscle strength in healthy people. However, whether anabolic steroids improve the physical condition and function in patients with chronic obstructive pulmonary disease (COPD) remains undetermined. A meta-analysis was conducted to review the current evidence regarding the effects of anabolic steroids on COPD patients. Methods A comprehensive literature search of PubMed and EMBASE was performed to identify randomised controlled trials that examine the effects of anabolic steroids on COPD patients. Weighted mean differences (WMDs) with 95% confidence intervals were calculated to determine differences between anabolic steroid administration and control conditions. Results Eight eligible studies involving 273 COPD patients were identified in this meta-analysis. Significant improvements were found in body weight (0.956 kg), fat-free mass (1.606 kg), St. George's Respiratory Questionnaire total score (−6.336) and symptom score (−12.148). The apparent improvements in maximal inspiratory pressure (2.740 cmH2O) and maximal expiratory pressure (12.679 cmH2O) were not significant. The effects on handgrip strength, forced expiratory volume in one second (FEV1), predicted FEV1 percent, PaO2, PaCO2 and six-min walk distance were negative, with WMDs of −0.245 kg, −0.096 L/sec, −1.996% of predicted, −1.648 cmHg, −0.039 cmHg and −16.102 meters, respectively. Conclusions Limited evidence available from the published literature suggests that the benefit of anabolic steroids on COPD patients cannot be denied. However, further studies are needed to identify the specific benefits and adverse effects of anabolic steroids on COPD patients and to determine the optimal populations and regimes of anabolic steroids in COPD patients. PMID:24427297

Development of genetically engineered bacteria for production of selected aromatic compounds

DOEpatents

Ward, Thomas E.; Watkins, Carolyn S.; Bulmer, Deborah K.; Johnson, Bruce F.; Amaratunga, Mohan

2001-01-01

The cloning and expression of genes in the common aromatic pathway of E. coli are described. A compound for which chorismate, the final product of the common aromatic pathway, is an anabolic intermediate can be produced by cloning and expressing selected genes of the common aromatic pathway and the genes coding for enzymes necessary to convert chorismate to the selected compound. Plasmids carrying selected genes of the common aromatic pathway are also described.

Body image, disordered eating and anabolic steroid use in female bodybuilders.

PubMed

Goldfield, Gary S

2009-01-01

Body dissatisfaction and unhealthy eating practices are common among sports and activities that require low body fat or low body weight for enhanced performance. Competitive Bodybuilding is a sport that requires participants to be exceptionally lean and mesomorphic, thus participants may be vulnerable to developing unhealthy eating and weight control practices, as well as using anabolic steroids. This study compares competitive female bodybuilders (CFBBs) and recreational female weight-training controls (RFWTs) on a broad scope of eating related and general psychological characteristics. Anonymous questionnaires, designed to assess eating attitudes, body image, weight and shape preoccupation, prevalence of binge eating, body modification practices (including anabolic steroids), lifetime rates of eating disorders, and general psychological characteristics, were completed by 20 CFBBs and 25 RFWTs. High rates of weight and shape preoccupation, body dissatisfaction, bulimic practices, and anabolic steroid use were reported among CFBBs, and to a lesser degree, RFWTs. Differences between groups on general psychological factors were not statistically significant and effect sizes were small. CFBBs appear to share many eating-related features with women with bulimia nervosa but few psychological traits. Longitudinal research is needed to ascertain whether women with disordered eating or a history of bulimia nervosa disproportionately gravitate to competitive bodybuilding, and/or whether competitive bodybuilding fosters body dissatisfaction, disordered eating, bulimia nervosa, and anabolic steroid use.

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Novel orally active growth hormone secretagogues.

PubMed

Hansen, T K; Ankersen, M; Hansen, B S; Raun, K; Nielsen, K K; Lau, J; Peschke, B; Lundt, B F; Thøgersen, H; Johansen, N L; Madsen, K; Andersen, P H

1998-09-10

A novel class of growth hormone-releasing compounds with a molecular weight in the range from 500 to 650 has been discovered. The aim of this study was to obtain growth hormone secretagogues with oral bioavailability. By a rational approach we were able to reduce the size of the lead compound ipamorelin (4) and simultaneously to reduce hydrogen-bonding potential by incorporation of backbone isosters while retaining in vivo potency in swine. A rat pituitary assay was used for screening of all compounds and to evaluate which compounds should be tested further for in vivo potency in swine and oral bioavailability, fpo, in dogs. Most of the tested compounds had fpo in the range of 10-55%. In vivo potency in swine after iv dosing is reported, and ED50 was found to be 30 nmol/kg of body weight for the most potent compound.

Growth hormone, IGF-I and insulin and their abuse in sport

PubMed Central

Holt, R I G; Sönksen, P H

2008-01-01

There is widespread anecdotal evidence that growth hormone (GH) is used by athletes for its anabolic and lipolytic properties. Although there is little evidence that GH improves performance in young healthy adults, randomized controlled studies carried out so far are inadequately designed to demonstrate this, not least because GH is often abused in combination with anabolic steroids and insulin. Some of the anabolic actions of GH are mediated through the generation of insulin-like growth factor-I (IGF-I), and it is believed that this is also being abused. Athletes are exposing themselves to potential harm by self-administering large doses of GH, IGF-I and insulin. The effects of excess GH are exemplified by acromegaly. IGF-I may mediate and cause some of these changes, but in addition, IGF-I may lead to profound hypoglycaemia, as indeed can insulin. Although GH is on the World Anti-doping Agency list of banned substances, the detection of abuse with GH is challenging. Two approaches have been developed to detect GH abuse. The first is based on an assessment of the effect of exogenous recombinant human GH on pituitary GH isoforms and the second is based on the measurement of markers of GH action. As a result, GH abuse can be detected with reasonable sensitivity and specificity. Testing for IGF-I and insulin is in its infancy, but the measurement of markers of GH action may also detect IGF-I usage, while urine mass spectroscopy has begun to identify the use of insulin analogues. PMID:18376417

The relationship between anabolic androgenic steroids and muscle dysmorphia: a review.

PubMed

Rohman, Lebur

2009-01-01

This review explores the condition of muscle dysmorphia (MD) and its relationship with anabolic androgenic steroids (AAS). Particular emphasis is placed upon whether anabolic steroids are a predisposing, precipitating or perpetuating factor of MD. Furthermore, psychiatric complications of AAS abuse are examined. The current evidence from the literature suggests that AAS (ab)use is possibly a perpetuating factor in the evolution of MD. Psychiatric complications of AAS include mood and behavior changes, perceptual abnormalities, and withdrawal symptoms. In addition, there appears to be a credible dependence theory to AAS in fruition.

Juvenile Hormone Induction of Esterases: A Mechanism for the Regulation of Juvenile Hormone Titer

PubMed Central

Whitmore, Donald; Whitmore, Elaine; Gilbert, Lawrence I.

1972-01-01

Within a few hours after injection of juvenile hormone into Hyalophora gloveri pupae, several fast-migrating carboxylesterases (EC 3.1.1.1) that are sensitive to diisopropylfluorophosphate appear in the hemolymph. Treatment of the pupae with puromycin or actinomycin D prevents the appearance of these hemolymph enzymes, suggesting de novo synthesis of the carboxylesterases. Of the several other compounds investigated, only a potent mimic of the juvenile hormone is able to induce these enzymes. When the induced enzymes are incubated in vitro with 14C-labeled juvenile hormone, the hormone is rapidly and efficiently degraded. It is suggested that these induced carboxylesterases play an important role in the regulation of juvenile hormone titer. Images PMID:4504374

Anabolic Steroid Reversal of Denervation Atrophy

DTIC Science & Technology

2012-03-01

rabbit model treated with nandrolone decanoate12 and Zhao et al. found that nandrolone significantly reduced chronic denervation atrophy (but not acute...surprising results, the most important question is whether the concept of augmenting reinnervated muscle is flawed or whether nandrolone (at the dosage...administration of supraphysiological doses of anabolic or natural steroids to normal rats22, 23. Egginton administered nandrolone to sedentary female

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

PubMed Central

dos Santos, Marcelo R.; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; de Souza, Francis R.; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population. PMID:29791601

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users.

PubMed

Santos, Marcelo R Dos; Sayegh, Ana L C; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R de; Toschi-Dias, Edgar; Bortolotto, Luiz A; Yonamine, Mauricio; Negrão, Carlos E; Alves, Maria-Janieire N N

2018-05-21

Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder.

PubMed

Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

2009-06-21

Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

Adolescent Anabolic/Androgenic Steroids: Aggression and Anxiety During Exposure Predict Behavioral Responding During Withdrawal in Syrian Hamsters (Mesocricetus auratus)

PubMed Central

Ricci, Lesley A.; Morrison, Thomas R.; Melloni, Richard H.

2014-01-01

In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety- eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. PMID:24126136

The effect of nandrolone, an anabolic steroid on putrescine metabolism in the mouse.

PubMed Central

Henningsson, S; Rosengren, E

1976-01-01

1 The catabolism of injected 14 C-putrescine was studied in mice treated with nandrolone phenpropionate, an anabolic steroid. 2 The putrescine was rapidly metabolized; almost 50% of the injected radioactivity was recovered within 2 h as 14 CO2 in the expired air. 3 Considerable amounts of radioactive gamma-aminobutyric acid (GABA) and an unidentified compound were found in the kidney and in the urine in addition to radioactive putrescine, spermidine and spermine both in controls and nandrolone-treated mice. 4 Nandrolone elevated the concentration of endogenous putrescine in the kidney and urine, eightfold and twentyfold, respectively, and the concentrations of spermidine and spermine were also increased 5 after the injection of 14C-putrescine the incorporation of 14C into spermidine was significantly increased in the kidney of mice receiving nandrolone. PMID:990594

Hidden Danger of Irrational Abusing Illegal Androgenic-anabolic Steroids in Recreational Athletes Age Under 35 in Bosnia & Herzegovina.

PubMed

Solakovic, Sid; Totic, Dragan; Vukas, Haris; Djedovic, Muhamed

2015-06-01

Androgenic-anabolic steroids are rarely used by sportsmen who want to improve physical performance in competition sport. Despite that they are well aware of the side effects of anabolic steroids, many young athletes in Bosnia and Herzegovina without competition motivation come in temptation, trying to achieve better muscle proportion and physical performance unknowing consequence of side effects and what is hiding behind. Risk factors such as increasing of lipid levels and arterial hypertension are major factors which have important role in the Pathogenesis of atherosclerosis and are responsible for occurrence of cardiovascular disease even causing a sudden death in young athletes. The aim of the study was to estimate the frequency of misusing of androgenic anabolic steroid drugs in young recreational sportsmen without competition motivation. This study will try to estimate vascular and lipid status, analyzing the side effects of steroids in young recreational athletes under the age of 35, in Bosnia and Herzegovina. The study included 70 individuals in period of 2010 till 2015 on recreational exercising program; 35 individuals misusing androgenic anabolic steroids during the period of 5 years were compared with 35 individuals which do not use androgenic anabolic steroids. Non-invasive methods were used in all individual (clinical examination and vascular ultrasound examination of vein system). The routine of training units in both groups was approximately two hours 4-6 times per week. Final analysis has reveal that in androgenic anabolic steroids group in 18 individuals or 55.7% arterial hypertension with hyperlipidemia was more represented, compared with the group without using anabolic steroids, represented by 2 individuals or 5.7% and it was statistically considered significant by using p value less than 0.05. (p<0.05). Statistically dominant population using anabolic steroids drugs are males (100%) or 35 individuals; we did not find females using anabolic

Multi-organ damage induced by anabolic steroid supplements: a case report and literature review

PubMed Central

Samaha, Ali A; Nasser-Eddine, Walid; Shatila, Elizabeth; Haddad, John J; Wazne, Jaafar; Eid, Ali H

2008-01-01

Introduction The use of anabolic supplements and other related drugs for body building and to enhance athletic performance is nowadays widespread and acutely pervasive all around the world. This alarming increase in the use of anabolic and amino acid supplements has been linked to a diverse array of pathologies. As previously reported, the abuse of androgenic steroids is not without severe physiological, psychiatric and physical costs. The case we report here describes multi-organ damage resulting from the abuse and uncontrolled use of anabolic steroid supplements, mainly testosterone. Case presentation A 24-year-old white man presented with abdominal pain concomitant with nausea and vomiting. Laboratory analysis revealed hypercalcemia, elevated liver enzymes and high levels of amylase, lipase and creatine protein kinase. Conclusion Amino acid as well as anabolic supplements may lead to abnormal functioning of many organs, which could be fatal in some instances. This mandates worldwide and concerted efforts to educate the public, especially the youth, about the dangers of these increasingly abused drugs. PMID:18976461

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.

Neuropsychiatric effects of anabolic steroids in male normal volunteers.

PubMed

Su, T P; Pagliaro, M; Schmidt, P J; Pickar, D; Wolkowitz, O; Rubinow, D R

1993-06-02

To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers. A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone. An inpatient research unit at the National Institutes of Health. A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use. A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal. Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures. Significant (P < .05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes. This is the first placebo-controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids.

Attenuation of Posttraumatic Muscle Catabolism and Osteopenia by Long-Term Growth Hormone Therapy

PubMed Central

Hart, David W.; Herndon, David N.; Klein, Gordon; Lee, Steven B.; Celis, Mario; Mohan, Subburaman; Chinkes, David L.; Wolf, Steven E.

2001-01-01

Objective To determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn. Summary Background Data The hypermetabolic response to severe burn is associated with increased energy expenditure, insulin resistance, immunodeficiency, and whole body catabolism that persists for months after injury. Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses. Methods Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone (0.05 mg/kg per day) on muscle accretion and bone growth. Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn. Total body weight, height, dual-energy x-ray absorptiometry, indirect calorimetry, and hormone values were measured at discharge, then at 6 months, 9 months, and 12 months after burn. Results were compared between groups. Results Growth hormone subjects gained more weight than placebo subjects at the 9-month study point; this disparity in weight gain continued to expand throughout the remainder of the study. Height also increased in the growth hormone group compared with controls at 12 months. Change in lean body mass was greater in those treated with growth hormone at 6, 9, and 12 months. Bone mineral content was increased at 9 and 12 months; this was associated with higher parathormone levels. Conclusions Low-dose recombinant human growth hormone successfully abates muscle catabolism and osteopenia induced by severe burn. PMID:11371741

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.

Anabolic steroid-induced hypogonadism: diagnosis and treatment.

PubMed

Rahnema, Cyrus D; Lipshultz, Larry I; Crosnoe, Lindsey E; Kovac, Jason R; Kim, Edward D

2014-05-01

To develop an understanding of hypogonadal men with a history of anabolic-androgenic steroid (AAS) use and to outline recommendations for management. Review of published literature and expert opinions. Intended as a meta-analysis, but no quality studies met the inclusion criteria. Not applicable. Men seeking treatment for symptomatic hypogonadism who have used nonprescribed AAS. History and physical examination followed by medical intervention if necessary. Serum testosterone and gonadotropin levels, symptoms, and fertility restoration. Symptomatic hypogonadism is a potential consequence of AAS use and may depend on dose, duration, and type of AAS used. Complete endocrine and metabolic assessment should be conducted. Management strategies for anabolic steroid-associated hypogonadism (ASIH) include judicious use of testosterone replacement therapy, hCG, and selective estrogen receptor modulators. Although complications of AAS use are variable and patient specific, they can be successfully managed. Treatment of ASIH depends on the type and duration of AAS use. Specific details regarding a patient's AAS cycle are important in medical management. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Sarcopenia in older mice is characterized by a decreased anabolic response to a protein meal.

PubMed

van Dijk, Miriam; Nagel, Jolanda; Dijk, Francina J; Salles, Jerôme; Verlaan, Sjors; Walrand, Stephane; van Norren, Klaske; Luiking, Yvette

Ageing is associated with sarcopenia, a progressive decline of skeletal muscle mass, muscle quality and muscle function. Reduced sensitivity of older muscles to respond to anabolic stimuli, i.e. anabolic resistance, is part of the underlying mechanisms. Although, muscle parameters have been studied in mice of various ages/strains; the aim was to study if mice display similar deteriorating processes as human ageing. Therefore, 10,16,21 and 25 months-old C57BL6/6J male mice were studied to measure parameters of sarcopenia and factors contributing to its pathophysiology, with the aim of characterizing sarcopenia in old mice. Muscle mass of the hind limb was lower in 25 as compared to 10 month-old mice. A significant decrease in physical daily activity, muscle grip strength and ex vivo muscle maximal force production was observed in 25 compared to 10 month-old mice. The muscle anabolic response to a single protein meal showed increased muscle protein synthesis in young, but not in old mice, indicative to anabolic resistance. However, by increasing the protein content in meals, anabolic resistance could be overcome, similar as in human elderly. Additionally, aged mice showed higher fasted insulin and hepatic malondialdehyde (MDA) levels (=marker oxidative stress). This study shows clear characteristics of sarcopenia that coincide with anabolic resistance, insulin resistance and oxidative stress in 25 month-old C57/BL6 male mice, similar to human ageing. Furthermore, similar decline in muscle mass, strength and function was observed in this aged-mice-model. These observations offer potential for the future to explore in old mice the effects of interventions targeting sarcopenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Homeostatic signature of anabolic steroids in cattle using 1H-13C HMBC NMR metabonomics.

PubMed

Dumas, Marc-Emmanuel; Canlet, Cécile; Vercauteren, Joseph; André, François; Paris, Alain

2005-01-01

We used metabonomics to discriminate the urinary signature of different anabolic steroid treatments in cattle having different physiological backgrounds (age, sex, and race). (1)H-(13)C heteronuclear multiple bonding connectivity NMR spectroscopy and multivariate statistical methods reveal that metabolites such as trimethylamine-N-oxide, dimethylamine, hippurate, creatine, creatinine, and citrate characterize the biological fingerprint of anabolic treatment. These urinary biomarkers suggest an overall homeostatic adaptation in nitrogen and energy metabolism. From results obtained in this study, it is now possible to consider metabonomics as a complementary method usable to improve doping control strategies to detect fraudulent anabolic treatment in cattle since the oriented global metabolic response provides helpful discrimination.

Anabolic Steroid Misuse Among US Adolescent Boys: Disparities by Sexual Orientation and Race/Ethnicity.

PubMed

Blashill, Aaron J; Calzo, Jerel P; Griffiths, Scott; Murray, Stuart B

2017-02-01

To examine the prevalence of anabolic steroid misuse among US adolescent boys as a function of sexual orientation and race/ethnicity. We analyzed boys from the 2015 Youth Risk Behavior Survey (n = 6248; mean age = 16), a representative sample of US high school students. Lifetime prevalence of anabolic steroid misuse was dichotomized as never versus 1 or more times. Sexual minority boys reported elevated misuse compared with heterosexual boys, within each level of race/ethnicity. Black, Hispanic, and White sexual minority boys reported misuse at approximately 25%, 20%, and 9%, respectively. Sexual orientation health disparities in anabolic steroid misuse disproportionally affect Black and Hispanic sexual minority adolescent boys, but more research is needed to understand the mechanisms driving these disparities.

Mixed-treatment comparison of anabolic (teriparatide and PTH 1-84) therapies in women with severe osteoporosis.

PubMed

Migliore, A; Broccoli, S; Massafra, U; Bizzi, E; Frediani, B

2012-03-01

The recent development of compounds with anabolic action on bone have increased the range of therapeutic options for the treatment of osteoporosis and the prevention of fractures. Two major PTH analogs, the synthetic full-length 1-84 PTH molecule and the recombinant 1-34 N-terminal fragment (teriparatide), are available for the treatment of osteoporosis in many countries. There have bee no comparative trials on the bone anabolic effects of these compounds. In this study we applied a mixed treatment comparison (MTC) to compare the efficacy of teriparatide versus PTH 1-84 for the prevention of vertebral and non-vertebral fractures in women with severe osteoporosis. With this approach the relative treatment effect of one intervention over another can be obtained in the absence of head-to-head comparison. Among the candidate papers selected for analysis, two randomized controlled trials investigating the effects of teriparatide and PTH 1-84 met the selection criteria and underwent MTC analysis. Based on a fixed-effect MTC model analysis of data from two RCTs, teriparatide (20 µg/day) showed a 70% and 94% probability of being the best treatment for the prevention of vertebral and non-vertebral fractures, respectively. Together with a lack of statistical significance, this study has additional limitations. Some differences in trial procedures and populations exist; another limitation concerns the impossibility of carrying out a randomized-effect model MTC, due to sample exiguity. Furthermore, in order to consider unknown or unmeasured differences of covariates across trials, a random-effects approach would be preferred in order to assess the presence of heterogeneity across comparisons. In contrast, in our analysis a fixed-effect MTC model only was used. Teriparatide is expected to provide a greater efficacy over PTH 1-84 with both vertebral and non-vertebral fracture prevention in postmenopausal women with severe osteoporosis.

Phytosterol consumption and the anabolic steroid boldenone in humans: a hypothesis piloted.

PubMed

Ros, M M; Sterk, S S; Verhagen, H; Stalenhoef, A F H; de Jong, N

2007-07-01

The presence of the anabolic steroid boldenone in animals has become a research topic as its occurrence is proposed to be a marker for illegal hormone administration. However, boldenone can also be formed from beta-sitosterol, a phytosterol present in animal feed, as well as from endogenous sources. The observations in animals together with the increased consumption of phytosterol-enriched foods in the Western population led the authors to the hypothesis that consumption of phytosterol-enriched foods might possibly lead to increased boldenone levels in humans. The authors performed a pilot study among female volunteers (n = 10) to investigate whether boldenone concentrations in urine were detectable after consumption of 25 g day(-1) of phytosterol-enriched margarines for 1 week. Urine samples were collected at days 0, 3 or 4, and 7. Urine of a sitosterolemia (a rare autosomal recessively inherited lipid metabolic disorder) patient was collected as a positive control case. No traces of boldenone were detected in either the volunteers or in the patient. In conclusion, there is no evidence of formation of boldenone in women after consumption of the recommended amount of phytosterol-enriched margarines.

[Nephrocalcinosis associated with the use of anabolic steroid].

PubMed

Luchi, Weverton Machado; Ricarte, Rodrigo Nasser; Roitman, Luciana Fernandes; Santos, Omar da Rosa

2015-01-01

The anabolic steroid have been used as a therapeutic tool in various clinical conditions. However, indiscriminate use associated with other nutritional supplements has generated serious adverse effects. Male, 21 years old, admitted with nausea, fatigue, appetite loss, headache and hypertension. Blood tests showed Cr: 3.9 mg% U: 100 mg% and Total Calcium 14 mg/dl. Ultrasonography and renal biopsy were consistent with nephrocalcinosis. There has been gradual improvement in renal function and calcium levels after vigorous hydration and furosemide. However, after 1 year, renal calcium deposits persist, corticomedullary ratio reduced in ultrasound and stable creatinine of 1.4 mg/dl. Previous cases showed acute tubular necrosis and interstitial nephritis with little calcium deposits in the renal interstitium. In this case we found severe nephrocalcinosis associated with nephrosclerosis. Our objective is to report the occurrence of acute kidney Injury with nephrocalcinosis associated with use of anabolic steroid and provide a review of the matter.

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

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

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

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.

[Growth hormone: a magical potion?].

PubMed

Schlienger, J L; Goichot, B

1998-04-01

The various components of the growth hormone (GH)-insulin-like growth factor (IGF-I) axis and their binding proteins have many peripheral effects, mainly on bone, growth, activation of main cellular functions, energy metabolism and protein anabolism. They contribute to adapt an individual to circumstances of life and illness. The unlimited supply of recombinant GH makes it possible to treat not only children with short stature but other disorders. In adults with GH deficiency, it has a marked effect on subjective well-being and body composition, and improves physical activity. GH may be promoted in new therapeutic areas such as severe hypercatabolic and denutrition states, dilated cardiomyopathy and several other more hypothetical areas. GH is not a wonder drug increasing physical performances in sport competitors or fighting against senescence. GH is a new therapeutic tool. Its efficacy must be evaluated through double-blind, placebo-controlled clinical trials. Currently, only benefits on psychological and physical symptoms of GH deficiency in adults have been validated.

Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

NASA Technical Reports Server (NTRS)

Swarthout, John T.; D'Alonzo, Richard C.; Selvamurugan, Nagarajan; Partridge, Nicola C.

2002-01-01

Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific

The Skeletal Muscle Anabolic Response to Plant- versus Animal-Based Protein Consumption.

PubMed

van Vliet, Stephan; Burd, Nicholas A; van Loon, Luc J C

2015-09-01

Clinical and consumer market interest is increasingly directed toward the use of plant-based proteins as dietary components aimed at preserving or increasing skeletal muscle mass. However, recent evidence suggests that the ingestion of the plant-based proteins in soy and wheat results in a lower muscle protein synthetic response when compared with several animal-based proteins. The possible lower anabolic properties of plant-based protein sources may be attributed to the lower digestibility of plant-based sources, in addition to greater splanchnic extraction and subsequent urea synthesis of plant protein-derived amino acids compared with animal-based proteins. The latter may be related to the relative lack of specific essential amino acids in plant- as opposed to animal-based proteins. Furthermore, most plant proteins have a relatively low leucine content, which may further reduce their anabolic properties when compared with animal proteins. However, few studies have actually assessed the postprandial muscle protein synthetic response to the ingestion of plant proteins, with soy and wheat protein being the primary sources studied. Despite the proposed lower anabolic properties of plant vs. animal proteins, various strategies may be applied to augment the anabolic properties of plant proteins. These may include the following: 1) fortification of plant-based protein sources with the amino acids methionine, lysine, and/or leucine; 2) selective breeding of plant sources to improve amino acid profiles; 3) consumption of greater amounts of plant-based protein sources; or 4) ingesting multiple protein sources to provide a more balanced amino acid profile. However, the efficacy of such dietary strategies on postprandial muscle protein synthesis remains to be studied. Future research comparing the anabolic properties of a variety of plant-based proteins should define the preferred protein sources to be used in nutritional interventions to support skeletal muscle mass gain

Anabolic Steroid Misuse Among US Adolescent Boys: Disparities by Sexual Orientation and Race/Ethnicity

PubMed Central

Calzo, Jerel P.; Griffiths, Scott; Murray, Stuart B.

2017-01-01

Objectives. To examine the prevalence of anabolic steroid misuse among US adolescent boys as a function of sexual orientation and race/ethnicity. Methods. We analyzed boys from the 2015 Youth Risk Behavior Survey (n = 6248; mean age = 16), a representative sample of US high school students. Lifetime prevalence of anabolic steroid misuse was dichotomized as never versus 1 or more times. Results. Sexual minority boys reported elevated misuse compared with heterosexual boys, within each level of race/ethnicity. Black, Hispanic, and White sexual minority boys reported misuse at approximately 25%, 20%, and 9%, respectively. Conclusions. Sexual orientation health disparities in anabolic steroid misuse disproportionally affect Black and Hispanic sexual minority adolescent boys, but more research is needed to understand the mechanisms driving these disparities. PMID:27997246

Anabolic agents: recent strategies for their detection and protection from inadvertent doping

PubMed Central

Geyer, Hans; Schänzer, Wilhelm; Thevis, Mario

2014-01-01

According to the World Anti-Doping Agency (WADA) Prohibited List, anabolic agents consist of exogenous anabolic androgenic steroids (AAS), endogenous AAS and other anabolic agents such as clenbuterol and selective androgen receptor modulators (SARMs). Currently employed strategies for their improved detection include the prolongation of the detection windows for exogenous AAS, non-targeted and indirect analytical approaches for the detection of modified steroids (designer steroids), the athlete’s biological passport and isotope ratio mass spectrometry for the detection of the misuse of endogenous AAS, as well as preventive doping research for the detection of SARMs. The recent use of these strategies led to 4–80-fold increases of adverse analytical findings for exogenous AAS, to the detection of the misuse of new designer steroids, to adverse analytical findings of different endogenous AAS and to the first adverse analytical findings of SARMs. The strategies of the antidoping research are not only focused on the development of methods to catch the cheating athlete but also to protect the clean athlete from inadvertent doping. Within the past few years several sources of inadvertent doping with anabolic agents have been identified. Among these are nutritional supplements adulterated with AAS, meat products contaminated with clenbuterol, mycotoxin (zearalenone) contamination leading to zeranol findings, and natural products containing endogenous AAS. The protection strategy consists of further investigations in case of reasonable suspicion of inadvertent doping, publication of the results, education of athletes and development of methods to differentiate between intentional and unintentional doping. PMID:24632537

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--anabolic implants and meat quality.

PubMed

Duckett, S K; Pratt, S L

2014-01-01

Anabolic implants are routinely used in the finishing phase of beef production to improve animal performance and feed efficiency. Implanting during the feedlot phase on average increases ADG 18%, feed intake 6%, feed efficiency 8%, carcass weight 5%, and ribeye area 4% compared with nonimplanted controls. Implants reduce the cost of beef production, which is important given current high feed costs and beef prices. In a 1996 review of 37 implant trials, the use of a combination (i.e., estrogenic and trenbolone acetate) implant increased returns by US$77/head compared with nonimplanted steers. If calculated using today's prices, a combination implant would increase returns by $163/head. However, concerns about potential negative effects of implants on marbling scores, quality grades, and tenderness exist. Changes in Warner-Bratzler shear force values of steaks from implanted steers are small (<0.5 kg) and appear related to an increase in initial tenderness, possibly due to hypertrophy of muscle fiber, instead of alterations in postmortem proteolysis. The increase in ribeye size observed with implanting may also reduce marbling scores through a dilution effect. The impact of anabolic implants on gene expression has shown that implanting downregulates expression of certain lipogenic genes (e.g., stearoyl-CoA desaturase, fatty acid synthetase, fatty acid elongase-6) in steers with low quality grades (Select-) but not in implanted steers with high quality grades (Choice-). Examination of the adipocyte's transcriptome has shown that 36 genes were differentially expressed due to implant treatment. More research is needed to further determine how anabolic implants alter lipogenic gene expression to address changes in marbling deposition with implant usage. Given our current high feed costs and cattle prices, anabolic implants are one of the most cost-effective technologies that can be used in beef production systems.

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Identification of black market products and potential doping agents in Germany 2010-2013.

PubMed

Krug, Oliver; Thomas, Andreas; Walpurgis, Katja; Piper, Thomas; Sigmund, Gerd; Schänzer, Wilhelm; Laussmann, Tim; Thevis, Mario

2014-11-01

The desire to increase the athletic performance, to 'optimize' an individual's appearance, and to complement but also to arguably substitute exercise by means of drugs and drug candidates has generated a considerable (illicit) market for compounds such as anabolic-androgenic steroids, stimulants, growth promoting peptide hormones, and so on. Genuinely developed for therapeutic use, their abuse/misuse generates enormous health risks, which has necessitated comprehensive controls of compound trafficking by customs and anti-doping authorities. From 2012 to 2013, the Bureau of Customs Investigation confiscated products containing anabolic-androgenic steroids (AAS; 259 kg), stimulants (13 kg), selective estrogen receptor modulators (SERMs; 24 kg), and human growth hormone (hGH; 3500 ampules). In cooperation with the Bureau and under the umbrella of the European Monitoring Center for Emerging Doping Agents (EuMoCEDA), the Cologne Anti-Doping Laboratory analyzed an additional 337 (black market) products between 2010 and 2013, allowing to monitor developments in drug use and, hence, the anticipation of new challenges in sports drug testing. Main tools utilized in characterizing confiscated materials were liquid chromatography-high resolution mass spectrometry (LC-HRMS), gas chromatography-high resolution mass spectrometry (GC-HRMS), and polyacrylamide gel electrophoresis (PAGE) with subsequent bottom-up identification of peptidic compounds using nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Among the 337 substances analyzed in the doping control laboratory in Cologne, 67 active ingredients were found, 49 of which being categorized as doping agents by the World Anti-Doping Agency (WADA). A total of 83.7 % accounted for steroidal substances (predominantly testosterone, trenbolone, and nandrolone and corresponding esters), 12.8 % accounted for peptide hormones and growth factors (predominantly hGH and growth hormone releasing peptides (GHRPs)), 3.2 % of

Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

NASA Technical Reports Server (NTRS)

Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Creson, Daniel L.; Sanford, Arthur P.; Wolf, Steven E.; Wolfe, Robert R.; Ferrando, Arny A.

2003-01-01

Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 microg. kg(-1). h(-1)) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 microg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol. kg(-1). min(-1)) of l-[ring-(2)H(5)]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 +/- 2.1 (C + AA) vs. 9.0 +/- 1.0 microg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

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…

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…

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)

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.

[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.

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

Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

PubMed Central

Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

2016-01-01

Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth.

PubMed

Brown, D M; Williams, H; Ryan, K J P; Wilson, T L; Daniel, Z C T R; Mareko, M H D; Emes, R D; Harris, D W; Jones, S; Wattis, J A D; Dryden, I L; Hodgman, T C; Brameld, J M; Parr, T

2016-06-28

We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth.

Nutrient timing revisited: is there a post-exercise anabolic window?

PubMed Central

2013-01-01

Nutrient timing is a popular nutritional strategy that involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. Some have claimed that this approach can produce dramatic improvements in body composition. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients. The post-exercise period is widely considered the most critical part of nutrient timing. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an anabolic “window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations. However, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with respect to anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise. PMID:23360586

Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

PubMed

Hansma, Patrick; Diaz, Francisco J; Njiwaji, Chantel

2016-03-01

Liver cysts are commonly found incidentally from imaging scans or at autopsy. These benign neoplasms vary in size and represent a heterogeneous group of disorders, for which the demographics, risk factors, apparent inciting event, clinical presentation, and outcome are varied. Complications that can develop from a liver cyst include development of spontaneous hemorrhage, infection, and/or obstruction. Although the etiology of liver cysts varies, fatal rupture of a hemorrhagic liver cyst due to anabolic steroid use is a rare occurrence. In fact, there are few reported cases in journal literature. We report a case of a fatal liver cyst rupture with resultant hemoperitoneum in the presence of anabolic steroid (stanozolol) use.

Hormones and the blood-brain barrier.

PubMed

Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

2015-03-01

Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis.

PubMed

Deshpande, Sagar S; Gallagher, Katherine K; Donneys, Alexis; Tchanque-Fossuo, Catherine N; Sarhaddi, Deniz; Nelson, Noah S; Chepeha, Douglas B; Buchman, Steven R

2013-07-01

Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 µg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. Parathyroid hormone-treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration-approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.

Metabolism and catabolism in hip fracture patients: nutritional and anabolic intervention--a review.

PubMed

Hedström, Margareta; Ljungqvist, Olle; Cederholm, Tommy

2006-10-01

Patients suffering from hip fracture are known to be at risk of catabolism and protein-energy malnutrition. In this review we discuss the pathogenesis of hip fracture-related catabolism per- and postoperatively. We also describe the consequences of malnutrition after a hip fracture and summarize studies that have evaluated the effect of nutritional or anabolic treatment of these patients. There has been relatively little published on the effects of nutritional and anabolic pharmacological interventions for improvement of nutritional status and on the role of nutritional status in clinical outcomes. Even so, there have been 19 randomized studies in this field. 12 studies evaluated nutritional supplementation or protein supplementation. 6 found improved clinical outcome with fewer complications, faster recovery and shorter length of hospital stay, whereas the others reported no difference in clinical outcome. For pharmacological interventions, the outcomes have been even less clear. Supplementation studies in general appear to be underpowered or suffer logistic problems. Studies of higher scientific quality are needed, and enteral feeding, anabolic treatment and multimodal approaches need to be evaluated in greater depth.

Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

PubMed

Laron, Z

2001-01-01

The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.

PubMed

Rosen, J; Negro-Vilar, A

2002-03-01

hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement.

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

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.

Coronary calcification in body builders using anabolic steroids.

PubMed

Santora, Lawrence J; Marin, Jairo; Vangrow, Jack; Minegar, Craig; Robinson, Mary; Mora, Janet; Friede, Gerald

2006-01-01

The authors measured coronary artery calcification as a means of examining the impact of anabolic steroids on the development of atherosclerotic disease in body builders using anabolic steroids over an extended period of time. Fourteen male professional body builders with no history of cardiovascular disease were evaluated for coronary artery calcium, serum lipids, left ventricular function, and exercise-induced myocardial ischemia. Seven subjects had coronary artery calcium, with a much higher than expected mean score of 98. Six of the 7 calcium scores were >90th percentile. Mean total cholesterol was 192 mg/dL, while mean high-density lipoprotein was 23 mg/dL and the mean ratio of total cholesterol to high-density lipoprotein was 8.3. Left ventricular ejection fraction ranged between 49% and 68%, with a mean of 59%. No subject had evidence of myocardial ischemia. This small group of professional body builders with a long history of steroid abuse had high levels of coronary artery calcium for age. The authors conclude that in this small pilot study there is an association between early coronary artery calcium and long-term steroid abuse. Large-scale studies are warranted to further explore this association.

Anabolic Androgenic Steroid (AAS) Related Deaths: Autoptic, Histopathological and Toxicological Findings

PubMed Central

Frati, Paola; Busardò, Francesco P.; Cipolloni, Luigi; Dominicis, Enrico De; Fineschi, Vittorio

2015-01-01

Anabolic androgenic steroids (AASs) represent a large group of synthetic derivatives of testosterone, produced to maximize anabolic effects and minimize the androgenic ones. AAS can be administered orally, parenterally by intramuscular injection and transdermally. Androgens act by binding to the nuclear androgen receptor (AR) in the cytoplasm and then translocate into the nucleus. This binding results in sequential conformational changes of the receptor affecting the interaction between receptor and protein, and receptor and DNA. Skeletal muscle can be considered as the main target tissue for the anabolic effects of AAS, which are mediated by ARs which after exposure to AASs are up-regulated and their number increases with body building. Therefore, AASs determine an increase in muscle size as a consequence of a dose-dependent hypertrophy resulting in an increase of the cross-sectional areas of both type I and type II muscle fibers and myonuclear domains. Moreover, it has been reported that AASs can increase tolerance to exercise by making the muscles more capable to overload therefore shielding them from muscle fiber damage and improving the level of protein synthesis during recovery. Despite some therapeutic use of AASs, there is also wide abuse among athletes especially bodybuilders in order to improve their performances and to increase muscle growth and lean body mass, taking into account the significant anabolic effects of these drugs. The prolonged misuse and abuse of AASs can determine several adverse effects, some of which may be even fatal especially on the cardiovascular system because they may increase the risk of sudden cardiac death (SCD), myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy. The aim of this review is to focus on deaths related to AAS abuse, trying to evaluate the autoptic, histopathological and toxicological findings in order to investigate the pathophysiological mechanism that underlines this type of death, which

Anabolic-Androgenic Steroid Use Among 1,010 College Men.

ERIC Educational Resources Information Center

Pope, Harrison G., Jr.; And Others

1988-01-01

Two percent of 1,010 male college students responding to a questionnaire about anabolic-androgenic steroid use reported using steroids; most of the users were competitive athletes, although some used steroids to improve their physical appearance. Users were not distinguished from non-users in terms of academic achievement or use of other illicit…

Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]-acetic acid compounds as potent, selective, thyroid hormone receptor β agonists.

PubMed

Burkholder, Timothy P; Cunningham, Brian E; Clayton, Joshua R; Lander, Peter A; Brown, Matthew L; Doti, Robert A; Durst, Gregory L; Montrose-Rafizadeh, Chahrzad; King, Constance; Osborne, Harold E; Amos, Robert M; Zink, Richard W; Stramm, Lawrence E; Burris, Thomas P; Cardona, Guemalli; Konkol, Debra L; Reidy, Charles; Christe, Michael E; Genin, Michael J

2015-04-01

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor β (TRβ) agonists is described. Compounds with >50× binding selectivity for TRβ over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity.

PubMed

Intini, Giuseppe; Nyman, Jeffry S

2015-06-01

Bone fractures remain a serious health burden and prevention and enhanced healing of fractures have been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1(+/-)) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2(c/c);Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1(+/-) mice were crossed with Bmp2(c/c);Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity

PubMed Central

Intini, Giuseppe; Nyman, Jeffry S.

2015-01-01

Bone fractures remain a serious health burden and prevention and enhanced healing of fractures has been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1+/−) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2c/c;Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1+/− mice were crossed with Bmp2c/c;Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy. PMID:25603465

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.

Chromosome damage and cytotoxicity in oral mucosa cells after 2 months of exposure to anabolic steroids (decadurabolin and winstrol) in weight lifting.

PubMed

Martins, Renato A; Gomes, Guilherme A S; Aguiar, Odair; Medalha, Carla C; Ribeiro, Daniel A

2010-12-01

The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells from anabolic steroid users after 2 months of exposure. Two experimental groups consisting of 15 adult males who practise weight lifting and are anabolic steroid users or 15 adult males who practise weight lifting, but are non-anabolic steroid users, were recruited. In addition, 20 sedentary males, who do not practise any physical activity regularly, were matched by age with experimental groups. No significant statistical differences (p>0.05) were noticed in individuals who practise physical activity only. On the other hand, an increase of micronucleated cells (MNCs) in anabolic steroid (decadurabulin and Winstrol) users was observed. Regarding cytotoxic parameters, the same observation has occurred, that is, significant statistical differences (p<0.05) were noticed in the group exposed to anabolic steroids when compared with other controls, as depicted by high frequencies of pyknosis, karyolysis and karyorrhexis. Taken together, our results suggest that genomic instability and cytotoxicity are induced by anabolic steroid administration in oral mucosa cells as assessed by the micronucleus test. Copyright 2010 Elsevier Inc. All rights reserved.

Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone

PubMed Central

Tu, Xiaolin; Delgado-Calle, Jesus; Condon, Keith W.; Maycas, Marta; Zhang, Huajia; Carlesso, Nadia; Taketo, Makoto M.; Burr, David B.; Plotkin, Lilian I.; Bellido, Teresita

2015-01-01

Osteocytes, >90% of the cells in bone, lie embedded within the mineralized matrix and coordinate osteoclast and osteoblast activity on bone surfaces by mechanisms still unclear. Bone anabolic stimuli activate Wnt signaling, and human mutations of components along this pathway underscore its crucial role in bone accrual and maintenance. However, the cell responsible for orchestrating Wnt anabolic actions has remained elusive. We show herein that activation of canonical Wnt signaling exclusively in osteocytes [dominant active (da)βcatOt mice] induces bone anabolism and triggers Notch signaling without affecting survival. These features contrast with those of mice expressing the same daß-catenin in osteoblasts, which exhibit decreased resorption and perinatal death from leukemia. daßcatOt mice exhibit increased bone mineral density in the axial and appendicular skeleton, and marked increase in bone volume in cancellous/trabecular and cortical compartments compared with littermate controls. daßcatOt mice display increased resorption and formation markers, high number of osteoclasts and osteoblasts in cancellous and cortical bone, increased bone matrix production, and markedly elevated periosteal bone formation rate. Wnt and Notch signaling target genes, osteoblast and osteocyte markers, and proosteoclastogenic and antiosteoclastogenic cytokines are elevated in bones of daßcatOt mice. Further, the increase in RANKL depends on Sost/sclerostin. Thus, activation of osteocytic β-catenin signaling increases both osteoclasts and osteoblasts, leading to bone gain, and is sufficient to activate the Notch pathway. These findings demonstrate disparate outcomes of β-catenin activation in osteocytes versus osteoblasts and identify osteocytes as central target cells of the anabolic actions of canonical Wnt/β-catenin signaling in bone. PMID:25605937

Acute unilateral sensorineural hearing loss associated with anabolic steroids and polycythaemia: case report.

PubMed

Tikka, T; Mistry, N; Janjua, A

2016-03-01

Unilateral sudden sensorineural hearing loss due to an infarct in the vertebrobasilar system has been widely reported. Most patients have a background of traditional coronary risk factors related to these cerebrovascular episodes. A 32-year-old male, a regular user of anabolic steroids, presented to the emergency department with unilateral sensorineural hearing loss and symptoms suggestive of an infarct of the anterior inferior cerebellar artery but in the absence of risk factors for ischaemic stroke. Magnetic resonance imaging confirmed the presence of infarction in the region supplied by the anterior inferior cerebellar artery. Polycythaemia was found on haematological analysis, which we believe was secondary to the use of anabolic steroids. The patient was commenced on aspirin as per the stroke management protocol. There was resolution of neurological symptomatology six weeks after the episode, but no improvement in hearing. To our knowledge, this is the first case report of unilateral sensorineural hearing loss secondary to the use of anabolic steroids causing polycythaemia. This cause should be considered in the differential diagnosis of patients presenting with sensorineural hearing loss, especially in young males, when no other risk factors can be identified.

Growth Hormone Resistance—Special Focus on Inflammatory Bowel Disease

PubMed Central

Soendergaard, Christoffer; Young, Jonathan A.; Kopchick, John J.

2017-01-01

Growth hormone (GH) plays major anabolic and catabolic roles in the body and is important for regulating several aspects of growth. During an inflammatory process, cells may develop a state of GH resistance during which their response to GH stimulation is limited. In this review, we will emphasize specific mechanisms governing the formation of GH resistance in the active phase of inflammatory bowel disease. The specific molecular effects mediated through individual inflammatory mediators and processes will be highlighted to provide an overview of the transcriptional, translational and post-translational inflammation-mediated impacts on the GH receptor (GHR) along with the impacts on GH-induced intracellular signaling. We also will review GH’s effects on mucosal healing and immune cells in the context of experimental colitis, human inflammatory bowel disease and in patients with short bowel syndrome. PMID:28486400

Gastroenteropancreatic hormones and metabolism in fish.

PubMed

Nelson, Laura E; Sheridan, Mark A

2006-09-01

Metabolism of vertebrates integrates a vast array of systems and processes, including the pursuit and capture of food, feeding and digestion of ingested food, absorption and transport of nutrients, assimilation, partitioning and utilization of energy, and the processing and elimination of wastes. Fish, which are the most diverse group of vertebrates and occupy a wide range of habitats and display numerous life history patterns, have proven to be important models for the study of the structure, biosynthesis, evolution, and function of gastroenteropancreatic (GEP) hormones. Food intake is promoted by galanin, neuropeptide Y, and pancreatic polypeptide (PP), while cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) inhibit food intake. Digestion of ingested food is facilitated by CCK, PP, and secretin by coordinating gastrointestinal tract motility and regulation of exocrine secretion. Somatostatins (SS), on the other hand, generally inhibit exocrine secretions. Insulin facilitates assimilation by promoting the uptake of nutrient molecules (e.g., glucose, amino acids, and fatty acids) into cells. Insulin also is generally anabolic and stimulates the synthesis and deposition of energy reserves (e.g., glycogen, triacylglycerol) as well as of proteins, thereby facilitating organismal growth. Insulin-like growth factors (e.g., IGF-1) also promote cell proliferation and organismal growth. Breakdown and mobilization of stored energy reserves is stimulated by glucagon, GLP-1, and SS. Somatostatins also affect metabolism and reproduction via their effects on the thyroid axis as well as growth via effects on growth hormone (GH) release and perhaps directly via modulation of GH sensitivity. Studies in fish have revealed that GEP hormones play an important role in coordinating the various aspects of metabolism with each other and with the physiological and developmental status of the animal as well as with the environment.

Exposure to media predicts use of dietary supplements and anabolic-androgenic steroids among Flemish adolescent boys.

PubMed

Frison, Eline; Vandenbosch, Laura; Eggermont, Steven

2013-10-01

This study examined whether different types of media affect the use of dietary proteins and amino acid supplements, and intent to use anabolic-androgenic steroids. A random sample of 618 boys aged 11-18 years from eight schools in the Flemish part of Belgium completed standardized questionnaires as part of the Media and Adolescent Health Study. The survey measured exposure to sports media, appearance-focused media, fitness media, use of dietary supplements, and intent to use anabolic-androgenic steroids. Data were analyzed using logistic regressions and are presented as adjusted odds ratios (OR) and 95 % confidence intervals (CI); 8.6 % indicated to have used dietary proteins, 3.9 % indicated to have used amino acid supplements, and 11.8 % would consider using anabolic-androgenic steroids. After adjusting for fitness activity, exposure to fitness media was associated with the use of dietary proteins (OR = 7.24, CI = 2.25-23.28) and amino acid supplements (5.16, 1.21-21.92; 44.30, 8.25-238). Intent to use anabolic-androgenic steroids was associated with exposure to fitness media (2.38, 1.08-5.26; 8.07, 2.55-25.53) and appearance-focused media (6.02, 1.40-25.82; 8.94, 1.78-44.98). Sports media did not correlate with the use of dietary supplements and intent to use anabolic-androgenic steroids. Specific types of media are strong predictors of the use of supplements in adolescent boys. This provides an opportunity for intervention and prevention through the selection of fitness media as a communication channel. Health practitioners should also be aware that the contemporary body culture exerts pressure not only on girls but also on boys.

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)

PYOMYOSITIS IN ATHLETES AFTER THE USE OF ANABOLIC STEROIDS - CASE REPORTS.

PubMed

Filho, Nivaldo Souza Cardozo; Gaspar, Eric Figueirido; Siqueira, Karina Levy; Monteiro, Gustavo Cará; Andreoli, Carlos Vicente; Ejnisman, Benno; Cohen, Moisés

2011-01-01

To report on the management of five cases of pyomyositis in athletes after the use of anabolic steroids. Over the past 10 years, five cases of athletes who developed pyomyositis after using anabolic steroids were attended at the Sports Trauma Center (CETE), EPM-UNIFESP. All the patients were diagnosed clinically and through laboratory and imaging tests. Surgical treatment was carried out (with collection of material for culturing) and antibiotic therapy was administered. In four cases, the injection sites were in the upper limbs and in one case, in the gluteus muscles bilaterally as well as in the upper limbs. In all five cases, occurrences of leukocytosis and neutrophilia were observed in the hemogram. After debridement, the germs of normal skin (S. aureus and S. viridans) were found in cultures on the secretions. Demarcation of the abscess and examination of the muscle plane in which the abscess was located were performed using ultrasound and magnetic resonance imaging. All the patients responded to broad-spectrum antibiotic therapy. Two cases required more than one surgical procedure because of the appearance of more than one abscess site with different evolution times. The use of anabolic steroids by some athletes may have grave consequences. Rapid, energetic and multidisciplinary intervention is necessary in such cases in order to avoid undesirable results. The right treatment healed the athletes completely, and they returned to their sports at the same level.

PYOMYOSITIS IN ATHLETES AFTER THE USE OF ANABOLIC STEROIDS - CASE REPORTS

PubMed Central

Filho, Nivaldo Souza Cardozo; Gaspar, Eric Figueirido; Siqueira, Karina Levy; Monteiro, Gustavo Cará; Andreoli, Carlos Vicente; Ejnisman, Benno; Cohen, Moisés

2015-01-01

Objective: To report on the management of five cases of pyomyositis in athletes after the use of anabolic steroids. Method: Over the past 10 years, five cases of athletes who developed pyomyositis after using anabolic steroids were attended at the Sports Trauma Center (CETE), EPM-UNIFESP. Results: All the patients were diagnosed clinically and through laboratory and imaging tests. Surgical treatment was carried out (with collection of material for culturing) and antibiotic therapy was administered. In four cases, the injection sites were in the upper limbs and in one case, in the gluteus muscles bilaterally as well as in the upper limbs. In all five cases, occurrences of leukocytosis and neutrophilia were observed in the hemogram. After debridement, the germs of normal skin (S. aureus and S. viridans) were found in cultures on the secretions. Demarcation of the abscess and examination of the muscle plane in which the abscess was located were performed using ultrasound and magnetic resonance imaging. All the patients responded to broad-spectrum antibiotic therapy. Two cases required more than one surgical procedure because of the appearance of more than one abscess site with different evolution times. Conclusion: The use of anabolic steroids by some athletes may have grave consequences. Rapid, energetic and multidisciplinary intervention is necessary in such cases in order to avoid undesirable results. The right treatment healed the athletes completely, and they returned to their sports at the same level. PMID:27026995

Integrated analytical approach in veal calves administered the anabolic androgenic steroids boldenone and boldione: urine and plasma kinetic profile and changes in plasma protein expression.

PubMed

Draisci, Rosa; Montesissa, Clara; Santamaria, Barbara; D'Ambrosio, Chiara; Ferretti, Giovanni; Merlanti, Roberta; Ferranti, Carolina; De Liguoro, Marco; Cartoni, Claudia; Pistarino, Erika; Ferrara, Lino; Tiso, Micaela; Scaloni, Andrea; Cosulich, M Elisabetta

2007-09-01

Surveillance of illegal use of steroids hormones in cattle breeding is a key issue to preserve human health. To this purpose, an integrated approach has been developed for the analysis of plasma and urine from calves treated orally with a single dose of a combination of the androgenic steroids boldenone and boldione. A quantitative estimation of steroid hormones was obtained by LC-APCI-Q-MS/MS analysis of plasma and urine samples obtained at various times up to 36 and 24 h after treatment, respectively. These experiments demonstrated that boldione was never found, while boldenone alpha- and beta-epimers were detected in plasma and urine only within 2 and 24 h after drug administration, respectively. Parallel proteomic analysis of plasma samples was obtained by combined 2-DE, MALDI-TOF-MS and muLC-ESI-IT-MS/MS procedures. A specific protein, poorly represented in normal plasma samples collected before treatment, was found upregulated even 36 h after hormone treatment. Extensive mass mapping experiments proved this component as an N-terminal truncated form of apolipoprotein A1 (ApoA1), a protein involved in cholesterol transport. The expression profile of ApoA1 analysed by Western blot analysis confirmed a significant and time dependent increase of this ApoA1 fragment. Then, provided that further experiments performed with a growth-promoting schedule will confirm these preliminary findings, truncated ApoA1 may be proposed as a candidate biomarker for steroid boldenone and possibly other anabolic androgens misuse in cattle veal calves, when no traces of hormones are detectable in plasma or urine.

Commentary: Synthetic Anabolic-Androgenic Steroids: A Plea for Controlled Substance Status.

ERIC Educational Resources Information Center

Taylor, William N.

1987-01-01

The widespread abuse of synthetic anabolic-androgenic steriods, their habit-forming properties, and their other adverse effects are good reasons for reclassification of steriods as controlled substances under federal law, a step which may combat their abuse. (Author/CB)

Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

PubMed

Lang, Charles H; Frost, Robert A

2002-05-01

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

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

Frequency of Anabolic Steroids Abuse in Bodybuilder Athletes in Kerman City†This article has been published in the Journal of Rafsanjan University of Medical Sciences in Persian language.

PubMed Central

Sepehri, Gholamreza; Mousavi Fard, Majid; Sepehri, Ehsan

2009-01-01

Background: Athletes, especially bodybuilders, abuse anabolic steroid drugs to improve their strength and enhance their muscle growth and appearance. This study was conducted to determine the type and frequency of anabolic steroids abuse in bodybuilder athletes in Kerman City. Methods: A confidential questionnaire which included demographic data (age, education), name of abused anabolic drug and duration of drug abuse was completed by 202 bodybuilder athletes, and the collected data were analyzed using Chi Square test. A value of p < 0.05 was considered significant. Findings: The frequency of anabolic steroid abuse was 18.8%. The mean period of bodybuilding activity was significantly higher in those used the anabolic drugs (38.8 months), comparing to those did not use any drugs (14.3 months). Oxymetholone was the most common drug used by athletes (42% merely used Oxymetholone). The frequency of anabolic steroids abuse was not related to education and age of the bodybuilder athletes. Conclusion: Bodybuilder athletes in Kerman city abuse anabolic steroids, and the health care system should plan to inform them about anabolic steroid adverse effects. PMID:24494079

Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.

PubMed

Davis, D L; Telang, N T; Osborne, M P; Bradlow, H L

1997-04-01

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.

Synthesis and chemical reactions of the steroidal hormone 17α-methyltestosterone.

PubMed

El-Desoky, El-Sayed Ibrahim; Reyad, Mahmoud; Afsah, Elsayed Mohammed; Dawidar, Abdel-Aziz Mahmoud

2016-01-01

Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry of the steroidal hormone 17α-methyltestosterone that is approved by Food and Drug Administration (FDA) in the United States as an androgen for estrogen-androgen hormone replacement therapy treatment. The analog also offers special possibilities for the prevention/treatment of hormone-sensitive cancers. The testosterone skeleton has important functionalities in the molecule that can act as a carbonyl component, an active methylene compound, α,β-unsaturated enone and tertiary hydroxyl group in various chemical reactions to access stereoisomeric steroidal compounds with potent activity. In addition, microbiological methods of synthesis and transformation of this hormone are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis.

PubMed

Nahon, Jean-Louis

2006-08-01

A number of different neuropeptides exert powerful concerted controls on feeding behavior and energy balance, most of them being produced in hypothalamic neuronal networks under stimulation by anabolic and catabolic peripheral hormones such as ghrelin and leptin, respectively. These peptide-expressing neurons interconnect extensively to integrate the multiple opposing signals that mediate changes in energy expenditure. In the present review I have summarized our current knowledge about two key peptidic systems involved in regulating appetite and energy homeostasis, the melanocortin system (alpha-MSH, agouti and Agouti-related peptides, MC receptors and mahogany protein) and the melanin-concentrating hormone system (proMCH-derived peptides and MCH receptors) that contribute to satiety and feeding-initiation, respectively, with concurrent effects on energy expenditure. I have focused particularly on recent data concerning transgenic mice and the ongoing development of MC/MCH receptor antagonists/agonists that may represent promising drugs to treat human eating disorders on both sides of the energy balance (anorexia, obesity).

Effect of carbohydrate-electrolyte consumption on insulin, cortisol hormones and blood glucose after high-intensity exercise.

PubMed

Mor, Ahmet; Kayacan, Yildirim; Ipekoglu, Gokhan; Arslanoglu, Erkal

2018-04-21

This study aimed to examine the effect of CHO-E consumption after high-intensity exercise on insulin, cortisol hormones and blood glucose responses, which is important for performance and recovery in athletes. Sixteen volunteers, male athletes, participated into this study. Athletes were divided into two groups as experiment (CHO-E) and placebo (PLA). Blood was taken from the athletes three times as basal, post-exercise (PE) and 2 h after ingestion of supplement (PS). When inter-group comparisons, insulin was significantly higher in the CHO-E group than the PLA group at the PS phase (p < .05). Cortisol significantly decreased in the CHO-E group at the PS compared to the PE (p < .05). Carbohydrate-electrolyte consumption after high-intensity exercise, accelerates the recovery process by providing optimal recovery, and enable the metabolism to remain in the anabolic state by preventing it from entering in the catabolic process as well as provides hormonal balance in metabolism.

[Ingestion of anabolic steroids and ischaemic stroke. A clinical case report and review of the literature].

PubMed

García-Esperón, Carlos; Hervás-García, José Vicente; Jiménez-González, Marta; Pérez de la Ossa-Herrero, Natalia; Gomis-Cortina, Meritxell; Dorado-Bouix, Laura; López-Cancio Martinez, Elena; Castaño-Duque, Carlos H; Millán-Torné, Mónica; Dávalos, Antonio

2013-03-16

INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.

US Army Institute of Surgical Research Annual Research Progress Report for Fiscal Year 1988

DTIC Science & Technology

1988-10-01

promote anabolism in surgical patients. Patients (n=9) received a constant parenteral infusion of a hypocaloric diet which provided 1100 kcal/24 h...Protropin ) in calorie-deprived human volunteers illustrated its anabolic effect. Hypocaloric parenteral nutrition resulted in negative balance of nitrogen...human growth hormone. Lancet I(7062):7-12, 1959. 5. Manson JM and Wilmore DW: Positive nitrogen balance with human growth hormone and hypocaloric

 Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

PubMed

Díaz, Francia C; Sáez-González, Esteban; Benlloch, Salvador; Álvarez-Sotomayor, Diego; Conde, Isabel; Polo, Begoña; García, María; Rodríguez, María; Prieto, Martín

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

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

Effects of anabolic-androgens on brain reward function.

PubMed

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.

The Buzz About Anabolic Androgenic Steroids: Electrophysiological Effects in Excitable Tissues

PubMed Central

Oberlander, Joseph G.; Penatti, Carlos A. A.; Porter, Donna M.; Henderson, Leslie P.

2012-01-01

Anabolic androgenic steroids (AAS) comprise a large and growing class of synthetic androgens used clinically to promote tissue-building in individuals suffering from genetic disorders, injuries and diseases. Despite these beneficial therapeutic applications, the predominant use of AAS is illicit: these steroids are self-administered to promote athletic performance and body image. Hand in hand with the desired anabolic actions of the AAS are untoward effects on the brain and behavior. While the signaling routes by which the AAS impose both beneficial and harmful actions may be quite diverse, key endpoints are likely to include ligand-gated and voltage-dependent ion channels that govern the activity of electrically excitable tissues. Here we review the known effects of AAS on molecular targets that play critical roles in controlling electrical activity, with a specific focus on the effects of AAS on neurotransmission mediated by GABAA receptors in the central nervous system (CNS). PMID:22576754

The Buzz about anabolic androgenic steroids: electrophysiological effects in excitable tissues.

PubMed

Oberlander, Joseph G; Penatti, Carlos A A; Porter, Donna M; Henderson, Leslie P

2012-01-01

Anabolic androgenic steroids (AAS) comprise a large and growing class of synthetic androgens used clinically to promote tissue-building in individuals suffering from genetic disorders, injuries, and diseases. Despite these beneficial therapeutic applications, the predominant use of AAS is illicit: these steroids are self-administered to promote athletic performance and body image. Hand in hand with the desired anabolic actions of the AAS are untoward effects on the brain and behavior. While the signaling routes by which the AAS impose both beneficial and harmful actions may be quite diverse, key endpoints are likely to include ligand-gated and voltage-dependent ion channels that govern the activity of electrically excitable tissues. Here, we review the known effects of AAS on molecular targets that play critical roles in controlling electrical activity, with a specific focus on the effects of AAS on neurotransmission mediated by GABA(A) receptors in the central nervous system. Copyright © 2012 S. Karger AG, Basel.

Parathyroid Hormone Therapy Mollifies Radiation-Induced Biomechanical Degradation in Murine Distraction Osteogenesis

PubMed Central

Deshpande, Sagar S.; Gallagher, Katherine K.; Donneys, Alexis; Tchanque-Fossuo, Catherine N.; Sarhaddi, Deniz; Nelson, Noah S.; Chepeha, Douglas B.; Buchman, Steven R.

2015-01-01

Objective Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Methods Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 μg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. Results Parathyroid hormone–treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. Conclusions The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration–approved drug on formulary, significantly improve outcomes in a model of

Systemic and splanchnic metabolic response to exogenous human growth hormone.

PubMed

Dahn, M S; Lange, M P

1998-05-01

Evidence exists indicating that growth hormone (GH) resistance in some disease states such as hypercatabolic conditions may limit the metabolic benefit associated with recombinant human growth hormone (rhGH) administration. It was the purpose of this study to compare the systemic and splanchnic effects of rhGH in patients with sepsis exhibiting systemic inflammatory response syndrome (SIRS) with the response observed in normal volunteers. Because insulin-like growth factor I (IGF-I) is believed to be the dominant factor responsible for the anabolic effects of rhGH, particular attention was given to this secondary effector. The systemic and splanchnic effects of rhGH (0.15 mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I, urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and splanchnic oxygen exchange were measured after a 48-hour course of rhGH. Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF-I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and Sepsis/SIRS + Nutrition groups, respectively, compared with normal control subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined by a similar magnitude in all three groups. Hepatic blood flow remained unaffected, but rhGH administration increased splanchnic oxygen consumption in all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p < 0.05 relative to corresponding basal) resulting in a decline of basal to end therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%; Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55% +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that

Pressor mechanism evaluation for phytochemical compounds using in silico compound-protein interaction prediction.

PubMed

He, Min; Cao, Dong-Sheng; Liang, Yi-Zeng; Li, Ya-Ping; Liu, Ping-Le; Xu, Qing-Song; Huang, Ren-Bin

2013-10-01

In this study, a method was applied to evaluate pressor mechanisms through compound-protein interactions. Our method assumed that the compounds with different pressor mechanisms should bind to different target proteins, and thereby these mechanisms could be differentiated using compound-protein interactions. Twenty-six phytochemical components and 46 tested target proteins related to blood pressure (BP) elevation were collected. Then, in silico compound-protein interactions prediction probabilities were calculated using a random forest model, which have been implemented in a web server, and the credibility was judged using related literature and other methods. Further, a heat map was constructed, it clearly showed different prediction probabilities accompanied with hierarchical clustering analysis results. Followed by a compound-protein interaction network was depicted according to the results, we can see the connectivity layout of phytochemical components with different target proteins within the BP elevation network, which guided the hypothesis generation of poly-pharmacology. Lastly, principal components analysis (PCA) was carried out upon the prediction probabilities, and pressor targets could be divided into three large classes: neurotransmitter receptors, hormones receptors and monoamine oxidases. In addition, steroid glycosides seem to be close to the region of hormone receptors, and a weak difference existed between them. This work explored the possibility for pharmacological or toxicological mechanism classification using compound-protein interactions. Such approaches could also be used to deduce pharmacological or toxicological mechanisms for uncharacterized compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist.

PubMed

Kim, Seon-Mi; Lee, Minhee; Lee, So Young; Park, Euisun; Lee, Soo-Min; Kim, Eun Jeong; Han, Min Young; Yoo, Taekyung; Ann, Jihyae; Yoon, Suyoung; Lee, Jiyoun; Lee, Jeewoo

2016-10-13

We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound. Considering that 18a exhibited highly potent and selective antagonistic activity toward the hGnRHRs along with favorable pharmacokinetic profiles, we believe that 18a may represent a promising candidate for an orally available hormonal therapy.

Effects of Anabolic Steroids on Lipoprotein Profiles of Female Weight Lifters.

ERIC Educational Resources Information Center

Moffatt, Robert J.; And Others

1990-01-01

This study examined the effects of resistance exercise and anabolic steroids on lipoprotein profiles of female weightlifters. The study found that women who participate in resistance training have better lipoprotein profiles than their sedentary counterparts, but these changes do not offset the deleterious effects of steroid use. (SM)

Assessment of Bone Quality in Osteoporosis Treatment with Bone Anabolic Agents: Really Something New?

PubMed

Ulivieri, Fabio M; Caudarella, Renata; Camisasca, Marzia; Cabrini, Daniela M; Merli, Ilaria; Messina, Carmelo; Piodi, Luca P

2018-04-20

Osteoporosis is a chronic pathologic condition, particularly of the elderly, in which a reduction of bone mineral density (BMD) weakens bone, leading to the so-called fragility fractures, most often of spine and femur. The gold standard exam for the quantitative measurement of BMD is the dual X-ray photon absorptiometry (DXA), a radiological method. However, a relevant number of fragility fractures occurs in the range of normal BMD values, meaning that also qualitative aspects of bone play a role, namely bone architecture and bone geometry. Bone structure is investigated by microCT and histomorphometry, which necessitate an invasive approach with a biopsy, usually taken at the iliac crest, not the typical site of fragility fractures. New tools, trabecular bone score (TBS) and hip structural analysis (HSA), obtained during DXA, can supply informations about bone structure of spine and femur, respectively, in a not invasive way. Therapy of osteoporosis is based on two types of drugs leading to an increase of BMD: antiresorptive and anabolic treatments. The antiresorptive drugs inhibit the osteoclasts, whereas teriparatide and, in part, strontium ranelate ameliorate bone structure. The present review deals with the relation between the anabolic drugs for osteoporosis and the cited new tools which investigate bone architecture and geometry, in order to clarify if they represent a real advantage in monitoring efficacy of osteoporosis' treatment. Data from the studies show that increases of TBS and HSA values after anabolic therapy are small and very close to their least significant change at the end of the usual period of treatment. Therefore, it is questionable if TBS and HSA are really helpful in monitoring bone quality and in defining reduction of individual fragility fracture risk during osteoporosis treatment with bone anabolic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anabolic-androgenic steroid use and involvement in violent behavior in a nationally representative sample of young adult males in the United States.

PubMed

Beaver, Kevin M; Vaughn, Michael G; Delisi, Matt; Wright, John Paul

2008-12-01

We examined the effects of anabolic-androgenic steroid use on serious violent behavior. Multivariate models based on data from the National Longitudinal Study of Adolescent Health (N = 6823) were used to examine the association between lifetime and past-year self-reported anabolic-androgenic steroid use and involvement in violent acts. Compared with individuals who did not use steroids, young adult males who used anabolic-androgenic steroids reported greater involvement in violent behaviors after we controlled for the effects of key demographic variables, previous violent behavior, and polydrug use.

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

PubMed Central

Lahiri, Debomoy K.; Sokol, Deborah K.; Erickson, Craig; Ray, Balmiki; Ho, Chang Y.; Maloney, Bryan

2013-01-01

Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secreted APP α, is elevated in persons with autism. This has led to the “anabolic hypothesis” of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein, Ras small GTPase/extracellular signal-regulated kinase, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin. We also present additional evidence of magnetic resonance imaging intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP’s involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP’s contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence. PMID:23801940

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men

PubMed Central

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Meschi, Tiziana; Ticinesi, Andrea; Dominguez, Ligia J.; Barbagallo, Mario; Dall'Aglio, Elisabetta; Ceda, Gian Paolo

2014-01-01

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly. PMID:24723948

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men.

PubMed

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Nouvenne, Antonio; Meschi, Tiziana; Ticinesi, Andrea; Dominguez, Ligia J; Barbagallo, Mario; Dall'aglio, Elisabetta; Ceda, Gian Paolo

2014-01-01

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly.

The Anabolic 500 survey: characteristics of male users versus nonusers of anabolic-androgenic steroids for strength training.

PubMed

Ip, Eric J; Barnett, Mitchell J; Tenerowicz, Michael J; Perry, Paul J

2011-08-01

To contrast the characteristics of two groups of men who participated in strength-training exercise-those who reported anabolicandrogenic steroid (AAS) use versus those who reported no AAS use. Analysis of data from the Anabolic 500, a cross-sectional survey. Five hundred six male self-reported AAS users (mean age 29.3 yrs) and 771 male self-reported nonusers of AAS (mean age 25.2 yrs) who completed an online survey between February 19 and June 30, 2009. Respondents were recruited from 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. Data were collected on demographics, use of AAS and other performance-enhancing agents, alcohol and illicit drug use, substance dependence disorder, other Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnoses, and history of sexual and/or physical abuse. Most (70.4%) of the AAS users were recreational exercisers who reported using an average of 11.1 performance-enhancing agents in their routine. Compared with nonusers, the AAS users were more likely to meet criteria for substance dependence disorder (23.4% vs 11.2%, p<0.001), report a diagnosis of an anxiety disorder (10.1% vs 6.1%, p=0.010), use cocaine within the past 12 months (11.3% vs 4.7%, p<0.001), and report a history of sexual abuse (6.1% vs 2.7%, p=0.005). Most of the AAS users in this study were recreational exercisers who practiced polypharmacy. The AAS users were more likely than nonusers to meet criteria for substance dependence disorder, report a diagnosis of an anxiety disorder, report recent cocaine use, and have a history of sexual abuse. The information uncovered in this study may help clinicians and researchers develop appropriate intervention strategies for AAS abuse.

Hormonal control of hepatic glycogen metabolism in food-deprived, continuously swimming coho salmon Oncorhynchus kisutch

USGS Publications Warehouse

Vijayan, M.M.; Maule, A.G.; Schreck, C.B.; Moon, T.W.

1993-01-01

The plasma cortisol concentration and liver cytosolic glucocorticoid receptor activities of continuously swimming, food-deprived coho salmon (Oncorhynchus kisutch) did not differ from those of resting, fed fish. Plasma glucose concentration was significantly higher in the exercising, starved fish, but there were no significant differences in either hepatic glycogen concentration or hepatic activities of glycogen phosphorylase, glycogen synthase, pyruvate kinase, or lactate dehydrogenase between the two groups. Total glucose production by hepatocytes did not differ significantly between the two groups; glycogen breakdown accounted for all the glucose produced in the resting, fed fish whereas it explained only 59% of the glucose production in the exercised animals. Epinephrine and glucagon stimulation of glucose production by hepatocytes was decreased in the exercised fish without significantly affecting hepatocyte glycogen breakdown in either group. Insulin prevented glycogen breakdown and enhanced glycogen deposition in exercised fish. The results indicate that food-deprived, continuously swimming coho salmon conserve glycogen by decreasing the responsiveness of hepatocytes to catabolic hormones and by increasing the responsiveness to insulin (anabolic hormone).

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)

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

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; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

Anabolic Androgenic Steroids: Use and Perceived Use in Nonathlete College Students

ERIC Educational Resources Information Center

Berning, Joseph M.; Adams, Kent J.; Debeliso, Mark; Stamford, Bryant A.; Newman, Ian M.

2008-01-01

Objective: The authors investigated the use and perceived use of anabolic androgenic steroids (AAS) among nonathlete college students. Participants: The authors surveyed a sample of 485 nonathlete college students at a major metropolitan university. Methods: They administered a survey on use and perceived use of AAS to the students. Results:…

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

PubMed Central

Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

2015-01-01

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. PMID:19463691

Regucalcin Expression in Bovine Tissues and Its Regulation by Sex Steroid Hormones in Accessory Sex Glands

PubMed Central

Starvaggi Cucuzza, Laura; Divari, Sara; Mulasso, Chiara; Biolatti, Bartolomeo; Cannizzo, Francesca T.

2014-01-01

Regucalcin (RGN) is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle. PMID:25415588

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

New approaches to male non-hormonal contraception.

PubMed

Nya-Ngatchou, Jean-Jacques; Amory, John K

2013-03-01

A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

New approaches to male non-hormonal contraception

PubMed Central

Nya-Ngatchou, Jean-Jacques; Amory, John K.

2012-01-01

A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, Adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials. PMID:22995542

Characterising the muscle anabolic potential of dairy, meat and plant-based protein sources in older adults.

PubMed

Gorissen, Stefan H M; Witard, Oliver C

2018-02-01

The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.

Self-Treatment of Gynecomastia in Bodybuilders Who Use Anabolic Steroids. Case Reports.

ERIC Educational Resources Information Center

Friedl, Karl E.; Yesalis, Charles E.

1989-01-01

Presents four case reports of bodybuilders whose self-administered anabolic steroid programs resulted in gynecomastia, and discusses treatment strategies advocated by some bodybuilders. The actual recommended treatment is complete cessation of drugs. By dispelling unfounded treatment methods, physicians might help discourage such drug use. (SM)

Vibration paradox in orthodontics: Anabolic and catabolic effects

PubMed Central

Alikhani, Mani; Alansari, Sarah; Hamidaddin, Mohammad A.; Sangsuwon, Chinapa; Alyami, Bandar; Thirumoorthy, Soumya N.; Oliveira, Serafim M.; Nervina, Jeanne M.

2018-01-01

Vibration in the form of High Frequency Acceleration (HFA) is anabolic on the craniofacial skeleton in the absence of inflammation. Orthodontic forces trigger an inflammation-dependent catabolic cascade that is crucial for tooth movement. It is unknown what effect HFA has on alveolar bone if applied during orthodontic treatment. The objectives of this study are to examine the effect of HFA on the rate of tooth movement and alveolar bone, and determine the mechanism by which HFA affects tooth movement. Adult Sprague Dawley rats were divided to control, orthodontic force alone (OTM), and different experimental groups that received the same orthodontic forces and different HFA regimens. Orthodontic tooth movement was assessed when HFA parameters, frequency, acceleration, duration of exposure, and direct or indirect application were varied. We found that HFA treatment significantly enhanced the inflammation-dependent catabolic cascade during orthodontic tooth movement. HFA treatment increased inflammatory mediators and osteoclastogenesis, and decreased alveolar bone density during orthodontic tooth movement. Each of the HFA variables produced significant changes in the rate of tooth movement and the effect was PDL-dependent. This is the first report that HFA enhances inflammation-dependent catabolic cascades in bone. The clinical implications of our study are highly significant, as HFA can be utilized to enhance the rate of orthodontic tooth movement during the catabolic phase of treatment and subsequently be utilized to enhance retention during the anabolic remodeling phase after orthodontic forces are removed. PMID:29734391

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. Copyright © 2012 Elsevier Inc. All rights reserved.

Detection of Stimulants and Narcotics by Liquid Chromatography-Tandem Mass Spectrometry and Gas Chromatography-Mass Spectrometry for Sports Doping Control.

PubMed

Ahrens, Brian D; Kucherova, Yulia; Butch, Anthony W

2016-01-01

Sports drug testing laboratories are required to detect several classes of compounds that are prohibited at all times, which include anabolic agents, peptide hormones, growth factors, beta-2 agonists, hormones and metabolic modulators, and diuretics/masking agents. Other classes of compounds such as stimulants, narcotics, cannabinoids, and glucocorticoids are also prohibited, but only when an athlete is in competition. A single class of compounds can contain a large number of prohibited substances and all of the compounds should be detected by the testing procedure. Since there are almost 70 stimulants on the prohibited list it can be a challenge to develop a single screening method that will optimally detect all the compounds. We describe a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) testing method for detection of all the stimulants and narcotics on the World Anti-Doping Agency prohibited list. Urine for LC-MS/MS testing does not require sample pretreatment and is a direct dilute and shoot method. Urine samples for the GC-MS method require a liquid-liquid extraction followed by derivatization with trifluoroacetic anhydride.

Design and synthesis of tricyclic tetrahydroquinolines as a new series of nonsteroidal selective androgen receptor modulators (SARMs).

PubMed

Nagata, Naoya; Miyakawa, Motonori; Amano, Seiji; Furuya, Kazuyuki; Yamamoto, Noriko; Inoguchi, Kiyoshi

2011-03-15

Some tricyclic tetrahydroquinolines (THQs) were found to have the potential of a new series of nonsteroidal selective androgen receptor modulators (SARMs). Compound 5b was first designed and synthesized under our hypothesis based on a four-point pharmacophoric requirement of the 3-carbonyl, 18-methyl, 17-hydroxyl, and 13-quaternary carbon groups of dihydrotestosterone (DHT). It was revealed that this compound exhibits not only a strong androgen receptor (AR) agonistic activity (EC(50)=9.2 nM) but also the highest selectivity in binding affinity to AR among the steroid hormone receptors. Furthermore, this compound showed a weak virilizing effect with retention of the desired anabolic effect as compared with DHT in vivo. Copyright © 2011 Elsevier Ltd. All rights reserved.

Does ethnicity matter in male hormonal contraceptive efficacy?

PubMed Central

Ilani, Niloufar; Liu, Peter Y; Swerdloff, Ronald S; Wang, Christina

2011-01-01

The development of male hormonal contraception has progressed significantly during the last three decades. The ultimate goal is to produce an effective, safe and reversible male method of contraception that are within reach of and can be used by all men globally. This review aims to outline the recent developments in male hormonal contraception with special emphasis on how ethnicity influences acceptability, extent of sperm suppression, and rate of recovery of spermatogenesis. Baseline differences in testicular histomorphology and testosterone metabolism between East Asian and Caucasian men have been reported, but whether this contributes significantly to varying degrees of sperm suppression in response to exogenous testosterone therapy is less known. Testosterone alone male hormonal contraceptive regimens are effective and applicable for East Asian men, and less so for Caucasians. Combinations of progestins with androgens are sufficient to optimize effectiveness of suppression and applicability to all ethnicities. New compounds such as steroidal or non-steroidal selective androgen receptor modulators with dual androgenic and progestational activities are potential compounds for further development as male hormonal contraceptive methods. At the present time, combined androgen and progestin contraceptive regimens appear to be effective, safe, reversible and convenient to use for all men with ethnic, cultural and environmental differences. Further refinements on the hormonal agent, methods of delivery, and dose optimization of the androgen relative to the progestin are necessary. This goal mandates further investment and large clinical trials in multiethnic populations to better define safety and efficacy. PMID:21317912

Variability and dilemmas in harm reduction for anabolic steroid users in the UK: a multi-area interview study

PubMed Central

2014-01-01

Background The UK continues to experience a rise in the number of anabolic steroid-using clients attending harm reduction services such as needle and syringe programmes. Methods The present study uses interviews conducted with harm reduction service providers as well as illicit users of anabolic steroids from different areas of England and Wales to explore harm reduction for this group of drug users, focussing on needle distribution policies and harm reduction interventions developed specifically for this population of drug users. Results The article addresses the complexity of harm reduction service delivery, highlighting different models of needle distribution, such as peer-led distribution networks, as well as interventions available in steroid clinics, including liver function testing of anabolic steroid users. Aside from providing insights into the function of interventions available to steroid users, along with principles adopted by service providers, the study found significant tensions and dilemmas in policy implementation due to differing perspectives between service providers and service users relating to practices, risks and effective interventions. Conclusion The overarching finding of the study was the tremendous variability across harm reduction delivery sites in terms of available measures and mode of operation. Further research into the effectiveness of different policies directed towards people who use anabolic steroids is critical to the development of harm reduction. PMID:24986546

Anabolic Steroid Abuse. National Institute on Drug Abuse Research Report Series.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHHS/PHS), Bethesda, MD.

The use of anabolic steroids is on the increase among athletes as well as other segments of the population. Data from the "Monitoring the Future" study showed a significant increase from 1998 to 1999 in steroid abuse among middle school students. During the same year, there was a decline in the percentage of 12th graders who believed…

[Endocrine disruptors, reproduction and hormone-dependent cancers].

PubMed

Fenichel, Patrick; Brucker-Davis, Françoise; Chevalier, Nicolas

2016-01-01

Endocrine disruptors are natural or synthetic chemical compounds which are present in the environment and which are able to interfere with hormonal regulation pathways and to induce human health deleterious effects. While their precise implication in human health and diseases is still matter of debates, it becomes likely that they have to be considered as risk factors in numerous chronic diseases: developmental and reproductive defects and hormone dependent cancers (present review), metabolic diseases (obesity and type 2 diabetes), neurodevelopmental or neurodegenerative diseases. Low doses exposure during critical windows of exposure such as foetal, perinatal and peri-pubertal periods, or chronic exposure with bioaccumulation in the adipose tissue, and possible synergic effects of several compounds ("cocktail effect") may participate to the genetic/environment interface suspected to participate to the pathophysiology of many diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

New insights into the mechanism and actions of growth hormone (GH) in poultry.

PubMed

Vasilatos-Younken, R; Wang, X H; Zhou, Y; Day, J R; McMurtry, J P; Rosebrough, R W; Decuypere, E; Buys, N; Darras, V; Beard, J L; Tomas, F

1999-10-01

Despite well documented anabolic effects of GH in mammals, a clear demonstration of such responses in domestic poultry is lacking. Recently, comprehensive dose-response studies of GH have been conducted in broilers during late post-hatch development (8 to 9 weeks of age). GH reduced feed intake (FI) and body weight gain in a dose-dependent manner, whereas birds pair-fed to the level of voluntary FI of GH-infused birds did not differ from controls. The reduction in voluntary FI may involve centrally mediated mechanisms, as hypothalamic neuropeptide Y protein and mRNA were reduced with GH, coincident with the maximal depression in FI. Growth of breast muscle was also reduced in a dose-dependent manner. Circulating IGF-I was not enhanced by GH, despite evidence that early events in the GH signaling pathway were intact. A GH dose-dependent increase in circulating 3,3',5-triiodothyronine(T3) paralleled decreases in hepatic 5D-III monodeiodinase activity, whereas 5'D-I activity was not altered. This confirms that a marked hyperthyroid response to GH occurs in late posthatch chickens, resulting from a decrease in the degradative pathway of T3 metabolism. This secondary hyperthyroidism would account for the decreased skeletal muscle mass (52) and lack of enhanced IGF-I (53) in GH-treated birds. Based upon these studies, it is now evident that GH does in fact have significant effects in poultry, but metabolic responses may confound the anabolic potential of the hormone.

Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

PubMed Central

Wolf, Michael; Lossdörfer, Stefan; Römer, Piero; Bastos Craveiro, Rogerio; Deschner, James; Jäger, Andreas

2014-01-01

High mobility group box protein-1 (HMGB1) is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL) cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL) were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement. PMID:25525297

Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem.

PubMed

Rahnema, C D; Crosnoe, L E; Kim, E D

2015-03-01

Colloquially referred to by various misleading monikers ('pro-hormones', 'natural steroids', 'testosterone boosters', etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids (AAS) remain available in over-the-counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over-the-counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies' failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace. © 2015 American Society of Andrology and European Academy of Andrology.

Comparison between triple quadrupole, time of flight and hybrid quadrupole time of flight analysers coupled to liquid chromatography for the detection of anabolic steroids in doping control analysis.

PubMed

Pozo, Oscar J; Van Eenoo, Peter; Deventer, Koen; Elbardissy, Hisham; Grimalt, Susana; Sancho, Juan V; Hernandez, Felix; Ventura, Rosa; Delbeke, Frans T

2011-01-17

Triple quadrupole (QqQ), time of flight (TOF) and quadrupole-time of flight (QTOF) analysers have been compared for the detection of anabolic steroids in human urine. Ten anabolic steroids were selected as model compounds based on their ionization and the presence of endogenous interferences. Both qualitative and quantitative analyses were evaluated. QqQ allowed for the detection of all analytes at the minimum required performance limit (MRPL) established by the World Anti-Doping Agency (between 2 and 10 ng mL(-1) in urine). TOF and QTOF approaches were not sensitive enough to detect some of the analytes (3'-hydroxy-stanozolol or the metabolites of boldenone and formebolone) at the established MRPL. Although a suitable accuracy was obtained, the precision was unsatisfactory (RSD typically higher than 20%) for quantitative purposes irrespective of the analyser used. The methods were applied to 30 real samples declared positives either for the misuse of boldenone, stanozolol and/or methandienone. Most of the compounds were detected by every technique, however QqQ was necessary for the detection of some metabolites in a few samples. Finally, the possibility to detect non-target steroids has been explored by the use of TOF and QTOF. The use of this approach revealed that the presence of boldenone and its metabolite in one sample was due to the intake of androsta-1,4,6-triene-3,17-dione. Additionally, the intake of methandienone was confirmed by the post-target detection of a long-term metabolite. Copyright © 2010 Elsevier B.V. All rights reserved.

The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration

PubMed Central

Villanueva, I.; Alva-Sánchez, C.; Pacheco-Rosado, J.

2013-01-01

Reactive oxygen species (ROS) are oxidizing agents amply implicated in tissue damage. ROS production is inevitably linked to ATP synthesis in most cells, and the rate of production is related to the rate of cell respiration. Multiple antioxidant mechanisms limit ROS dispersion and interaction with cell components, but, when the balance between ROS production and scavenging is lost, oxidative damage develops. Many traits of aging are related to oxidative damage by ROS, including neurodegenerative diseases. Thyroid hormones (THs) are a major factor controlling metabolic and respiratory rates in virtually all cell types in mammals. The general metabolic effect of THs is a relative acceleration of the basal metabolism that includes an increase of the rate of both catabolic and anabolic reactions. THs are related to oxidative stress not only by their stimulation of metabolism but also by their effects on antioxidant mechanisms. Thyroid dysfunction increases with age, so changes in THs levels in the elderly could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear. In this review, we analyze the participation of thyroid hormones on ROS production and oxidative stress, and the way the changes in thyroid status in aging are involved in neurodegenerative diseases. PMID:24386502

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)

Steroid hormonal bioactivities, culprit natural and synthetic hormones and other emerging contaminants in waste water measured using bioassays and UPLC-tQ-MS.

PubMed

Houtman, Corine J; Ten Broek, Rob; Brouwer, Abraham

2018-07-15

Emission of compounds with biological activities from waste water treatment plant (WWTP) effluents into surface waters is a topic of concern for ecology and drinking water quality. We investigated the occurrence of hormone-like activities in waste water sample extracts from four Dutch WWTPs and pursued to identify compounds responsible for them. To this aim, in vitro reporter gene bioassays for androgenic, anti-androgenic, estrogenic, glucocorticoid and progestogenic activity and a UPLC-tQ-MS target analysis method for 25 steroid hormones used in high volumes in pharmacy were applied. Principal component analysis of the data was performed to further characterize the detected activities and compounds. All five types of activities tested were observed in the WWTP samples. Androgenic and estrogenic activities were almost completely removed during WW treatment, anti-androgenic activity was only found in treated WW. Glucocorticoid and progestogenic activities persisted throughout the treatment. The androgenic activity in both influent could predominantly be attributed to the presence of androstenedione and testosterone. Anti-androgenic activity was explained by the presence of cyproterone acetate. The glucocorticoid activity in influent was fully explained by prednicarbate, triamcinolone acetonide, dexamethasone and amcinonide. In effluent however, detected hormones could only explain 10-32% of the activity, indicating the presence of unknown glucocorticoids or their metabolites in effluent. Progesterone and levonorgestrel could explain the observed progestogenic activity. The principle component analysis confirmed the way in which hormones fit in the spectrum of other emerging contaminants concerning occurrence and fate in WWTPs. Copyright © 2018 Elsevier B.V. All rights reserved.

Hormones in international meat production: biological, sociological and consumer issues.

PubMed

Galbraith, Hugh

2002-12-01

Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate

The Effect of Steroid Hormones on the Physical Performance of Boys and Girls During an Olympic Weightlifting Competition.

PubMed

Crewther, Blair; Obminski, Zbigniew; Cook, Christian

2016-11-01

To examine the steroid hormone effect on the physical performance of young athletes during an Olympic weightlifting competition. 26 boys and 26 girls were monitored across 2 weightlifting competitions. Pre- and post-competition testosterone (T), cortisol (C) and dehydroepiandrosterone-sulfate (DHEA-s) were measured in blood, with pre-event free T (FT) and the free androgen index (FAI) calculated. Body mass (BM) and weightlifting performance were recorded. The boys had a larger BM, superior performance with more T, FT and a higher FAI than girls (p < .01). Although C (32%) and DHEA-s (8%) levels were elevated across competition, no sex differences in hormone reactivity were seen. In boys, DHEA-s correlated with performance (r = .46), but not after controlling for BM (r = .14). For girls, T correlated with performance (r = -0.51) after BM was controlled. The sex differences that emerge during puberty were observable, whereby the boys were larger and stronger with a more anabolic profile than girls. Individual DHEA-s (boys) and T (girls) levels were related to performance, but BM appeared to be acting as a mediating (boys) or suppressing (girls) variable. This adds new insight regarding the hormonal contribution to competitive performance in young athletes.

GC-MS quantitative analysis of black market pharmaceutical products containing anabolic androgenic steroids seized by the Brazilian Federal Police.

PubMed

Neves, Diana Brito da Justa; Caldas, Eloisa Dutra

2017-06-01

The use of counterfeit or substandard medicines can have an important health impact, resulting in therapeutic failure, be toxic or even cause death. Anabolic steroids are a frequent target for counterfeiters worldwide, being the second most frequent counterfeited class in Brazil. The aims of this work were to optimize and validate a GC-MS method for the quantitative determination of anabolic steroids in tablet, aqueous suspension and oil solution forms, and to analyze pharmaceutical products sent to Brazilian Federal Police (BFP) for forensic analysis. Sample preparation included extraction with methanol in ultrasonic bath followed by centrifugation. The method was successfully validated and 345 samples of pharmaceutical products were analyzed (328 medicines and 17 dietary supplements). About 42% of the medicines were counterfeits, 28.7% of tablets, 12.0% of suspensions and 65.2% of oil solutions; 11% were considered substandards. Five dietary supplements contained undeclared anabolic steroids, including two containing methandrostenolone at 5.4 and 5.8mg/capsule, equivalent to levels found in medicines. The proposed method is suitable for implementation in routine analysis for identification of counterfeits and substandard products. The analytical results show the need to raise awareness of consumers over the risks from the consumption of anabolic steroids from the clandestine market and for more incisive actions from government agencies aiming at decreasing the availability of these products. Copyright © 2017 Elsevier B.V. All rights reserved.

Anabolic Androgenic Steroid Use in Teens: Prevalence, Demographics, and Perception of Effects

ERIC Educational Resources Information Center

Lorang, Melissa; Callahan, Bryan; Cummins, Kevin M.; Achar, Suraj; Brown, Sandra A.

2011-01-01

Multiple risks are associated with early use of anabolic androgenic steroids, yet public understanding is limited and teen use not uncommon. The present study surveyed 4,231 high school students to understand prevalence of use, association with athletics and other substance use and expectations of drug effects. While overall rates of steroid use…

A selective androgen receptor modulator for hormonal male contraception.

PubMed

Chen, Jiyun; Hwang, Dong Jin; Bohl, Casey E; Miller, Duane D; Dalton, James T

2005-02-01

The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies, including hormonal male contraception. The identification of an orally bioavailable SARM with the ability to mimic the central and peripheral androgenic and anabolic effects of testosterone would represent an important step toward the "male pill". We characterized the in vitro and in vivo pharmacologic activity of (S)-3-(4-chloro-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide (C-6), a novel SARM developed in our laboratories. C-6 was identified as an androgen receptor (AR) agonist with high AR binding affinity (K(i) = 4.9 nM). C-6 showed tissue-selective pharmacologic activity with higher anabolic activity than androgenic activity in male rats. The doses required to maintain the weight of the prostate, seminal vesicles, and levator ani muscle to half the size of the maximum effects (i.e., ED(50)) were 0.78 +/- 0.06, 0.88 +/- 0.1, and 0.17 +/- 0.04 mg/day, respectively. As opposed to other SARMs, gonadotropin levels in C-6-treated groups were significantly lower than control values. C-6 also significantly decreased serum testosterone concentration in intact rats after 2 weeks of treatment. Marked suppression of spermatogenesis was observed after 10 weeks of treatment with C-6 in intact male rats. Pharmacokinetic studies of C-6 in male rats revealed that C-6 was well absorbed after oral administration (bioavailability 76%), with a long (6.3 h) half-life at a dose of 10 mg/kg. These studies show that C-6 mimicked the in vivo pharmacologic and endocrine effects of testosterone while maintaining the oral bioavailability and tissue-selective actions of nonsteroidal SARMs.

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

PubMed

Solomon, Lauren A; Podder, Shreya; He, Jessica; Jackson-Chornenki, Nicholas L; Gibson, Kristen; Ziliotto, Rachel G; Rhee, Jess; DeKoter, Rodney P

2017-05-15

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1 , an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. Copyright © 2017 American Society for Microbiology.

High protein diets do not attenuate decrements in testosterone and IGF-I during energy deficit.

PubMed

Henning, Paul C; Margolis, Lee M; McClung, James P; Young, Andrew J; Pasiakos, Stefan M

2014-05-01

Energy deficit (ED) diminishes fat-free mass (FFM) with concomitant reductions in anabolic hormone secretion. A modest increase in protein to recommended dietary allowance (RDA) levels during ED minimally attenuates decrements in insulin-like growth factor-I (IGF-I). The impact of dietary protein above the RDA on circulating anabolic hormones and their relationships with FFM in response to ED are not well described. Thirty-three adults were assigned diets providing protein at 0.8 (RDA), 1.6 (2×-RDA), and 2.4 (3×-RDA) g/kg/d for 31days. Testosterone, sex-hormone binding globulin (SHBG) and IGF-I system components were assessed after a 10-day period of weight-maintenance (WM) and after a 21-day period of ED (40%) achieved by an increase in energy expenditure and decreased energy intake. Associations between the change in FFM and anabolic hormone levels were determined. As compared to WM and regardless of dietary protein intake, total and free testosterone, total IGF-I, and acid-labile subunit decreased (P<0.05), whereas SHBG and IGF binding proteins-1, -2, and -3 increased (P<0.05) during ED. There were no energy-by-protein interactions on any hormones or IGF-I system components measured. Changes in FFM in response to ED were negatively associated with acid-labile subunit (ALS) (r=-0.62, P<0.05) in 2×-RDA; however, no other relationships were observed. Consuming a high protein diet does not impact the androgenic and IGF-I system response to ED. These data suggest that the protective effects of high protein diets on FFM during ED are likely not influenced by anabolic hormone concentrations. Published by Elsevier Inc.

Psychomotor and Motor Speed in Power Athletes Self-Administering Testosterone and Anabolic Steroids.

ERIC Educational Resources Information Center

Era, Pertti; And Others

1988-01-01

Self-administered testosterone and anabolic steroids resulted in insignificant improvement in psychomotor and motor speed tests of power athletes. This study is part of a larger study on the effects of such drugs on endocrinology, metabolism and neuromuscular functions. Methodolgy and results are discussed. (Author/JL)

In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

PubMed Central

Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

2015-01-01

This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

Lactoferricin Enhances BMP7-Stimulated Anabolic Pathways in Intervertebral Disc Cells

PubMed Central

Ellman, Michael B; Kim, Jaesung; An, Howard S; Chen, Di; Kc, Ranjan; Li, Xin; Xiao, Guozhi; Yan, Dongyao; Suh, Joon; van Wijnen, Andre J.; Wang, James H-C; Kim, Su-Gwan; Im, Hee-Jeong

2013-01-01

Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral (IVD) matrix and cell homeostasis. Similarly, lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc (IVD) matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin (BMP receptor antagonist) and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration. PMID:23644135

Lactoferricin enhances BMP7-stimulated anabolic pathways in intervertebral disc cells.

PubMed

Ellman, Michael B; Kim, Jaesung; An, Howard S; Chen, Di; Kc, Ranjan; Li, Xin; Xiao, Guozhi; Yan, Dongyao; Suh, Joon; van Wjnen, Andre J; Wang, James H-C; Kim, Su-Gwan; Im, Hee-Jeong

2013-07-25

Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral disc (IVD) matrix and cell homeostasis. Similarly, Lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the gene expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of Noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of Noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration. Copyright © 2013 Elsevier B.V. All

Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase.

PubMed

Armour, K E; Armour, K J; Gallagher, M E; Gödecke, A; Helfrich, M H; Reid, D M; Ralston, S H

2001-02-01

Nitric oxide (NO) is a pleiotropic signaling molecule that is produced by bone cells constitutively and in response to diverse stimuli such as proinflammatory cytokines, mechanical strain, and sex hormones. Endothelial nitric oxide synthase (eNOS) is the predominant NOS isoform expressed in bone, but its physiological role in regulating bone metabolism remains unclear. Here we studied various aspects of bone metabolism in female mice with targeted disruption of the eNOS gene. Mice with eNOS deficiency (eNOS KO) had reduced bone mineral density, and cortical thinning when compared with WT controls and histomorphometric analysis of bone revealed profound abnormalities of bone formation, with reduced osteoblast numbers, surfaces and mineral apposition rate. Studies in vitro showed that osteoblasts derived from eNOS KO mice had reduced rates of growth when compared with WT and were less well differentiated as reflected by lower levels of alkaline phosphatase activity. Mice with eNOS deficiency lost bone normally following ovariectomy but exhibited a significantly blunted anabolic response to high dose exogenous estrogen. We conclude that the eNOS pathway plays an essential role in regulating bone mass and bone turnover by modulating osteoblast function.

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.

Determinants of Anabolic-Androgenic Steroid Risk Perceptions in Youth Populations: A Multivariate Analysis

ERIC Educational Resources Information Center

Denham, Bryan E.

2009-01-01

Grounded conceptually in social cognitive theory, this research examines how personal, behavioral, and environmental factors are associated with risk perceptions of anabolic-androgenic steroids. Ordinal logistic regression and logit log-linear models applied to data gathered from high-school seniors (N = 2,160) in the 2005 Monitoring the Future…

Nandrolone androgenic hormone presents genotoxic effects in different cells of mice.

PubMed

do Carmo, Carolina Almeida; Gonçalves, Álvaro Luiz Martini; Salvadori, Daisy Maria Fávero; Maistro, Edson Luis

2012-10-01

Nandrolone is an androgenic-anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca-durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg⁻¹ body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE-NCE ratio). The results showed a significant dose-related increase in the frequency of DNA damage in leukocytes, liver, bone marrow, brain and testicle cells at the three tested doses and a significant increase of the micronucleated polychromatic erythrocytes at all tested doses. Under our experimental conditions, the nandrolone steroid hormone showed genotoxic and clastogenic effects when administered subcutaneously to mice. Copyright © 2011 John Wiley & Sons, Ltd.

[New addictions in the third millennium: anabolic steroids as a substance of abuse].

PubMed

Roccella, M; Paternò, G; Bonanno, M; Tusa, F; Testa, D

2005-06-01

The abuse of anabolic steroids is emerging as a psychosocially significant issue. In the last few years the use of the substances has shifted from professional sports to amateur sports and certain occupations (bouncers, models, etc.). In the literature, steroid users are portrayed as multidrug users who engage in dangerous and aggressive behavior towards themselves and others. This study looks into the habits, lifestyles and psychological profiles of a group of subjects who make regular use of sports centres in the city of Palermo, Italy, with the aim of establishing how the abuse of anabolic substances is associated with a specific lifestyle and particular psychosocial behaviour. A revision of the American Massachusetts Youth Risk Survey questionnaire (1993), adapted for the Italian context, and a personality assessment scale, The Adjective Check List (1980), were administered to a group of 71 subjects. Fifteen of these subjects admitted taking steroids with differing frequencies. Using Spearman's rho rank correlation, repeated use of anabolic steroids was found to be correlated with abuse of other types of drugs, risk behavior and a distinct personality pattern. Steroid abuse was found to be significantly correlated (r = 0.35, 0.31, 0.30, 0.28, P < 0.01) with illegal drug use (LSD, cocaine and heroin). It is therefore imperative to develop studies and analyses to investigate more thoroughly the phenomenon and its related psychological and social context in order to lay the foundations for a targeted prevention programme, especially in countries such as Italy where this type of drug abuse is still largely unrecognised and risks degenerating into a new, full-blown social disease.

Influence of sex steroid hormones on the adolescent brain and behavior: An update

PubMed Central

Vigil, Pilar; del Río, Juan Pablo; Carrera, BÁrbara; ArÁnguiz, Florencia C.

2016-01-01

This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical “organizational window” for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary: The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental “organizational window” during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders. PMID:27833209

The UK Sport perspective on detecting growth hormone abuse.

PubMed

Stow, M R; Wojek, N; Marshall, J

2009-08-01

Human growth hormone (hGH) is seen as a doping risk in sport because of its possible anabolic and lipolytic effects. As a result of this hGH is prohibited for athletes to use both in and out-of-competition by the World Anti-Doping Agency (WADA) requiring Anti-Doping Organisations to work with research teams in identifying ways to detect hGH abuse. This paper reviews and discusses the UK Sport perspective on the challenges faced in detecting hGH and in particular draws upon the experiences gained during the collaborative efforts with the GH-2004 research team in achieving the implementation of the Marker Method for hGH detection. In 2008 significant progress has been made; there is one test for detecting HGH approved for use in anti-doping and a second detection method pending. This is a strong reflection of the ongoing research efforts in anti-doping and the progress being made by the Anti-Doping Organisations in reducing the risk that doping poses to sport.

Driving mechanisms of passive and active transport across cellular membranes as the mechanisms of cell metabolism and development as well as the mechanisms of cellular distance reactions on hormonal expression and the immune response.

PubMed

Ponisovskiy, M R

2011-01-01

The article presents mechanisms of cell metabolism, cell development, cell activity, and maintenance of cellular stability. The literature is reviewed from the point of view of these concepts. The balance between anabolic and catabolic processes induces chemical potentials in the extracellular and intracellular media. The chemical potentials of these media are defined as the driving forces of both passive and active transport of substances across cellular membranes. The driving forces of substance transport across cellular membranes as in cellular metabolism and in immune responses and hormonal expressions are considered in the biochemical and biophysical models, reflecting the mechanisms for maintenance of stability of the internal medium and internal energy of an organism. The interactions of passive transport and active transport of substances across cellular walls promote cell proliferation, as well as the mechanism of cellular capacitors, promoting remote reactions across distance for hormonal expression and immune responses. The offered concept of cellular capacitors has given the possibility to explain the mechanism of remote responses of cells to new situations, resulting in the appearance of additional agents. The biophysical model develops an explanation of some cellular functions: cellular membrane action have been identified with capacitor action, based on the similarity of the structures and as well as on similarity of biophysical properties of electric data that confirm the action of the compound-specific interactions of cells within an organism, promoting hormonal expressions and immune responses to stabilize the thermodynamic system of an organism. Comparison of a cellular membrane action to a capacitor has given the possibility for the explanations of exocytosis and endocytosis mechanisms, internalization of the receptor-ligand complex, selection as a receptor reaction to a ligand by immune responses or hormonal effects, reflecting cellular

Highly Sensitive and High-Throughput Analysis of Plant Hormones Using MS-Probe Modification and Liquid Chromatography–Tandem Mass Spectrometry: An Application for Hormone Profiling in Oryza sativa

PubMed Central

Kojima, Mikiko; Kamada-Nobusada, Tomoe; Komatsu, Hirokazu; Takei, Kentaro; Kuroha, Takeshi; Mizutani, Masaharu; Ashikari, Motoyuki; Ueguchi-Tanaka, Miyako; Matsuoka, Makoto; Suzuki, Koji; Sakakibara, Hitoshi

2009-01-01

We have developed a highly sensitive and high-throughput method for the simultaneous analysis of 43 molecular species of cytokinins, auxins, ABA and gibberellins. This method consists of an automatic liquid handling system for solid phase extraction and ultra-performance liquid chromatography (UPLC) coupled with a tandem quadrupole mass spectrometer (qMS/MS) equipped with an electrospray interface (ESI; UPLC-ESI-qMS/MS). In order to improve the detection limit of negatively charged compounds, such as gibberellins, we chemically derivatized fractions containing auxin, ABA and gibberellins with bromocholine that has a quaternary ammonium functional group. This modification, that we call ‘MS-probe’, makes these hormone derivatives have a positive ion charge and permits all compounds to be measured in the positive ion mode with UPLC-ESI-qMS/MS in a single run. Consequently, quantification limits of gibberellins increased up to 50-fold. Our current method needs <100 mg (FW) of plant tissues to determine phytohormone profiles and enables us to analyze >180 plant samples simultaneously. Application of this method to plant hormone profiling enabled us to draw organ distribution maps of hormone species in rice and also to identify interactions among the four major hormones in the rice gibberellin signaling mutants, gid1-3, gid2-1 and slr1. Combining the results of hormone profiling data with transcriptome data in the gibberellin signaling mutants allows us to analyze relationships between changes in gene expression and hormone metabolism. PMID:19369275

Performance-Enhancing Drugs and Teen Athletes

MedlinePlus

... search. Accessed March 3, 2018. Steroid precursors and adolescent health. The Hormone Foundation. https://www.hormone.org/diseases-and-conditions/children-and-teen-health/steroid-precursors. Accessed March 3, 2018. Anabolic steroids. ...

Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study.

PubMed

Rasmussen, Jon Jarløv; Selmer, Christian; Østergren, Peter Busch; Pedersen, Karen Boje; Schou, Morten; Gustafsson, Finn; Faber, Jens; Juul, Anders; Kistorp, Caroline

2016-01-01

Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. Former AAS abusers exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely

The C-terminal fragment of parathyroid hormone-related peptide promotes bone formation in diabetic mice with low-turnover osteopaenia

PubMed Central

Lozano, D; Fernández-de-Castro, L; Portal-Núñez, S; López-Herradón, A; Dapía, S; Gómez-Barrena, E; Esbrit, P

2011-01-01

BACKGROUND AND PURPOSE Current data suggest that parathyroid hormone (PTH)-related peptide (PTHrP) domains other than the N-terminal PTH-like domain contribute to its role as an endogenous bone anabolic factor. PTHrP-107-139 inhibits bone resorption, a fact which has precluded an unequivocal demonstration of its possible anabolic action in vivo. We thus sought to characterize the osteogenic effects of this peptide using a mouse model of diabetic low-turnover osteopaenia. EXPERIMENTAL APPROACH PTHrP-107-139 was administered to streptozotocin-induced diabetic mice, with or without bone marrow ablation, for 13 days. Osteopaenia was confirmed by dual-energy X-ray absorptiometry and microcomputed tomography analysis. Histological analysis was performed on paraffin-embedded bone tissue sections by haematoxylin/eosin and Masson's staining, and tartrate-resistent acid phosphatase immunohistochemistry. Mouse bone marrow stromal cells and osteoblastic MC3T3-E1 cells were cultured in normal and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed by real-time PCR, and PTHrP and the PTH1 receptor protein expression by Western blot analysis. KEY RESULTS PTHrP-107-139 reversed the alterations in bone structure and osteoblast function, and also promoted bone healing after marrow ablation without affecting the number of osteoclast-like cells in diabetic mice. This peptide also reversed the high-glucose-induced changes in osteogenic differentiation in both bone marrow stromal cells and the more differentiated MC3T3-E1 cells. CONCLUSIONS AND IMPLICATIONS These findings demonstrate that PTHrP-107-139 promotes bone formation in diabetic mice. This mouse model and in vitro cell cultures allowed us to identify various anabolic effects of this peptide in this scenario. PMID:21175568

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

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.

Environments, risk and health harms: a qualitative investigation into the illicit use of anabolic steroids among people using harm reduction services in the UK.

PubMed

Kimergård, Andreas; McVeigh, Jim

2014-06-04

The illicit use of anabolic steroids among the gym population continues to rise, along with the number of steroid using clients attending harm reduction services in the UK. This presents serious challenges to public health. Study objectives were to account for the experiences of anabolic steroid users and investigate how 'risk environments' produce harm. Qualitative face-to-face interviews with 24 users of anabolic steroids engaged with harm reduction services in the UK. Body satisfaction was an important factor when deciding to start the use of anabolic steroids. Many users were unaware of the potential dangers of using drugs from the illicit market, whereas some had adopted a range of strategies to negotiate the hazards relating to the use of adulterated products, including self-experimentation to gauge the perceived efficacy and unwanted effects of these drugs. Viewpoints, first-hand anecdotes, norms and practices among groups of steroid users created boundaries of 'sensible' drug use, but also promoted practices that may increase the chance of harms occurring. Established users encouraged young users to go to harm reduction services but, at the same time, promoted risky injecting practices in the belief that this would enhance the efficacy of anabolic steroids. Current steroid-related viewpoints and practices contribute to the risk environment surrounding the use of these drugs and may undermine the goal of current public health strategies including harm reduction interventions. The level of harms among anabolic steroid users are determined by multiple and intertwining factors, in addition to the harms caused by the pharmacological action or injury and illness associated with incorrect injecting techniques. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

PubMed

Lindblom, Jonas; Kindlundh, Anna M S; Nyberg, Fred; Bergström, Lena; Wikberg, Jarl E S

2003-10-03

Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

Adverse effects of doping with anabolic androgenic steroids (AAS) in competitive athletics, recreational sports and bodybuilding.

PubMed

Vorona, Elena; Nieschlag, Eberhard

2018-02-19

Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of athletes admits to their unabated application. In competitive athletics, bodybuilding and in recreational sports anabolic androgenic steroids (AAS) continue to be the substances most abused. This review summarizes the side effects of AAS abuse on organs and system functions in both sexes. High doses of AAS cause a significant increase of erythrocytes und haemoglobin concentration, which may lead to thromboembolism, intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence of arrhythmias, atherosclerosis, concentric left-ventricular myocardial hypertrophy with impaired diastolic function and also sudden cardiac death. Changes of liver function and structure, up to hepatocellular carcinoma, have been described, mainly in cases of chronic misuse of 17α-alkylated AAS. Sleeplessness, increased irritability, depressive mood status are often observed in AAS abuse. In former AAS abusers depression, anxiety and melancholy may persist for many years. Due to negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of spermatogenesis up to azoospermia. In women the changes most often caused by AAS abuse are hirsutism, irreversible deepening of voice, dysmenorrhoea, secondary amenorrhoea with anovulation and infertility. AAS abuse notwithstanding, under clinical conditions testosterone remains the most important hormone for substitution therapy of male hypogonadism.

Exercise reinforcement, stress, and β-endorphins: an initial examination of exercise in anabolic-androgenic steroid dependence.

PubMed

Hildebrandt, Tom; Shope, Sydney; Varangis, Eleanna; Klein, Diane; Pfaff, Donald W; Yehuda, Rachel

2014-06-01

Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Plant hormones and ecophysiology of conifers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davies, W.J.

1995-07-01

Over the past 30 years, there have been very substantial fluctuations in the interests of plant scientists in the involvement of plant growth regulators in the control of physiology, growth, and development of plants. In the years following the identification of the five major classes of growth regulators and identification of other groups of compounds of somewhat more restricted interest, an enormous number of papers reported the effects of hormones applied externally to a very wide range of plants. During this period, it became very fashionable to compare effects of hormones with the effects of the environment on developmental andmore » physiological phenomena and to suggest a regulatory role for the hormone(s) in the processes under consideration. Ross et al. (1983) have published a very comprehensive survey of the effects of growth regulators applied externally to conifers, and even 10 years later, it is difficult to improve on what they have done. Nevertheless, in the light of recent changes in our understanding of how growth regulators may work, it is necessary to reexamine this field and ask what we really know about the involvement of growth regulators in the ecophysiology of conifers.« less

Human biological monitoring of suspected endocrine-disrupting compounds

PubMed Central

Faniband, Moosa; Lindh, Christian H; Jönsson, Bo AG

2014-01-01

Endocrine-disrupting compounds are exogenous agents that interfere with the natural hormones of the body. Human biological monitoring is a powerful method for monitoring exposure to endocrine disrupting compounds. In this review, we describe human biological monitoring systems for different groups of endocrine disrupting compounds, polychlorinated biphenyls, brominated flame retardants, phthalates, alkylphenols, pesticides, metals, perfluronated compounds, parabens, ultraviolet filters, and organic solvents. The aspects discussed are origin to exposure, metabolism, matrices to analyse, analytical determination methods, determinants, and time trends. PMID:24369128

Classification of auxin plant hormones by interaction property similarity indices

NASA Astrophysics Data System (ADS)

Tomić, Sanja; Gabdoulline, Razif R.; Kojić-Prodić, Biserka; Wade, Rebecca C.

1998-01-01

Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds were defined: strongly active, weakly active with weak antiauxin behaviour, inactive and inhibitory. All compounds were modeled in two low-energy conformations, `P' and `T', so as to obtain the best match to the `planar' and `tilted' conformations, respectively, of indole 3-acetic acid. Each set of conformers was superimposed separately using several different alignment schemes. Molecular interaction energy fields were computed for each molecule with five different chemical probes and then compared by computing similarity indices. Similarity analysis showed that the classes are on average distinguishable, with better differentiation achieved for the T conformers than the P conformers. This indicates that the T conformation might be the active one. Further, a screening was developed which could distinguish compounds with auxin activity from inactive compounds and most antiauxins using the T conformers. The classifications rationalize ambiguities in activity data found in the literature and should be of value in predicting the activities of new plant growth substances and herbicides.

Exercise as an anabolic intervention in patients with end-stage renal disease.

PubMed

Ikizler, T Alp

2011-01-01

Muscle wasting and accompanying structural derangements leading to abnormalities in muscle function, exercise performance, and physical activity are common in patients with end-stage renal disease. Therefore, several studies have been performed examining the effects of exercise in this particular patient population. Most of the studies have assessed the effects of cardiopulmonary fitness training, whereas a few have examined the role of resistance (i.e., strength) training. Despite the proven efficacy of resistance exercise as an anabolic intervention in the otherwise healthy elderly population and certain chronic disease states, recent studies in patients on maintenance hemodialysis have not been encouraging in terms of long-term improvements in markers of muscle mass. Preliminary studies indicated that a combination of simultaneous exercise and nutritional supplementation could augment the anabolic effects of exercise, at least in the acute setting. However, a recent randomized clinical trial failed to show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone. Further research is necessary to both understand the observed lack of obvious benefits and strategies to improve the exercise regimens in patients with end-stage renal disease. Published by Elsevier Inc.

Dehydroepiandrosterone and dehydroepiandrosterone sulfate: anabolic, neuroprotective, and neuroexcitatory properties in military men.

PubMed

Taylor, Marcus K

2013-01-01

Evidence links dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) to crucial military health issues, including operational stress, resilience, and traumatic brain injury. This study evaluated the anabolic, neuroprotective, and neuroexcitatory properties of DHEA(S) in healthy military men. A salivary sample was obtained from 42 men and assayed for DHEA(S), testosterone, nerve growth factor (NGF; which supports nerve cell proliferation), and salivary alpha amylase (sAA; a proxy of sympathetic nervous system function). Separate regression analyses were conducted with DHEA and DHEAS as independent variables, and testosterone, NGF, and sAA as dependent variables, respectively. The models explained 23.4% of variance in testosterone (p < 0.01), 17.2% of variance in NGF (p < 0.01), and 7.4% of variance in sAA (p = 0.09). Standardized beta coefficients revealed that DHEA independently influenced testosterone (beta = 0.40, p < 0.01), whereas DHEAS independently influenced NGF (beta = 0.48, p < 0.01) and sAA (beta = 0.36, p < 0.05). DHEA demonstrated anabolic properties, whereas DHEAS demonstrated neuroprotective and neuroexcitatory properties in military men. This area of study has broad implications for stress inoculation, traumatic brain injury rehabilitation, and regenerative medicine in military personnel.

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

The Contribution of Social Media to Body Dissatisfaction, Eating Disorder Symptoms, and Anabolic Steroid Use Among Sexual Minority Men

PubMed Central

Murray, Stuart B.; Krug, Isabel; McLean, Siân A.

2018-01-01

Abstract Social media has been associated with body dissatisfaction and eating disorder symptoms among young women and adolescent girls. However, despite notable evidence of susceptibility to body image pressures, it remains unknown whether these associations generalize to sexual minority men. A nationwide sample of 2,733 sexual minority men completed an online survey advertised to Australian and New Zealand users of a popular dating app. Participants answered questions about how frequently they used 11 different social media platforms in addition to questions about their dating app use, body image, eating disorder symptoms, and anabolic steroids. Facebook, Youtube, Instagram, and Snapchat were the most frequently used social media platforms. A pattern of small-sized and positive associations emerged between social media use and body dissatisfaction, eating disorder symptoms, and thoughts about using anabolic steroids. Facebook, Instagram, and Snapchat evidenced the strongest associations. The associations of social media use with both muscularity dissatisfaction and eating disorder symptoms were stronger for image-centric social media platforms (e.g., Instagram) than nonimage-centric platforms (e.g., Wordpress); no differences were observed for body fat dissatisfaction, height dissatisfaction, or thoughts about using anabolic steroids. Previously documented associations of social media use with body dissatisfaction and related variables among women and girls appear to generalize to sexual minority men. Social media platforms that more centrally involve imagery may be of greater concern than nonimage-centric platforms. Additional research with sexual minority men is needed to elucidate the distinctions between adaptive and maladaptive social media use in the context of body dissatisfaction, eating disorders, and anabolic steroid use. PMID:29363993

The Contribution of Social Media to Body Dissatisfaction, Eating Disorder Symptoms, and Anabolic Steroid Use Among Sexual Minority Men.

PubMed

Griffiths, Scott; Murray, Stuart B; Krug, Isabel; McLean, Siân A

2018-03-01

Social media has been associated with body dissatisfaction and eating disorder symptoms among young women and adolescent girls. However, despite notable evidence of susceptibility to body image pressures, it remains unknown whether these associations generalize to sexual minority men. A nationwide sample of 2,733 sexual minority men completed an online survey advertised to Australian and New Zealand users of a popular dating app. Participants answered questions about how frequently they used 11 different social media platforms in addition to questions about their dating app use, body image, eating disorder symptoms, and anabolic steroids. Facebook, Youtube, Instagram, and Snapchat were the most frequently used social media platforms. A pattern of small-sized and positive associations emerged between social media use and body dissatisfaction, eating disorder symptoms, and thoughts about using anabolic steroids. Facebook, Instagram, and Snapchat evidenced the strongest associations. The associations of social media use with both muscularity dissatisfaction and eating disorder symptoms were stronger for image-centric social media platforms (e.g., Instagram) than nonimage-centric platforms (e.g., Wordpress); no differences were observed for body fat dissatisfaction, height dissatisfaction, or thoughts about using anabolic steroids. Previously documented associations of social media use with body dissatisfaction and related variables among women and girls appear to generalize to sexual minority men. Social media platforms that more centrally involve imagery may be of greater concern than nonimage-centric platforms. Additional research with sexual minority men is needed to elucidate the distinctions between adaptive and maladaptive social media use in the context of body dissatisfaction, eating disorders, and anabolic steroid use.

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.

PubMed

Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H

2016-01-01

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. Published by Elsevier Inc.

[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. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Roles of GSK3 in metabolic shift toward abnormal anabolism in cell senescence.

PubMed

Kim, You-Mie; Seo, Yong-Hak; Park, Chan-Bae; Yoon, Soo-Han; Yoon, Gyesoon

2010-07-01

Diverse metabolic alterations, including mitochondrial dysfunction, have often been reported as characteristic phenotypes of senescent cells. However, the overall consequence of senescent metabolic features, how they develop, and how they are linked to other senescent phenotypes, such as enlarged cell volume, increased granularity, and oxidative stress, is not clear. We investigated the potential roles of glycogen synthase kinase 3 (GSK3), a multifunctional kinase, in the development of the metabolic phenotypes in cell senescence. The inactivation of GSK3 via phosphorylation is commonly observed in diverse cell senescences. Furthermore, subcytotoxic concentration of GSK3 inhibitor was sufficient to induce cellular senescence, accompanied by augmented anabolism, such as enhanced protein synthesis, and increased glycogenesis and lipogenesis, in addition to mitochondrial dysfunction. Anabolism was accomplished through glycogen synthase, eIF2B, and SREBP1. These metabolic features seem to contribute to an increase in cellular mass by increasing glycogen granules, protein mass, and organelles. Taken together, our results suggest that GSK3 is one of the key modulators of metabolic alteration, leading the cells to senescence.

The importance of anabolism in microbial control over soil carbon storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Chao; Schimel, Joshua P.; Jastrow, Julie D.

Studies of the decomposition, transformation and stabilization of soil organic matter (SOM) have dramatically increased in recent years owing to growing interest in studying the global carbon (C) cycle as it pertains to climate change. While it is readily accepted that the magnitude of the organic C reservoir in soils depends upon microbial involvement, as soil C dynamics are ultimately the consequence of microbial growth and activity, it remains largely unknown how these microorganism-mediated processes lead to soil C stabilization. Here, we define two pathways—ex vivo modification and in vivo turnover—which jointly explain soil C dynamics driven by microbial catabolismmore » and/or anabolism. Accordingly, we use the conceptual framework of the soil ‘microbial carbon pump’ (MCP) to demonstrate how microorganisms are an active player in soil C storage. The MCP couples microbial production of a set of organic compounds to their further stabilization, which we define as the entombing effect. This integration captures the cumulative long-term legacy of microbial assimilation on SOM formation, with mechanisms (whether via physical protection or a lack of activation energy due to chemical composition) that ultimately enable the entombment of microbial-derived C in soils. We propose a need for increased efforts and seek to inspire new studies that utilize the soil MCP as a conceptual guideline for improving mechanistic understandings of the contributions of soil C dynamics to the responses of the terrestrial C cycle under global change.« less

Growth Hormone and Insulin-Like Growth Factor-1.

PubMed

Nicholls, Adam R; Holt, Richard I G

2016-01-01

Human growth hormone (GH) was first isolated from the human pituitary gland in 1945 and found to promote the growth of children with hypopituitarism. Since the formation of the World Anti-Doping Association, human GH has appeared on the list of forbidden substances. There is a significant amount of anecdotal evidence that human GH is misused by athletes to enhance performance, and there have been a number of high-profile cases of GH use in professional sport. GH secretagogues (GH-Ss), which increase GH secretion, and insulin-like growth factor (IGF-1), which mediates many of the effects of GH, are also misused, although there is less evidence for this. The effectiveness of GH, IGF-1, and GH-Ss as performance-enhancing drugs remains unclear. Evidence from studies of GH use in people with hypopituitarism show several desirable outcomes, including increased lean body mass, increased strength, and increased exercise capacity. These anabolic and metabolic properties, coupled with the difficulty in detecting them, make them attractive as agents of misuse. Studies in healthy young adults have also demonstrated a performance benefit with GH and IGF-1. © 2016 S. Karger AG, Basel.

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

PubMed

Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

1992-10-01

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

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. Copyright © 2011 Wiley-Liss, Inc.

Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults.

PubMed

Timmerman, Kyle L; Lee, Jessica L; Fujita, Satoshi; Dhanani, Shaheen; Dreyer, Hans C; Fry, Christopher S; Drummond, Micah J; Sheffield-Moore, Melinda; Rasmussen, Blake B; Volpi, Elena

2010-11-01

Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin. Twelve healthy, nondiabetic older subjects (71 ± 2 years) were randomized to two groups. Subjects were studied at baseline and during local infusion in one leg of insulin alone (Control) or insulin plus sodium nitroprusside (SNP) at variable rate to double leg blood flow. We measured leg blood flow by dye dilution; muscle microvascular perfusion with contrast enhanced ultrasound; Akt/mTORC1 signaling by Western blotting; and muscle protein synthesis, amino acid, and glucose kinetics using stable isotope methodologies. There were no baseline differences between groups. Blood flow, muscle perfusion, phenylalanine delivery to the leg, and intracellular availability of phenylalanine increased significantly (P < 0.05) in SNP only. Akt phosphorylation increased in both groups but increased more in SNP (P < 0.05). Muscle protein synthesis and net balance (nmol · min(-1) · 100 ml · leg(-1)) increased significantly (P < 0.05) in SNP (synthesis, 43 ± 6 to 129 ± 25; net balance, -16 ± 3 to 26 ± 12) but not in Control (synthesis, 41 ± 10 to 53 ± 8; net balance, -17 ± 3 to -2 ± 3). Pharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic effect of insulin in older adults.

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

PubMed Central

2012-01-01

Background Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. Results Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2–5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1–7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. Conclusion Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant

Analysis of anabolic androgenic steroids in urine by full-capillary sample injection combined with a sweeping CE stacking method.

PubMed

Wang, Chun-Chi; Cheng, Shu-Fang; Cheng, Hui-Ling; Chen, Yen-Ling

2013-02-01

This study describes an on-line stacking CE approach by sweeping with whole capillary sample filling for analyzing five anabolic androgenic steroids in urine samples. The five anabolic steroids for detection were androstenedione, testosterone, epitestosterone, boldenone, and clostebol. Anabolic androgenic steroids are abused in sport doping because they can promote muscle growth. Therefore, a sensitive detection method is imperatively required for monitoring the urine samples of athletes. In this research, an interesting and reliable stacking capillary electrophoresis method was established for analysis of anabolic steroids in urine. After liquid-liquid extraction by n-hexane, the supernatant was dried and reconstituted with 30 mM phosphate buffer (pH 5.00) and loaded into the capillary by hydrodynamic injection (10 psi, 99.9 s). The stacking and separation were simultaneously accomplished at -20 kV in phosphate buffer (30 mM, pH 5.0) containing 100 mM sodium dodecyl sulfate and 40 % methanol. During the method validation, calibration curves were linear (r≥0.990) over a range of 50-1,000 ng/mL for the five analytes. In the evaluation of precision and accuracy for this method, the absolute values of the RSD and the RE in the intra-day (n=3) and inter-day (n=5) analyses were all less than 6.6 %. The limit of detection for the five analytes was 30 ng/mL (S/N=5, sampling 99.9 s at 10 psi). Compared with simple MECK, this stacking method possessed a 108- to 175-fold increase in sensitivity. This simple and sensitive stacking method could be used as a powerful tool for monitoring the illegal use of doping.

Accentuated Osteoclastic Response to Parathyroid Hormone Undermines Bone Mass Acquisition in Osteonectin-null Mice

PubMed Central

do Reis, Luciene Machado; Kessler, Catherine B.; Adams, Douglas J.; Lorenzo, Joseph; Jorgetti, Vanda; Delany, Anne M.

2008-01-01

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone. In the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 μg/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin

Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters

PubMed Central

Salas-Ramirez, Kaliris Y.; Montalto, Pamela R.; Sisk, Cheryl L.

2010-01-01

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. PMID:18201704

21 CFR 862.1185 - Compound S (11-deoxycortisol) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...-dioxycortisol) test system is a device intended to measure the level of compound S (11-dioxycortisol) in plasma. Compound S is a steroid intermediate in the biosynthesis of the adrenal hormone cortisol. Measurements of...

Supercritical fluid chromatography applied to the highly selective isolation of urinary steroid hormones prior to GC/MS analysis.

PubMed

Doué, Mickael; West, Caroline; Bichon, Emmanuelle; Le Bizec, Bruno; Lesellier, Eric

2018-06-01

To assess the presence of prohibited anabolic substances used to promote growth in livestock, calf urine is the most relevant matrix. However, the sample preparation methods (required to remove unwanted matrix components and fractionate isobaric species that may be unresolved by gas chromatography- mass spectrometry GC/MS) are long and complex. In this context, semi-preparative supercritical fluid chromatography (SFC) was considered to possibly simplify the sample preparation in reducing the number of procedures. Fifteen stationary phases were screened with SFC combined with UV and evaporative light-scattering detection (ELSD), among which two columns (Cosmosil π-NAP and Princeton DIOL) were retained for their ability to isolate steroid hormones from other matrix components and, for the second column, for the additional possibility to fractionate steroid hormones into different families (estrogens, mono-hydroxylated and di-hydroxylated androgens). The fractions were further analysed with GC/MS showing the benefit of class fractionation. The final method allows for significant time, solvent and money savings compared to the previously widely used method (solid-phase extraction combined with semi-preparative high-performance liquid chromatography). Copyright © 2018 Elsevier B.V. All rights reserved.

Anabolic-Androgenic Steroids: Prevalence, Knowledge, and Attitudes in Junior and Senior High School Students.

ERIC Educational Resources Information Center

Luetkemeier, Maurie J.; And Others

1995-01-01

Reports a survey of junior and senior high school students that investigated the prevalence of anabolic-androgenic steroid use and examined gender, sports participation, and illicit drug use. Results indicated the prevalence of steroid use was 3.3%. Steroid use was greater for males, users of other drugs, and strength trainers. (SM)

Examining Athletes' Attitudes toward Using Anabolic Steroids and Their Knowledge of the Possible Effects.

ERIC Educational Resources Information Center

Anshel, Mark H.; Russell, Kenneth G.

1997-01-01

Examined the relationships between athletes' (N=291) knowledge about the long-term effects of anabolic steroids and their attitudes toward this type of drug. Results show low correlation between greater knowledge and attitudes about the use of steroids in sports, suggesting that drug education programs regarding steroids may have limited value.…

Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

NASA Technical Reports Server (NTRS)

Judex, Stefan; Donahue, Leah-Rae; Rubin, Clinton

2002-01-01

The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

Hormones and endocrine disruptors in human seminal plasma.

PubMed

Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

2013-07-01

Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

Effects of Growth Hormone and Nutritional Therapy in Boys with Constitutional Growth Delay: A Randomized Controlled Trial

PubMed Central

Han, Joan C.; Damaso, Ligeia; Welch, Susan; Balagopal, Prabhakaran; Hossain, Jobayer; Mauras, Nelly

2010-01-01

Objective To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). Study design We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age 9.3±1.3y) with CDGM (height-SDS -2.0±0.5, bone age delay 1.8±0.8y, BMI-SDS -1.2±1.0, peak stimulated GH 15.7±7.7ng/mL), who were randomized (N=10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. T-tests and repeated measures ANOVAs compared energy intake, total energy expenditure (TEE), growth, hormones and nutrition markers. Results Energy intake was increased at 6 months within the Nutrition (p=0.04) but not the Observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/Nutrition group at 12 months (p<0.01), but not in the GH group vs. baseline. Height, weight, lean body mass, hormones and nutrition markers increased comparably in both groups throughout 18 months. Conclusions Boys with CDGM utilize energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients. PMID:20961566

Compounds of emerging concern in the San Antonio River Basin, Texas, 2011–12

USGS Publications Warehouse

Lambert, Rebecca B.; Opsahl, Stephen P.

2016-11-16

The City of San Antonio and the surrounding municipalities in Bexar County, Texas, are among the fastest growing cities in the Nation. Increases in residential and commercial development are changing runoff patterns and likely will increase chemical loads into streams. The U.S. Geological Survey, in cooperation with the San Antonio River Authority, evaluated the concentrations and distributional patterns of selected “compounds of emerging concern” (CECs) by collecting and analyzing water-quality samples from 20 sites in the San Antonio River Basin, Tex., during 2011–12. On the basis of their chemical composition or similar uses, the CECs discussed in this fact sheet are wastewater compounds, pharmaceutical compounds (hereinafter referred to as “pharmaceuticals”), and steroidal hormone and sterol compounds (hereinafter referred to as “steroidal hormones and sterols”). Three synoptic sampling events were completed during 2011–12 to analyze for CECs in the San Antonio River Basin. Samples were analyzed for 54 wastewater compounds, 13 pharmaceuticals, 17 steroidal hormones, and 4 sterols. Overall, the concentrations of all CECs analyzed for during this study were low, generally close to or less than the laboratory reporting level.

Compound deficiencies in multiple fibroblast growth factor signalling components differentially impact the murine gonadotrophin-releasing hormone system.

PubMed

Chung, W C J; Matthews, T A; Tata, B K; Tsai, P-S

2010-08-01

Gonadotrophin-releasing hormone (GnRH) neurones control the onset and maintenance of fertility. Aberrant development of the GnRH system underlies infertility in Kallmann syndrome [KS; idiopathic hypogonadotropic hypogonadism (IHH) and anosmia]. Some KS patients harbour mutations in the fibroblast growth factor receptor 1 (Fgfr1) and Fgf8 genes. The biological significance of these two genes in GnRH neuronal development was corroborated by the observation that GnRH neurones were severely reduced in newborn transgenic mice deficient in either gene. In the present study, we hypothesised that the compound deficiency of Fgf8 and its cognate receptors, Fgfr1 and Fgfr3, may lead to more deleterious effects on the GnRH system, thereby resulting in a more severe reproductive phenotype in patients harbouring these mutations. This hypothesis was tested by counting the number of GnRH neurones in adult transgenic mice with digenic heterozygous mutations in Fgfr1/Fgf8, Fgfr3/Fgf8 or Fgfr1/Fgfr3. Monogenic heterozygous mutations in Fgfr1, Fgf8 or Fgfr3 caused a 30-50% decrease in the total number of GnRH neurones. Interestingly, mice with digenic mutations in Fgfr1/Fgf8 showed a greater decrease in GnRH neurones compared to mice with a heterozygous defect in the Fgfr1 or Fgf8 alone. This compounding effect was not detected in mice with digenic heterozygous mutations in Fgfr3/Fgf8 or Fgfr1/Fgfr3. These results support the hypothesis that IHH/KS patients with digenic mutations in Fgfr1/Fgf8 may have a further reduction in the GnRH neuronal population compared to patients harbouring monogenic haploid mutations in Fgfr1 or Fgf8. Because only Fgfr1/Fgf8 compound deficiency leads to greater GnRH system defect, this also suggests that these fibroblast growth factor signalling components interact in a highly specific fashion to support GnRH neuronal development.

Recombinant follicle-stimulating hormone: new biotechnology for infertility.

PubMed

Prevost, R R

1998-01-01

The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

PubMed Central

Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

2012-01-01

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

ANABOLIC ANDROGENIC STEROID ABUSE: MULTIPLE MECHANISMS OF REGULATION OF GABAERGIC SYNAPSES IN NEUROENDOCRINE CONTROL REGIONS OF THE RODENT FOREBRAIN

PubMed Central

Oberlander, Joseph G.; Porter, Donna M.; Penatti, Carlos A. A.; Henderson, Leslie P.

2011-01-01

Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone originally developed for clinical purposes, but now predominantly taken at suprapharmacological levels as drugs of abuse. To date, nearly 100 different AAS compounds that vary in metabolic fate and physiological effects have been designed and synthesised. While administered for their ability to enhance muscle mass and performance, untoward side effects of AAS use include changes in reproductive and sexual behaviours. Specifically, AAS, depending on the type of compound administered, can delay or advance pubertal onset, lead to irregular oestrous cyclicity, diminished male and female sexual behaviours, and accelerate reproductive senescence. Numerous brains regions and neurotransmitter signalling systems are involved in the generation of these behaviours, and are potential targets for both chronic and acute actions of the AAS. However critical to all of these behaviours is neurotransmission mediated by GABAA receptors within a nexus of interconnected forebrain regions that includes the medial preoptic area (mPOA), the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus of the hypothalamus. Here we review how exposure to AAS alters GABAergic transmission and neural activity within these forebrain regions, taking advantage of in vitro systems and both wild-type and genetically altered mouse strains, in order to better understand how these synthetic steroids affect the neural systems that underlie the regulation of reproduction and the expression of sexual behaviours. PMID:21554430

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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders.

PubMed

Blum, Werner; Alherbish, Abdullah; Alsagheir, Afaf; El Awwa, Ahmed; Kaplan, Walid; Koledova, Ekaterina; Savage, Martin O

2018-05-03

The growth hormone (GH)-insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGFBP-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

PubMed

Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

2014-08-01

Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view.

PubMed

Bifari, Francesco; Nisoli, Enzo

2017-06-01

Substantial evidence has been accumulated suggesting that branched-chain amino acid (BCAA) supplementation or BCAA-rich diets have a positive effect on the regulation of body weight, muscle protein synthesis, glucose homeostasis, the ageing process and extend healthspan. Despite these beneficial effects, epidemiological studies have shown that BCAA plasma concentrations and BCAA metabolism are altered in several metabolic disorders, including type 2 diabetes mellitus and cardiovascular diseases. In this review article, we present an overview of the current literature on the different effects of BCAAs in health and disease. We also highlight the results showing the most promising therapeutic effects of dietary BCAA supplementation and discuss how BCAAs can trigger different and even opposite effects, depending on the catabolic and anabolic states of the organisms. Moreover, we consider the effects of BCAAs when metabolism is abnormal, in the presence of a mixture of different anabolic and catabolic signals. These unique pharmacodynamic properties may partially explain some of the markedly different effects found in BCAA supplementation studies. To predict accurately these effects, the overall catabolic/anabolic status of patients should be carefully considered. In wider terms, a correct modulation of metabolic disorders would make nutraceutical interventions with BCAAs more effective. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

Branched‐chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view

PubMed Central

Bifari, Francesco

2016-01-01

Substantial evidence has been accumulated suggesting that branched‐chain amino acid (BCAA) supplementation or BCAA‐rich diets have a positive effect on the regulation of body weight, muscle protein synthesis, glucose homeostasis, the ageing process and extend healthspan. Despite these beneficial effects, epidemiological studies have shown that BCAA plasma concentrations and BCAA metabolism are altered in several metabolic disorders, including type 2 diabetes mellitus and cardiovascular diseases. In this review article, we present an overview of the current literature on the different effects of BCAAs in health and disease. We also highlight the results showing the most promising therapeutic effects of dietary BCAA supplementation and discuss how BCAAs can trigger different and even opposite effects, depending on the catabolic and anabolic states of the organisms. Moreover, we consider the effects of BCAAs when metabolism is abnormal, in the presence of a mixture of different anabolic and catabolic signals. These unique pharmacodynamic properties may partially explain some of the markedly different effects found in BCAA supplementation studies. To predict accurately these effects, the overall catabolic/anabolic status of patients should be carefully considered. In wider terms, a correct modulation of metabolic disorders would make nutraceutical interventions with BCAAs more effective. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27638647

Gender, sex hormones and pulmonary hypertension

PubMed Central

Austin, Eric D.; Lahm, Tim; West, James; Tofovic, Stevan P.; Johansen, Anne Katrine; MacLean, Margaret R.; Alzoubi, Abdallah; Oka, Masahiko

2013-01-01

Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this “estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent progress has begun to shed light upon the interplay of sex hormones, the pathogenesis of pulmonary hypertension, and the right ventricular response to stress. For example, emerging data in humans and experimental models suggest that estrogens or differential sex hormone metabolism may modify disease risk among susceptible subjects, and that estrogens may interact with additional local factors such as serotonin to enhance the potentially damaging chronic effects of estrogens on the pulmonary vasculature. Regardless, it remains unclear why not all estrogenic compounds behave equally, nor why estrogens appear to be protective in certain settings but detrimental in others. The contribution of androgens and other compounds, such as dehydroepiandrosterone, to pathogenesis and possibly treatment must be considered as well. In this review, we will discuss the recent understandings on how estrogens, estrogen metabolism, dehydroepiandrosterone, and additional susceptibility factors may all contribute to the pathogenesis or potentially to the treatment of pulmonary hypertension, by evaluating current human, cell-based, and experimental model data. PMID:24015330

The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency.

PubMed

Peschke, Bernd; Ankersen, Michael; Bauer, Michael; Hansen, Thomas Kruse; Hansen, Birgit Sehested; Nielsen, Karin Kramer; Raun, Kirsten; Richter, Lutz; Westergaard, Lisbet

2002-06-01

In order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substituents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC(50) values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C(max) of over 40 ng mL(-1).

[Plant hormones, plant growth regulators].

PubMed

Végvári, György; Vidéki, Edina

2014-06-29

Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life.

Liquid chromatography and supercritical fluid chromatography as alternative techniques to gas chromatography for the rapid screening of anabolic agents in urine.

PubMed

Desfontaine, Vincent; Nováková, Lucie; Ponzetto, Federico; Nicoli, Raul; Saugy, Martial; Veuthey, Jean-Luc; Guillarme, Davy

2016-06-17

This work describes the development of two methods involving supported liquid extraction (SLE) sample treatment followed by ultra-high performance liquid chromatography or ultra-high performance supercritical fluid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS and UHPSFC-MS/MS) for the screening of 43 anabolic agents in human urine. After evaluating different stationary phases, a polar-embedded C18 and a diol columns were selected for UHPLC-MS/MS and UHPSFC-MS/MS, respectively. Sample preparation, mobile phases and MS conditions were also finely tuned to achieve highest selectivity, chromatographic resolution and sensitivity. Then, the performance of these two methods was compared to the reference routine procedure for steroid analyses in anti-doping laboratories, which combines liquid-liquid extraction (LLE) followed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). For this purpose, urine samples spiked with the compounds of interest at five different concentrations were analyzed using the three analytical platforms. The retention and selectivity of the three techniques were very different, ensuring a good complementarity. However, the two new methods displayed numerous advantages. The overall procedure was much faster thanks to high throughput SLE sample treatment using 48-well plates and faster chromatographic analysis. Moreover, the highest sensitivity was attained using UHPLC-MS/MS with 98% of the doping agents detected at the lowest concentration level (0.1ng/mL), against 76% for UHPSFC-MS/MS and only 14% for GC-MS/MS. Finally, the weakest matrix effects were obtained with UHPSFC-MS/MS with 76% of the analytes displaying relative matrix effect between -20 and 20%, while the GC-MS/MS reference method displayed very strong matrix effects (over 100%) for all of the anabolic agents. Copyright © 2016 Elsevier B.V. All rights reserved.

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: ...

Growth hormone stimulates protein synthesis during hypocaloric parenteral nutrition. Role of hormonal-substrate environment.

PubMed Central

Manson, J M; Smith, R J; Wilmore, D W

1988-01-01

The influence of growth hormone (GH) on protein metabolism and fuel utilization was investigated in eight paired studies of normal volunteers. GH (10 mg) was given daily during one period, and saline was injected during control studies. For 6 days, subjects received parenteral nutrition that provided adequate dietary nitrogen, vitamin, and minerals, but energy intake varied to provide 30-100% of requirements. On Day 7, the feedings were discontinued and an oral glucose load (100 g) was administered. The level of energy intake did not markedly influence the actions of GH. During nutrient infusions, GH caused positive nitrogen balance (1.0 +/- 0.3 g/m2/day vs. -1.2 +/- 0.3 in controls, p less than 0.001) and increased protein synthesis (16.8 +/- 0.7 g N/m2/day vs. 13.9 +/- 0.8, p less than 0.01). No change in the rate of protein breakdown or excretion of 3-methylhistidine occurred. GH was associated with an increase in insulin and insulin-like growth factor-I concentrations (IGF-I, 9.1 +/- 0.6 IU/ml vs. 3.3 +/- 0.5, p less than 0.001). After discontinuation of the parenteral nutrition and administration of the oral glucose load, glucose concentrations tended to be higher after GH; however, despite a two- to threefold increase in insulin response, muscle glucose uptake was attenuated (1.10 +/- 0.19 g/kg forearm vs. 1.64 +/- 0.30 in controls, p less than 0.05). Compared with control conditions, GH appeared to attenuate the increase in amino acid nitrogen efflux from muscle after the administration of oral glucose. These data demonstrate that the protein anabolic effect of GH, which occurs even during hypocaloric feedings, is related to multiple mechanisms that favor protein synthesis. These include the increase in plasma concentrations of GH, insulin IGF-I and fat utilization. GH administration results in a hormonal-substrate environment that favors nitrogen retention and protein synthesis. GH may be beneficial in promoting protein synthesis in surgical patients

POSSIBLE MECHANISMS OF THYROID HORMONE DISRUPTION IN MICE BY BDE 47, A MAJOR POLYBROMINATED DIPHENYL ETHER CONGENER

EPA Science Inventory

ABSTRACT Polybromindated diphenyl ethers (PBDEs) are a class of polyhalogenated aromatic compounds commercially used as fire retardants in consumer products. These compounds have been shown to decrease thyroid hormone concentrations in rodents after acute exposures. Based on t...

Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone?

PubMed

Havekes, Bas; Sauerwein, Hans P

2010-11-01

To review original research studies and reviews that present data on adipocyte-myocyte crosstalk in the development of skeletal muscle insulin resistance with a specific focus on thyroid hormone. Adipose tissue communicates with skeletal muscle not only through free fatty acids but also through secretion of various products called adipokines. Adipokines came out as governors of insulin sensitivity and are deregulated in obesity. In addition to well known leptin, adiponectin, interleukin-6 and tumor necrosis factor-alpha, newer adipokines like retinol-binding protein 4 have been associated with insulin resistance. There is mounting evidence that not only adipose tissue but also skeletal muscle produces and secretes biologically active proteins or 'myokines' that facilitate metabolic crosstalk between organ systems. In recent years, increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Both hypothyroidism and hyperthyroidism affect insulin sensitivity in multiple ways that might overlap adipocyte-myocyte crosstalk. Recent studies have provided new insights in effects of processing of the parent hormone T4 to the active T3 at the level of the skeletal muscle. Adipocyte-myocyte crosstalk is an important modulator in the development of skeletal muscle insulin resistance. Thyroid disorders are very common and may have detrimental effects on skeletal muscle insulin resistance, potentially by interacting with adipocyte-myocyte crosstalk.

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

PubMed Central

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-01-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells. PMID:2548207

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

PubMed

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

TRICLOSAN ALTERS THYROID HORMONES HOMEOSTASIS VIA UP-REGULATION OF HEPATIC CATABOLISM.

EPA Science Inventory

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is a chlorinated phenolic antibacterial compound used in household and hygiene products. The structural similarity of triclosan to thyroid hormones, in vitro studies demonstrating activation of the human pregnane X receptor (PXR)...

TRICLOSAN AND ENDOCRINE DISRUPTION: EVIDENCE FOR ALTERATIONS IN THYROID HORMONE HOMEOSTASIS.

EPA Science Inventory

Impact Statement: Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is a chlorinated phenolic antibacterial compound found as an active ingredient in many personal care and household products. Recent studies suggest that triclosan may alter thyroid hormone (TH) homeostasis via ...

The "yin and yang" of the adrenal and gonadal systems in elite military men.

PubMed

Taylor, Marcus K; Hernández, Lisa M; Kviatkovsky, Shiloah A; Schoenherr, Matthew R; Stone, Michael S; Sargent, Paul

2017-05-01

We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the "positive coupling" hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the "yin and yang" of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.

Insulin-like growth factor 1 (IGF-1): a growth hormone

PubMed Central

Laron, Z

2001-01-01

Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173

The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats.

PubMed

Vargas, Rafael Arêas; Oliveira, Leonardo Pires; Frankenfeld, Stephan; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Favorito, Luciano Alves; Sampaio, Francisco José Barcellos

2013-01-01

Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p < 0.05 was considered significant). The weight (p < 0.001) and volume (p = 0.004) of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509), but the T105 group showed an increase of 32% compared to C105 (p = 0.0089). Concerning the lumen, surface density presented no

Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists.

PubMed

Yanofsky, Stephen D; Shen, Emily S; Holden, Frank; Whitehorn, Erik; Aguilar, Barbara; Tate, Emily; Holmes, Christopher P; Scheuerman, Randall; MacLean, Derek; Wu, May M; Frail, Donald E; López, Francisco J; Winneker, Richard; Arey, Brian J; Barrett, Ronald W

2006-05-12

The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 microm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.

Long-Term Anabolic Androgenic Steroid Use Is Associated with Increased Atrial Electromechanical Delay in Male Bodybuilders

PubMed Central

Akçakoyun, Mustafa; Gündoğdu, Recep; Bulut, Mustafa; Tabakcı, Mehmet Mustafa; Açar, Göksel; Avcı, Anıl; Şimşek, Zeki; Demir, Serdar; Kargın, Ramazan; Emiroğlu, Mehmet Yunus

2014-01-01

We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids (AAS) on atrial electromechanical delay (AEMD) in male bodybuilders. We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders. PMID:24883314

Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc.

PubMed

Kim, Jae-Sung; Ellman, Michael B; An, Howard S; Yan, Dongyao; van Wijnen, Andre J; Murphy, Gillian; Hoskin, David W; Im, Hee-Jeong

2012-04-01

Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated catabolic enzymes. LfcinB's anti-catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future. Copyright © 2011 Wiley Periodicals, Inc.

The effect of HMB supplementation on body composition, fitness, hormonal and inflammatory mediators in elite adolescent volleyball players: a prospective randomized, double-blind, placebo-controlled study.

PubMed

Portal, Shawn; Zadik, Zvi; Rabinowitz, Jonathan; Pilz-Burstein, Ruty; Adler-Portal, Dana; Meckel, Yoav; Cooper, Dan M; Eliakim, Alon; Nemet, Dan

2011-09-01

The use of ergogenic nutritional supplements is becoming inseparable from competitive sports. β-Hydroxy-β-Methylbutyric acid (HMB) has recently been suggested to promote fat-free mass (FFM) and strength gains during resistance training in adults. In this prospective randomized, double-blind, placebo-controlled study, we studied the effect of HMB (3 g/day) supplementation on body composition, muscle strength, anaerobic and aerobic capacity, anabolic/catabolic hormones and inflammatory mediators in elite, national team level adolescent volleyball players (13.5-18 years, 14 males, 14 females, Tanner stage 4-5) during the first 7 weeks of the training season. HMB led to a significant greater increase in FFM by skinfold thickness (56.4 ± 10.2 to 56.3 ± 8.6 vs. 59.3 ± 11.3 to 61.6 ± 11.3 kg in the control and HMB group, respectively, p < 0.001). HMB led to a significant greater increase in both dominant and non-dominant knee flexion isokinetic force/FFM, measured at fast (180°/sec) and slow (60°/sec) angle speeds, but had no significant effect on knee extension and elbow flexion and extension. HMB led to a significant greater increase in peak and mean anaerobic power determined by the Wingate anaerobic test (peak power: 15.5 ± 1.6 to 16.2 ± 1.2 vs. 15.4 ± 1.6 to 17.2 ± 1.2 watts/FFM, mean power: 10.6 ± 0.9 to 10.8 ± 1.1 vs. 10.7 ± 0.8 to 11.8 ± 1.0 watts/FFM in control and HMB group, respectively, p < 0.01), with no effect on fatigue index. HMB had no significant effect on aerobic fitness or on anabolic (growth hormone, IGF-I, testosterone), catabolic (cortisol) and inflammatory mediators (IL-6 and IL-1 receptor antagonist). HMB supplementation was associated with greater increases in muscle mass, muscle strength and anaerobic properties with no effect on aerobic capacity suggesting some advantage for its use in elite adolescent volleyball players during the initial phases of the training season. These effects were not accompanied by hormonal and

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.

Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

PubMed

Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

2004-02-12

A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

Design, Synthesis, and Biological Characterization of Metabolically Stable Selective Androgen Receptor Modulators

PubMed Central

Marhefka, Craig A.; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T.; Miller, Duane D.

2007-01-01

A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with Ki values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo. PMID:14761201

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 cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

Parathyroid hormone and its analogues--molecular mechanisms of action and efficacy in osteoporosis therapy.

PubMed

Misiorowski, Waldemar

2011-01-01

Most medical agents currently applied in osteoporosis therapy act by inhibiting bone resorption and reducing bone remodelling, i.e. they inhibit the process of bone mass loss by suppressing bone resorption processes. These drugs provide an ideal therapeutic option to prevent osteoporosis progression. They however have a rather limited usefulness when the disease has already reached its advanced stages with distinctive bone architecture lesions. The fracture risk reduction rate, achieved in the course of anti-resorptive therapy, is insufficient for patients with severe osteoporosis to stop the downward spiral of their quality of life (QoL) with a simultaneously increasing threat of premature death. The activity of the N-terminal fragment of 1-34 human parathormone (teriparatide - 1-34 rhPTH), a parathyroid hormone (PTH) analogue obtained via genetic engineering , is expressed by increased bone metabolism, while promoting new bone tissue formation by stimulating the activity of osteoblasts more than that of osteoclasts. The anabolic activity of PTH includes both its direct effect on the osteoblast cell line, and its indirect actions exerted via its regulatory effects on selected growth factors, e.g. IGF-1 or sclerostin. However, the molecular mechanisms responsible for the actual anabolic effects of PTH remain mostly still unclear. Clinical studies have demonstrated that therapeutic protocols with the application of PTH analogues provide an effective protection against all osteoporotic fracture types in post-menopausal women and in elderly men with advanced osteoporosis. Particular hopes are pinned on the possibility of applying PTH in the therapy of post-steroid osteoporosis, mainly to suppress bone formation, the most important pathological process in this regard. The relatively short therapy period with a PTH analogue (24 months) should then be replaced and continued by anti-resorptive treatment.

[Parathyroid hormone and its analogues - molecular mechanisms of action and efficacy of osteoporosis therapy].

PubMed

Misiorowski, Waldemar

2011-01-01

Most medical agents currently applied in osteoporosis therapy act by inhibiting bone resorption and reducing bone remodelling, i.e. they inhibit the process of bone mass loss by suppressing bone resorption processes. These drugs provide an ideal therapeutic option to prevent osteoporosis progression. They however have a rather limited usefulness when the disease has already reached its advanced stages with distinctive bone architecture lesions. The fracture risk reduction rate, achieved in the course of anti-resorptive therapy, is insufficient for patients with severe osteoporosis to stop the downward spiral of their quality of life (QoL) with a simultaneously increasing threat of premature death. The activity of the N-terminal fragment of 1-34 human parathormone (teriparatide - 1-34 rhPTH), a parathyroid hormone (PTH) analogue obtained via genetic engineering , is expressed by increased bone metabolism, while promoting new bone tissue formation by stimulating the activity of osteoblasts more than that of osteoclasts. The anabolic activity of PTH includes both its direct effect on the osteoblast cell line, and its indirect actions exerted via its regulatory effects on selected growth factors, e.g. IGF-1 or sclerostin. However, the molecular mechanisms responsible for the actual anabolic effects of PTH remain mostly still unclear. Clinical studies have demonstrated that therapeutic protocols with the application of PTH analogues provide an effective protection against all osteoporotic fracture types in post-menopausal women and in elderly men with advanced osteoporosis. Particular hopes are pinned on the possibility of applying PTH in the therapy of post-steroid osteoporosis, mainly to suppress bone formation, the most important pathological process in this regard. The relatively short therapy period with a PTH analogue (24 months) should then be replaced and continued by anti-resorptive treatment.

Discovering potential Streptomyces hormone producers by using disruptants of essential biosynthetic genes as indicator strains.

PubMed

Thao, Nguyen B; Kitani, Shigeru; Nitta, Hiroko; Tomioka, Toshiya; Nihira, Takuya

2017-10-01

Autoregulators are low-molecular-weight signaling compounds that control the production of many secondary metabolites in actinomycetes and have been referred to as 'Streptomyces hormones'. Here, potential producers of Streptomyces hormones were investigated in 40 Streptomyces and 11 endophytic actinomycetes. Production of γ-butyrolactone-type (IM-2, VB) and butenolide-type (avenolide) Streptomyces hormones was screened using Streptomyces lavendulae FRI-5 (ΔfarX), Streptomyces virginiae (ΔbarX) and Streptomyces avermitilis (Δaco), respectively. In these strains, essential biosynthetic genes for Streptomyces hormones were disrupted, enabling them to respond solely to the externally added hormones. The results showed that 20% of each of the investigated strains produced IM-2 and VB, confirming that γ-butyrolactone-type Streptomyces hormones are the most common in actinomycetes. Unlike the γ-butyrolactone type, butenolide-type Streptomyces hormones have been discovered in recent years, but their distribution has been unclear. Our finding that 24% of actinomycetes (12 of 51 strains) showed avenolide activity revealed for the first time that the butenolide-type Streptomyces hormone is also common in actinomycetes.

Chronic Exposure to Anabolic Androgenic Steroids Alters Activity and Synaptic Function in Neuroendocrine Control Regions of the Female Mouse

PubMed Central

Penatti, Carlos A.A.; Oberlander, Joseph G.; Davis, Matthew C.; Porter, Donna M.; Henderson, Leslie P.

2011-01-01

Summary Disruption of reproductive function is a hallmark of abuse of anabolic androgenic steroids (AAS) in female subjects. To understand the central actions of AAS, patch clamp recordings were made in estrous, diestrous and AAS-treated mice from gonadotropin releasing hormone (GnRH) neurons, neurons in the medial preoptic area (mPOA) and neurons in the anteroventroperiventricular nucleus (AVPV); regions known to provide GABAergic and kisspeptin inputs to the GnRH cells. Action potential (AP) frequency was significantly higher in GnRH neurons of estrous mice than in AAS-treated or diestrous animals. No significant differences in AAS-treated, estrous or diestrous mice were evident in the amplitude or kinetics of spontaneous postsynaptic currents (sPCSs), miniature PSCs or tonic currents mediated by GABAA receptors or in GABAA receptor subunit expression in GnRH neurons. In contrast, the frequency of GABAA receptor-mediated sPSCs in GnRH neurons showed an inverse correlation with AP frequency across the three hormonal states. Surprisingly, AP activity in the medial preoptic area (mPOA), a likely source of GABAergic afferents to GnRH cells, did not vary in concert with the sPSCs in the GnRH neurons. Furthermore, pharmacological blockade of GABAA receptors did not alter the pattern in which there was lower AP frequency in GnRH neurons of AAS-treated and diestrous versus estrous mice. These data suggest that AAS do not impose their effects either directly on GnRH neurons or on putative GABAergic afferents in the mPOA. AP activity recorded from neurons in kisspeptin-rich regions of the anteroventroperiventricular nucleus (AVPV) and the expression of kisspeptin mRNA and peptide did vary coordinately with AP activity in GnRH neurons. Our data demonstrate that AAS treatment imposes a “diestrous-like” pattern of activity in GnRH neurons and suggest that this effect may arise from suppression of presynaptic kisspeptin-mediated excitatory drive arising from the AVPV. The

Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis.

PubMed

Ding, Qingfeng; Sun, Peng; Zhou, Hao; Wan, Bowen; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Fan, Jin

2018-07-01

Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated. Fracture healing was observed using X‑ray and micro‑computerized tomography. Bone anabolic and angiogenic markers were analyzed by immunohistochemistry and western blot analysis. The expression levels of VEGF and associated signaling pathways in murine BMSC‑derived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylated‑serine/threonine protein kinase (pAKT), hypoxia‑inducible factor‑1α (HIF1α) and VEGF were significantly decreased in BMSC‑derived osteoblasts from PTHKO mice. In addition, positive platelet endothelial cell adhesion molecule staining was reduced in PTHKO mice, as determined by immunohistochemistry. The expression levels of HIF1α, VEGF, runt‑related transcription factor 2, osteocalcin and alkaline phosphatase were also decreased in PTHKO mice, and fracture healing was delayed. In conclusion, lack of endogenous PTH may reduce VEGF expression in BMSC‑derived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1α/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing.

Combined sewer overflows: an environmental source of hormones and wastewater micropollutants

USGS Publications Warehouse

Phillips, P.J.; Chalmers, A.T.; Gray, J.L.; Kolpin, D.W.; Foreman, W.T.; Wall, G.R.

2012-01-01

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40–90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency.

Combined Sewer Overflows: An Environmental Source of Hormones and Wastewater Micropollutants

PubMed Central

2012-01-01

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40–90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency. PMID:22540536

Sepsis attenuates the anabolic response to skeletal muscle contraction

PubMed Central

Steiner, Jennifer L.; Lang, Charles H.

2014-01-01

Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ~24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the non-stimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 substrates S6K1 Thr389 (8-fold), S6K1 Thr421/Ser424 (7-fold) and 4E-BP1 Ser65 (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr389 (67%), S6K1 Thr421/Ser424 (46%) and 4E-BP1 Ser65 (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr56 phosphorylation was decreased similarly by muscle contraction in both groups. MAPK signaling was discordant following muscle contraction in septic muscle; phosphorylation of ERK Thr202/Tyr204 and p38 Thr180/Tyr182 was increased similarly in both CON and CLP mice while sepsis prevented the contraction-induced phosphorylation of JNK Thr183/Tyr185 and c-JUN Ser63. The expression of IL-6 and TNF-α mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR-mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent. PMID:25423127

Sepsis attenuates the anabolic response to skeletal muscle contraction.

PubMed

Steiner, Jennifer L; Lang, Charles H

2015-04-01

Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ∼24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor α (TNF-α) mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent.

At same leucine intake, a whey/plant protein blend is not as effective as whey to initiate a transient post prandial muscle anabolic response during a catabolic state in mini pigs.

PubMed

Revel, Aurélia; Jarzaguet, Marianne; Peyron, Marie-Agnès; Papet, Isabelle; Hafnaoui, Noureddine; Migné, Carole; Mosoni, Laurent; Polakof, Sergio; Savary-Auzeloux, Isabelle; Rémond, Didier; Dardevet, Dominique

2017-01-01

Muscle atrophy has been explained by an anabolic resistance following food intake and an increase of dietary protein intake is recommended. To be optimal, a dietary protein has to be effective not only to initiate but also to prolong a muscle anabolic response in a catabolic state. To our knowledge, whether or not a dairy or a dairy/plant protein blend fulfills these criterions is unknown in a muscle wasting situation. Our aim was, in a control and a catabolic state, to measure continuously muscle anabolism in term of intensity and duration in response to a meal containing casein (CAS), whey (WHEY) or a whey/ plant protein blend (BLEND) and to evaluate the best protein source to elicit the best post prandial anabolism according to the physio-pathological state. Adult male Yucatan mini pigs were infused with U-13C-Phenylalanine and fed either CAS, WHEY or BLEND. A catabolic state was induced by a glucocorticoid treatment for 8 days (DEX). Muscle protein synthesis, proteolysis and balance were measured with the hind limb arterio-venous differences technique. Repeated time variance analysis were used to assess significant differences. In a catabolic situation, whey proteins were able to initiate muscle anabolism which remained transient in contrast to the stimulated muscle protein accretion with WHEY, CAS or BLEND in healthy conditions. Despite the same leucine intake compared to WHEY, BLEND did not restore a positive protein balance in DEX animals. Even with WHEY, the duration of the anabolic response was not optimal and has to be improved in a catabolic state. The use of BLEND remained of lower efficiency even at same leucine intake than whey.

The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

PubMed

Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

2017-01-01

Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bajusz, S.; Janaky, T.; Csernus, V.J.

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Ofmore » the peptides prepared, (D-Mel{sup 6})LH-RH (SB-05) and (Ac-D-Nal(2){sup 1},D-Phe(pCl){sup 2},D-Pal(3){sup 3},Arg{sup 5},D-Mel{sup 6},D-Ala{sup 10})LH-RH (SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine) possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel{sup 6} analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.« less

Turnover of pigment granules: cyclic catabolism and anabolism of ommochromes within epidermal cells.

PubMed

Insausti, T C; Casas, J

2009-12-01

Ommochromes are end products of the tryptophan metabolism in arthropods. While the anabolism of ommochromes has been well studied, the catabolism is totally unknown. In order to study it, we used the crab-spider Misumena vatia, which is able to change color reversibly in a few days, from yellow to white and back. Ommochromes is the only pigment class responsible for the body coloration in this animal. The aim of this study was to analyze the fine structure of the epidermal cells in bleaching spiders, in an attempt to correlate morphological changes with the fate of the pigment granules. Central to the process of bleaching is the lysis of the ommochrome granules. In the same cell, intact granules and granules in different degradation stages are found. The degradation begins with granule autolysis. Some components are extruded in the extracellular space and others are recycled via autophagy. Abundant glycogen appears associated to granulolysis. In a later stage of bleaching, ommochrome progranules, typical of white spiders, appear in the distal zone of the same epidermal cell. Catabolism and anabolism of pigment granules thus take place simultaneously in spider epidermal cells. A cyclic pathway of pigment granules formation and degradation, throughout a complete cycle of color change is proposed, together with an explanation for this turnover, involving photoprotection against UV by ommochromes metabolites. The presence of this turnover for melanins is discussed.

Short-chain analogs of luteinizing hormone-releasing hormone containing cytotoxic moieties.

PubMed

Janáky, T; Juhász, A; Rékási, Z; Serfözö, P; Pinski, J; Bokser, L; Srkalovic, G; Milovanovic, S; Redding, T W; Halmos, G

1992-11-01

Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line.

Short-chain analogs of luteinizing hormone-releasing hormone containing cytotoxic moieties.

PubMed Central

Janáky, T; Juhász, A; Rékási, Z; Serfözö, P; Pinski, J; Bokser, L; Srkalovic, G; Milovanovic, S; Redding, T W; Halmos, G

1992-01-01

Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line. PMID:1332035

Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.

PubMed

Germanakis, Ioannis; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tsitsimpikou, Christina; Goutzourelas, Nikolaos; Champsas, Maria Christakis; Stagos, Demetrios; Rentoukas, Elias; Tsatsakis, Aristidis M

2013-11-01

The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4 months-old). The experimental scheme consisted of two oral administration periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aerobic Exercise Training Prevents Heart Failure-Induced Skeletal Muscle Atrophy by Anti-Catabolic, but Not Anabolic Actions

PubMed Central

Souza, Rodrigo W. A.; Piedade, Warlen P.; Soares, Luana C.; Souza, Paula A. T.; Aguiar, Andreo F.; Vechetti-Júnior, Ivan J.; Campos, Dijon H. S.; Fernandes, Ana A. H.; Okoshi, Katashi; Carvalho, Robson F.; Cicogna, Antonio C.; Dal-Pai-Silva, Maeli

2014-01-01

Background Heart failure (HF) is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET) in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting. Methods and Results We employed ascending aortic stenosis (AS) inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET) or to an untrained group (AS-UN). At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65), MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels. Conclusions Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state. PMID:25330387

Hormonal Interference with Pheromone Systems in Parasitic Acarines, Especially Ixodid Ticks.

DTIC Science & Technology

1984-05-01

neuro- secretory morphology of the chicken mite Dermanyssus gallinae (Mesostigmata:Dermanyssidae). J. Morphol. (in press). *12. Oliver, J.H., Jr., J.M...13. Oliver, J.H., Jr., J.M. Pound and G. Severino. Evidence of a juvenile hormone-like compound in reproduction of Dermanyssus gallinae (Acari

Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers

PubMed Central

Cojocneanu Petric, Roxana; Braicu, Cornelia; Raduly, Lajos; Zanoaga, Oana; Dragos, Nicolae; Monroig, Paloma; Dumitrascu, Dan; Berindan-Neagoe, Ioana

2015-01-01

Over the years, nutrition and environmental factors have been demonstrated to influence human health, specifically cancer. Owing to the fact that cancer is a leading cause of death worldwide, efforts are being made to elucidate molecular mechanisms that trigger or delay carcinogenesis. Phytochemicals, in particular, have been shown to modulate oncogenic processes through their antioxidant and anti-inflammatory activities and their ability to mimic the chemical structure and activity of hormones. These compounds can act not only by influencing oncogenic proteins, but also by modulating noncoding RNAs such as microRNAs and long noncoding RNAs. Although we are only beginning to understand the complete effects of many natural compounds, such as phytochemicals, researchers are motivated to combine these agents with traditional, chemo-based, or hormone-based therapies to fight against cancer. Since ongoing studies continue to prove effective, herein we exalt the importance of improving dietary choices as a chemo-preventive strategy. PMID:26273208

Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel Supernatants on Equine Synovial Membrane Explants Challenged with Lipopolysaccharide

PubMed Central

Ríos, Diana L.; Pérez, Jorge E.

2017-01-01

Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis (OA). However, some controversies remain regarding the ideal concentration of platelets and leukocytes to produce an adequate anti-inflammatory and anabolic response in the synovial membrane. The aims of this study were to study the influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some proinflammatory and anabolic genes in equine synovial membrane explants (SMEs) challenged with lipopolysaccharide (LPS). SMEs from six horses were cultured over 96 h. Then, SMEs were harvested for RNA extraction and quantitative gene expression analysis by RT-qPCR for nuclear factor kappa B (NFκB), matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen type II alpha 1 (COL2A1), and cartilage oligomeric matrix protein (COMP). The 25% and 50% Lc-PRG supernatants led to downregulation of NFκB, MMP-13, ADAMTS-4, COL1A1, COL2A1, and COMP in SMEs. Lr-PRG supernatants (particularly at the 50% concentration) induced downregulation of NFκB, MMP-13, ADAMTS-4, and COL1A1 and upregulation of COL2A1 and COMP. Lr-PRG supernatants should be used for the treatment of inflammatory arthropathies in horses because they have anti-inflammatory and anabolic effects in the synovial membrane. PMID:28761774

Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel Supernatants on Equine Synovial Membrane Explants Challenged with Lipopolysaccharide.

PubMed

Carmona, Jorge U; Ríos, Diana L; López, Catalina; Álvarez, María E; Pérez, Jorge E

2017-01-01

Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis (OA). However, some controversies remain regarding the ideal concentration of platelets and leukocytes to produce an adequate anti-inflammatory and anabolic response in the synovial membrane. The aims of this study were to study the influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some proinflammatory and anabolic genes in equine synovial membrane explants (SMEs) challenged with lipopolysaccharide (LPS). SMEs from six horses were cultured over 96 h. Then, SMEs were harvested for RNA extraction and quantitative gene expression analysis by RT-qPCR for nuclear factor kappa B (NF κ B), matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen type II alpha 1 (COL2A1), and cartilage oligomeric matrix protein (COMP). The 25% and 50% Lc-PRG supernatants led to downregulation of NF κ B, MMP-13, ADAMTS-4, COL1A1, COL2A1, and COMP in SMEs. Lr-PRG supernatants (particularly at the 50% concentration) induced downregulation of NF κ B, MMP-13, ADAMTS-4, and COL1A1 and upregulation of COL2A1 and COMP. Lr-PRG supernatants should be used for the treatment of inflammatory arthropathies in horses because they have anti-inflammatory and anabolic effects in the synovial membrane.

TR-DB: an open-access database of compounds affecting the ethylene-induced triple response in Arabidopsis.

PubMed

Hu, Yuming; Callebert, Pieter; Vandemoortel, Ilse; Nguyen, Long; Audenaert, Dominique; Verschraegen, Luc; Vandenbussche, Filip; Van Der Straeten, Dominique

2014-02-01

Small molecules which act as hormone agonists or antagonists represent useful tools in fundamental research and are widely applied in agriculture to control hormone effects. High-throughput screening of large chemical compound libraries has yielded new findings in plant biology, with possible future applications in agriculture and horticulture. To further understand ethylene biosynthesis/signaling and its crosstalk with other hormones, we screened a 12,000 compound chemical library based on an ethylene-related bioassay of dark-grown Arabidopsis thaliana (L.) Heynh. seedlings. From the initial screening, 1313 (∼11%) biologically active small molecules altering the phenotype triggered by the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), were identified. Selection and sorting in classes were based on the angle of curvature of the apical hook, the length and width of the hypocotyl and the root. A MySQL-database was constructed (https://chaos.ugent.be/WE15/) including basic chemical information on the compounds, images illustrating the phenotypes, phenotype descriptions and classification. The research perspectives for different classes of hit compounds will be evaluated, and some general screening tips for customized high-throughput screening and pitfalls will be discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.

PubMed

Loche, S; Carta, D; Muntoni, A C; Corda, R; Pintor, C

1993-10-01

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.

At same leucine intake, a whey/plant protein blend is not as effective as whey to initiate a transient post prandial muscle anabolic response during a catabolic state in mini pigs

PubMed Central

Revel, Aurélia; Jarzaguet, Marianne; Peyron, Marie-Agnès; Papet, Isabelle; Hafnaoui, Noureddine; Migné, Carole; Mosoni, Laurent; Polakof, Sergio; Savary-Auzeloux, Isabelle; Rémond, Didier

2017-01-01

Background Muscle atrophy has been explained by an anabolic resistance following food intake and an increase of dietary protein intake is recommended. To be optimal, a dietary protein has to be effective not only to initiate but also to prolong a muscle anabolic response in a catabolic state. To our knowledge, whether or not a dairy or a dairy/plant protein blend fulfills these criterions is unknown in a muscle wasting situation. Objective Our aim was, in a control and a catabolic state, to measure continuously muscle anabolism in term of intensity and duration in response to a meal containing casein (CAS), whey (WHEY) or a whey/ plant protein blend (BLEND) and to evaluate the best protein source to elicit the best post prandial anabolism according to the physio-pathological state. Methods Adult male Yucatan mini pigs were infused with U-13C-Phenylalanine and fed either CAS, WHEY or BLEND. A catabolic state was induced by a glucocorticoid treatment for 8 days (DEX). Muscle protein synthesis, proteolysis and balance were measured with the hind limb arterio-venous differences technique. Repeated time variance analysis were used to assess significant differences. Results In a catabolic situation, whey proteins were able to initiate muscle anabolism which remained transient in contrast to the stimulated muscle protein accretion with WHEY, CAS or BLEND in healthy conditions. Despite the same leucine intake compared to WHEY, BLEND did not restore a positive protein balance in DEX animals. Conclusions Even with WHEY, the duration of the anabolic response was not optimal and has to be improved in a catabolic state. The use of BLEND remained of lower efficiency even at same leucine intake than whey. PMID:29045496

Syntheses of precursors and reference compounds of the melanin-concentrating hormone receptor 1 (MCHR1) tracers [¹¹C]SNAP-7941 and [¹⁸F]FE@SNAP for positron emission tomography.

PubMed

Schirmer, Eva; Shanab, Karem; Datterl, Barbara; Neudorfer, Catharina; Mitterhauser, Markus; Wadsak, Wolfgang; Philippe, Cécile; Spreitzer, Helmut

2013-09-30

The MCH receptor has been revealed as a target of great interest in positron emission tomography imaging. The receptor's eponymous substrate melanin-concentrating hormone (MCH) is a cyclic peptide hormone, which is located predominantly in the hypothalamus with a major influence on energy and weight regulation as well as water balance and memory. Therefore, it is thought to play an important role in the pathophysiology of adiposity, which is nowadays a big issue worldwide. Based on the selective and high-affinity MCH receptor 1 antagonist SNAP-7941, a series of novel SNAP derivatives has been developed to provide different precursors and reference compounds for the radiosyntheses of the novel PET radiotracers [(11)C]SNAP-7941 and [(18)F]FE@SNAP. Positron emission tomography promotes a better understanding of physiologic parameters on a molecular level, thus giving a deeper insight into MCHR1 related processes as adiposity.

Exercise associated hormonal signals as powerful determinants of an effective fat mass loss.

PubMed

Bajer, B; Vlcek, M; Galusova, A; Imrich, R; Penesova, A

2015-07-01

Obesity management for achieving an effective weight loss includes dietary modification and exercise [resistance (strength), endurance (cardiovascular) or intervals training (high-intensity intermittent exercise)]. Regular exercise acutely increases fat oxidation, which induces loss of fat mass and increases energy expenditure. Moreover, it has a positive effect on the physical (improved insulin sensitivity, lipid profile, etc.) and mental health (mood, cognition, memory, sleep, etc.). Endocrine responses to muscle actions are affected by many factors, including the exercise muscle groups (lower and upper body), load/volume, time-under tension, and rest-period intervals between sets, training status, gender, and age. The aim of this review is to summarize, evaluate, and clarify the literature data focusing on the endocrine responses to different types of exercise, including the frequency, intensity, and type of movement with regard to the fat loss strategies. Many studies have investigated anabolic [growth hormone, insulin-like growth factor-1 (IGF-1), testosterone] and gluco- and appetite- regulatory (insulin, cortisol, ghrelin) hormone responses and adaptations of skeletal muscles to exercise. Muscle tissue is a critical endocrine organ, playing important role in the regulation of several physiological and metabolic events. Moreover, we are also describing the response of some other substances to exercise, such as myokines [irisin, apelin, brain-derived neurotrophic factor (BDNF), myostatin, and fibroblast growth factor 21 (FGF21)]. It is proposed that reducing intra-abdominal fat mass and increasing cardiorespiratory fitness through improving nutritional quality, reducing sedentary behavior, and increase the participation in physical activity/exercise, might be associated with clinical benefits, sometimes even in the absence of weight loss.

Acute hormonal responses before and after 2 weeks of HIT in well trained junior triathletes.

PubMed

Zinner, C; Wahl, P; Achtzehn, S; Reed, J L; Mester, J

2014-04-01

The aim was to compare the acute hormonal response to a single HIT session at the beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8±1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples were collected before and after the first and last HIT session. Significant increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first session +435.1%; last session +314.6%) concentrations were observed after both training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3 were not different between the first and last HIT sessions (P=1.00). Although no acute changes in testosterone were detected after the training sessions, testosterone concentrations were significantly higher at all time points (62.6-80.1%) during the last compared to first training session (P≤0.001). Findings from the present study reveal that 16 sessions of HIT led to significant increases in baseline concentrations of serum testosterone. This might indicate a heightened anabolic state even in junior triathletes. Based on the hormonal data, we conclude that at the end of this 2 week microcycle no familiarization effect was evident and that the training stimulus produced by HIT was still great enough to "stress" the athletes and induce positive training adaptations. © Georg Thieme Verlag KG Stuttgart · New York.

Mutations in PROP1 cause familial combined pituitary hormone deficiency.

PubMed

Wu, W; Cogan, J D; Pfäffle, R W; Dasen, J S; Frisch, H; O'Connell, S M; Flynn, S E; Brown, M R; Mullis, P E; Parks, J S; Phillips, J A; Rosenfeld, M G

1998-02-01

Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH) and one or more of the other five anterior pituitary hormones. Mutations of the pituitary transcription factor gene POU1F1 (the human homologue of mouse Pit1) are responsible for deficiencies of GH, prolactin and thyroid stimulating hormone (TSH) in Snell and Jackson dwarf mice and in man, while the production of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) is preserved. The Ames dwarf (df) mouse displays a similar phenotype, and appears to be epistatic to Snell and Jackson dwarfism. We have recently positionally cloned the putative Ames dwarf gene Prop1, which encodes a paired-like homeodomain protein that is expressed specifically in embryonic pituitary and is necessary for Pit1 expression. In this report, we have identified four CPHD families with homozygosity or compound heterozygosity for inactivating mutations of PROP1. These mutations in the human PROP1 gene result in a gene product with reduced DNA-binding and transcriptional activation ability in comparison to the product of the murine df mutation. In contrast to individuals with POU1F1 mutations, those with PROP1 mutations cannot produce LH and FSH at a sufficient level and do not enter puberty spontaneously. Our results identify a major cause of CPHD in humans and suggest a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.

Relationships between structure, ionization profile and sensitivity of exogenous anabolic steroids under electrospray ionization and analysis in human urine using liquid chromatography-tandem mass spectrometry.

PubMed

Cha, Eunju; Kim, Sohee; Kim, Hee Won; Lee, Kang Mi; Kim, Ho Jun; Kwon, Oh-Seung; Lee, Jaeick

2016-04-01

The relationships between the ionization profile, sensitivity, and structures of 64 exogenous anabolic steroids (groups I-IV) was investigated under electrospray ionization (ESI) conditions. The target analytes were ionized as [M + H](+) or [M + H-nH2 O](+) in the positive mode, and these ions were used as precursor ions for selected reaction monitoring analysis. The collision energy and Q3 ions were optimized based on the sensitivity and selectivity. The limits of detection (LODs) were 0.05-20 ng/mL for the 64 steroids. The LODs for 38 compounds, 14 compounds and 12 compounds were in the range of 0.05-1, 2-5 and 10-20 ng/mL, respectively. Steroids including the conjugated keto-functional group at C3 showed good proton affinity and stability, and generated the [M + H](+) ion as the most abundant precursor ion. In addition, the LODs of steroids using the [M + H](+) ion as the precursor ion were mostly distributed at low concentrations. In contrast, steroids containing conjugated/unconjugated hydroxyl functional groups at C3 generated [M + H - H2 O](+) or [M + H - 2H2 O](+) ions, and these steroids showed relatively high LODs owing to poor stability and multiple ion formation. An LC-MS/MS method based on the present ionization profile was developed and validated for the determination of 78 steroids (groups I-V) in human urine. Copyright © 2015 John Wiley & Sons, Ltd.

Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload.

PubMed

Washington, Tyrone A; Healey, Julie M; Thompson, Raymond W; Lowe, Larry L; Carson, James A

2014-09-01

Aging alters the skeletal muscle response to overload-induced growth. The onset of functional overload is characterized by increased myoblast proliferation and an altered muscle metabolic profile. The onset of functional overload is associated with increased energy demands that are met through the interconversion of lactate and pyruvate via the activity of lactate dehydrogenase (LDH). Testosterone targets many of the processes activated at the onset of functional overload. However, the effect of aging on this metabolic plasticity at the onset of functional overload and how anabolic steroid administration modulates this response is not well understood. The purpose of this study was to determine if aging would alter overload-induced LDH activity and expression at the onset of functional overload and whether anabolic steroid administration would modulate this response. Five-month and 25-month male Fischer 344xF1 BRN were given nandrolone decanoate (ND) or sham injections for 14days and then the plantaris was functionally overloaded (OV) for 3days by synergist ablation. Aging reduced muscle LDH-A & LDH-B activity 70% (p<0.05). Aging also reduced LDH-A mRNA abundance, however there was no age effect on LDH-B mRNA abundance. In 5-month muscle, both ND and OV decreased LDH-A and LDH-B activity. However, there was no synergistic or additive effect. In 5-month muscle, ND and OV decreased LDH-A mRNA expression with no change in LDH-B expression. In 25-month muscle, ND and OV increased LDH-A and LDH-B activity. LDH-A mRNA expression was not altered by ND or OV in aged muscle. However, there was a main effect of OV to decrease LDH-B mRNA expression. There was also an age-induced LDH isoform shift. ND and OV treatment increased the "fast" LDH isoforms in aged muscle, whereas ND and OV increased the "slow" isoforms in young muscle. Our study provides evidence that aging alters aspects of skeletal muscle metabolic plasticity normally induced by overload and anabolic steroid

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

Steroid hormone runoff from agricultural test plots applied with municipal biosolids

USGS Publications Warehouse

Yang, Yun-Ya; Gray, James L.; Furlong, Edward T.; Davis, Jessica G.; ReVollo, Rhiannon C.; Borch, Thomas

2012-01-01

The potential presence of steroid hormones in runoff from sites where biosolids have been used as agricultural fertilizers is an environmental concern. A study was conducted to assess the potential for runoff of seventeen different hormones and two sterols, including androgens, estrogens, and progestogens from agricultural test plots. The field containing the test plots had been applied with biosolids for the first time immediately prior to this study. Target compounds were isolated by solid-phase extraction (water samples) and pressurized solvent extraction (solid samples), derivatized, and analyzed by gas chromatography–tandem mass spectrometry. Runoff samples collected prior to biosolids application had low concentrations of two hormones (estrone -1 and androstenedione -1) and cholesterol (22.5 ± 3.8 μg L-1). In contrast, significantly higher concentrations of multiple estrogens (-1), androgens (-1), and progesterone (-1) were observed in runoff samples taken 1, 8, and 35 days after biosolids application. A significant positive correlation was observed between antecedent rainfall amount and hormone mass loads (runoff). Hormones in runoff were primarily present in the dissolved phase (<0.7-μm GF filter), and, to a lesser extent bound to the suspended-particle phase. Overall, these results indicate that rainfall can mobilize hormones from biosolids-amended agricultural fields, directly to surface waters or redistributed to terrestrial sites away from the point of application via runoff. Although concentrations decrease over time, 35 days is insufficient for complete degradation of hormones in soil at this site.

Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis.

PubMed

Polyzos, Stergios A; Makras, Polyzois; Efstathiadou, Zoe; Anastasilakis, Athanasios D

2015-02-01

Intermittent parathyroid hormone (PTH) administration, acting through multiple signaling pathways, exerts an osteoanabolic effect on the skeleton that surpasses the effect of other antiosteoporotic agents. However, its efficacy is limited by the coupling effect and relatively common adverse events. Thus, the development of more sophisticated PTH receptor analogs seems imperative. In this review, the authors summarize the role of PTH signaling pathway in bone remodeling. The authors also summarize investigational analogs targeting this pathway, which may be potential treatments for osteoporosis. β-arrestins are multifunctional cytoplasmic molecules that are decisive for regulating intracellular PTH signaling. Recently, in preclinical studies, arrestin analogs have achieved the anabolic bone effect of PTH without an accompanying increase in bone resorption. However, it is not yet known whether these analogs have adverse effects and there are no clinical data for their efficacy to date. On the other hand, several molecules derived either from PTH and PTH-related protein (PTHrP) molecules have been developed. Alternative routes of PTH 1 - 34 delivery (oral, transdermal), the PTH analog ostabolin and the N-terminal PTHrP analogs PTHrP 1 - 36 and abaloparatide, have recently been or are currently being tested in clinical trials and are more likely to become available for use in the near future.

Ipamorelin, the first selective growth hormone secretagogue.

PubMed

Raun, K; Hansen, B S; Johansen, N L; Thøgersen, H; Madsen, K; Ankersen, M; Andersen, P H

1998-11-01

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The

Effects of 𝛽-Hydroxy-𝛽-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training

PubMed Central

Asadi, Abbas; Arazi, Hamid

2017-01-01

Background: β-Hydroxy-β-methylbutyrate-free acid (HMB-FA) has been ingested prior to exercise to reduce muscle damage, however the effects of HMB-FA supplementation on hormonal, strength and power adaptation are unclear. Methods: Sixteen healthy men were matched and randomized into two groups and performed six-week resistance training while supplementing with either HMB-FA or placebo (3 g per day). The subjects were evaluated for 1 repetition maximum (1RM) bench press and leg press and vertical jump (VJ) prior to and after training intervention. In addition, blood samples were obtained before and after resistance training to evaluate resting growth hormone (GH), insulin like growth factor 1 (IGF-1), testosterone (TEST), cortisol (CORT), and adrenocorticotropic hormone (ACTH) responses. The HMB-FA supplementation group showed greater gains compared with the placebo group in peak power (effect size ES = 0.26 vs. 0.01) and 1RM leg press (ES = 1.52 vs. 0.96). In addition, the HMB-FA supplementation group indicated greater decrements in ACTH and CORT responses to training in comparison to the placebo group (p < 0.05). Likewise, in GH (ES = 1.41 vs. 0.12) and IGF-1 (ES = 0.83 vs. 0.41), the HMB-FA indicated greater training effects when compared with the placebo group. Conclusions: These findings provide further support for the potential anabolic benefits associated with HMB-FA supplementation. PMID:29207472

Adolescent Self-Perceptions and Attitudes toward School as Determinants of Anabolic-Androgenic Steroid Risk Estimates and Normative Judgments

ERIC Educational Resources Information Center

Denham, Bryan E.

2011-01-01

Grounded in symbolic interactionism and drawing on data gathered in the 2007 Monitoring the Future Study (n = 2,201), this research examines how self-esteem and perceived intelligence, as well as attitudes and behaviors related to school environments, associate with perceptions of anabolic-androgenic steroids. With perceived risk and…

Androgenic-anabolic steroids inhibited post-exercise hypotension: a case control study.

PubMed

Junior, Jefferson F C R; Silva, Alexandre S; Cardoso, Glêbia A; Silvino, Valmir O; Martins, Maria C C; Santos, Marcos A P

There is evidence of hypertensive effects caused by anabolic androgenic steroids (AAS). A single exercise session promotes the acute reduction of blood pressure, but the effects of AAS on this phenomenon are unknown. To investigate the post-exercise blood pressure response in androgenic-anabolic steroid users. Thirteen AAS users (23.9±4.3 years old) and sixteen controls (22.1±4.5 years old) performed a session of aerobic exercise. Heart rate and blood pressure were assessed before exercise and during a 60min post-exercise resting period. Repeated ANOVA measures were used to determine differences between the groups. While the control group had a significant reduction in post-exercise systolic blood pressure of up to 13.9±11.6mmHg at 40min, this phenomenon was limited among AAS users who reached a maximum of 6.2±11.5mmHg at 60min. The between groups comparison revealed significant higher post-exercise hypotension (PEH) for the control group at 30min (-12.9±14.1mmHg versus -2.9±7.6mmHg), 40min (-13.9±11.6mmHg versus -2.5±8.3mmHg), 50min (-13.9±13.9mmHg versus -5.0±7.9mmHg) and 60min (-12.5±12.8mmHg versus -6.2±11.5mmHg). There was no significant diastolic PEH in any of the groups. This study demonstrated impaired systolic post-exercise hypotension as a new adverse effect of AAS usage. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Rapid, portable detection of endocrine disrupting chemicals through ligand-nuclear hormone receptor interactions.

PubMed

Hunt, J Porter; Schinn, Song-Min; Jones, Matthew D; Bundy, Bradley C

2017-12-04

Endocrine disrupting chemicals (EDC) are structurally diverse compounds that can interact with nuclear hormone receptors, posing significant risk to human and ecological health. Unfortunately, many conventional biosensors have been too structure-specific, labor-intensive or laboratory-oriented to detect broad ranges of EDC effectively. Recently, several technological advances are providing more rapid, portable, and affordable detection of endocrine-disrupting activity through ligand-nuclear hormone receptor interactions. Here, we overview these recent advances applied to EDC biosensors - including cell lyophilization, cell immobilization, cell-free systems, smartphone-based signal detection, and improved competitive binding assays.

(−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

PubMed Central

2015-01-01

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

PubMed

Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

1992-02-01

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

PubMed Central

Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

1992-01-01

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women.

PubMed

Smith, Gordon I; Atherton, Philip; Reeds, Dominic N; Mohammed, B Selma; Rankin, Debbie; Rennie, Michael J; Mittendorfer, Bettina

2011-09-01

Increased dietary LCn-3PUFA (long-chain n-3 polyunsaturated fatty acid) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn-3PUFAs elicit similar anabolic effects in healthy individuals. To answer this question, we evaluated the effect of 8 weeks of LCn-3PUFA supplementation (4 g of Lovaza®/day) in nine 25-45-year-old healthy subjects on the rate of muscle protein synthesis (by using stable isotope-labelled tracer techniques) and the activation (phosphorylation) of elements of the mTOR (mammalian target of rapamycin)/p70S6K (p70 S6 kinase) signalling pathway during basal post-absorptive conditions and during a hyperinsulinaemic-hyperaminoacidaemic clamp. We also measured the concentrations of protein, RNA and DNA in muscle to obtain indices of the protein synthetic capacity, translational efficiency and cell size. Neither the basal muscle protein fractional synthesis rate nor basal signalling element phosphorylation changed in response to LCn-3PUFA supplementation, but the anabolic response to insulin and amino acid infusion was greater after LCn-3PUFA [i.e. the muscle protein fractional synthesis rate during insulin and amino acid infusion increased from 0.062±0.004 to 0.083±0.007%/h and the phospho-mTOR (Ser2448) and phospho-p70S6K (Thr389) levels increased by ∼50%; all P<0.05]. In addition, the muscle protein concentration and the protein/DNA ratio (i.e. muscle cell size) were both greater (P<0.05) after LCn-3PUFA supplementation. We conclude that LCn-3PUFAs have anabolic properties in healthy young and middle-aged adults.

Cerebral infarction in a young man using high-dose anabolic steroids.

PubMed

Shimada, Yoshiaki; Yoritaka, Asako; Tanaka, Yasutaka; Miyamoto, Nobukazu; Ueno, Yuji; Hattori, Nobutaka; Takao, Urabe

2012-11-01

Anabolic androgenic steroid (AAS) abuse has increased among athletes in recent years. However, AAS abuse can increase hypercoagulopathy and cause cerebrovascular disease. We report a case of a 27-year-old man who had right hemiparalysis, hemianopia, dysarthria, and double vision in the middle of muscle training. He suspected acute disseminated encephalomyelitis at first, because of a preceding respiratory infection. However, extensive work-up was performed, including brain magnetic resonance imaging, transcranial Doppler and transesophageal echocardiography, confirming the final diagnosis of cardioembolic stroke. Physicians should be aware that cerebrovascular disease may be a side effect of AAS, even in younger populations. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Intravascular ultrasound and angiographic demonstration of left main stem thrombus-high-risk presentation in a young adult with anabolic steroid abuse.

PubMed

Garg, Pankaj; Davis, Gershan; Wilson, John Ian; Sivananthan, Mohan

2010-01-01

We present a case of acute myocardial infarction in a young adult with a history of anabolic steroid abuse. On diagnostic coronary angiography and intravascular ultrasound, he was found to have a distal left main stem thrombus extending into the proximal left anterior descending artery and a large intermediate vessel. As he was hemodynamically stable and pain-free, he was managed conservatively with triple antiplatelet therapy (aspirin, clopidogrel, and abciximab). This was also to avoid the risk of 'wiring the vessel,' especially if there was underlying dissection. Repeat angiography a few weeks later showed complete thrombus resolution. This is the first reported case of extensive left main stem thrombus in a young patient with anabolic steroid abuse. Management of such cases is not straightforward and our case highlights one approach to both diagnosis and treatment.

Mechanisms of anabolic androgenic steroid inhibition of mammalian ɛ-subunit-containing GABAA receptors

PubMed Central

Jones, Brian L; Whiting, Paul J; Henderson, Leslie P

2006-01-01

GABAergic transmission regulates the activity of gonadotrophin-releasing hormone (GnRH) neurons in the preoptic area/hypothalamus that control the onset of puberty and the expression of reproductive behaviours. One of the hallmarks of illicit use of anabolic androgenic steroids (AAS) is disruption of behaviours under neuroendocrine control. GnRH neurons are among a limited population of cells that express high levels of the ɛ-subunit of the GABAA receptor. To better understand the actions of AAS on neuroendocrine mechanisms, we have characterized modulation of GABAA receptor-mediated currents in mouse native GnRH neurons and in heterologous cells expressing recombinant α2β3ɛ-receptors. GnRH neurons exhibited robust currents in response to millimolar concentrations of GABA and a picrotoxin (PTX)-sensitive, bicuculline-insensitive current that probably arises from spontaneous openings of GABAA receptors. The AAS 17α-methyltestosterone (17α-MeT) inhibited spontaneous and GABA-evoked currents in GnRH neurons. For recombinant α2β3ɛ-receptors, 17α-MeT inhibited phasic and tonic GABA-elicited responses, accelerated desensitization and slowed paired pulse response recovery. Single channel analysis indicated that GABA-evoked events could be described by three open dwell components and that 17α-MeT enhanced residence in the intermediate dwell state. This AAS also inhibited a PTX-sensitive, spontaneous current (open probability, ∼0.15–0.2) in a concentration-dependent fashion (IC50 ≈ 9 μm). Kinetic modelling indicated that the inhibition induced by 17α-MeT occurs by an allosteric block in which the AAS interacts preferentially with a closed state and promotes accumulation in that state. Finally, studies with a G302S mutant ɛ-subunit suggest that this residue within the transmembrane domain TM2 plays a role in mediating AAS binding and modulation. In sum, our results indicate that inclusion of the ɛ-subunit significantly alters the profile of AAS

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.

Inherited antithrombin deficiency and anabolic steroids: a risky combination.

PubMed

Choe, Hannah; Elfil, Mohamed; DeSancho, Maria T

2016-09-01

A 20-year-old male with asymptomatic inherited type 1 antithrombin deficiency and a family history of thrombosis started injecting himself with testosterone 250 mg intramuscularly twice weekly for 5 weeks. He presented to the hospital with progressive dyspnea on exertion, chest pain and hemoptysis. Workup revealed bilateral submassive pulmonary embolism and proximal right lower extremity deep vein thrombosis. He was treated with intravenous (IV) unfractionated heparin and underwent catheter-directed thrombolysis with alteplase to the main pulmonary arteries. Postprocedure, he remained on IV alteplase infusion for 24 h and unfractionated heparin in the intensive care unit. Concomitantly he received plasma-derived antithrombin concentrate. He was transitioned to subcutaneous enoxaparin twice daily and discharged from the hospital on oral rivaroxaban 15 mg twice a day. This case highlights the heightened thrombogenic effect of anabolic steroids in the setting of underlying thrombophilia especially in younger subjects.

N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

USDA-ARS?s Scientific Manuscript database

Context: Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (L...

Conserved steroid hormone homology converges on NFκB to modulate inflammation in asthma

PubMed Central

Payne, Asha S.; Freishtat, Robert J.

2012-01-01

Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity [1], yet has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing. Despite the complex pathogenesis of asthma, steroid hormones (e.g. glucocorticoids) are ubiquitous in the acute and chronic management of all types of asthma. Overall, steroid hormones are a class of widely-relevant, biologically-active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they employ rapid, non-genomic actions to affect cellular products. Steroid hormones are comprised of several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggest that each of these is part of dynamic system of hormone interaction, likely involving overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these three groups of steroid hormones (i.e. glucocorticoids, sex steroid hormones, and secosteroids), identifying NFκB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (e.g. glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be better understanding of the interplay of classical, non-classical, and non-genomic steroid hormone function. However, clues from the conserved homology steroid hormone structure and function and signaling pathways, offer insight into a possible model of steroid

Analysis of anabolic steroids in urine by gas chromatography-microchip atmospheric pressure photoionization-mass spectrometry with chlorobenzene as dopant.

PubMed

Hintikka, Laura; Haapala, Markus; Kuuranne, Tiia; Leinonen, Antti; Kostiainen, Risto

2013-10-18

A gas chromatography-microchip atmospheric pressure photoionization-tandem mass spectrometry (GC-μAPPI-MS/MS) method was developed for the analysis of anabolic androgenic steroids in urine as their trimethylsilyl derivatives. The method utilizes a heated nebulizer microchip in atmospheric pressure photoionization mode (μAPPI) with chlorobenzene as dopant, which provides high ionization efficiency by producing abundant radical cations with minimal fragmentation. The performance of GC-μAPPI-MS/MS was evaluated with respect to repeatability, linearity, linear range, and limit of detection (LOD). The results confirmed the potential of the method for doping control analysis of anabolic steroids. Repeatability (RSD<10%), linearity (R(2)≥0.996) and sensitivity (LODs 0.05-0.1ng/mL) were acceptable. Quantitative performance of the method was tested and compared with that of conventional GC-electron ionization-MS, and the results were in good agreement. Copyright © 2013 Elsevier B.V. All rights reserved.

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, ...

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).

Gas chromatography/chemical ionization triple quadrupole mass spectrometry analysis of anabolic steroids: ionization and collision-induced dissociation behavior.

PubMed

Polet, Michael; Van Gansbeke, Wim; Van Eenoo, Peter; Deventer, Koen

2016-02-28

The detection of new anabolic steroid metabolites and new designer steroids is a challenging task in doping analysis. Switching from electron ionization gas chromatography triple quadrupole mass spectrometry (GC/EI-MS/MS) to chemical ionization (CI) has proven to be an efficient way to increase the sensitivity of GC/MS/MS analyses and facilitate the detection of anabolic steroids. CI also extends the possibilities of GC/MS/MS analyses as the molecular ion is retained in its protonated form due to the softer ionization. In EI it can be difficult to find previously unknown but expected metabolites due to the low abundance or absence of the molecular ion and the extensive (and to a large extent unpredictable) fragmentation. The main aim of this work was to study the CI and collision-induced dissociation (CID) behavior of a large number of anabolic androgenic steroids (AAS) as their trimethylsilyl derivatives in order to determine correlations between structures and CID fragmentation. Clarification of these correlations is needed for the elucidation of structures of unknown steroids and new metabolites. The ionization and CID behavior of 65 AAS have been studied using GC/CI-MS/MS with ammonia as the reagent gas. Glucuronidated AAS reference standards were first hydrolyzed to obtain their free forms. Afterwards, all the standards were derivatized to their trimethylsilyl forms. Full scan and product ion scan analyses were used to examine the ionization and CID behavior. Full scan and product ion scan analyses revealed clear correlations between AAS structure and the obtained mass spectra. These correlations were confirmed by analysis of multiple hydroxylated, methylated, chlorinated and deuterated analogs. AAS have been divided into three groups according to their ionization behavior and into seven groups according to their CID behavior. Correlations between fragmentation and structure were revealed and fragmentation pathways were postulated. Copyright © 2016 John Wiley

Anti-tumor effects of peptide analogs targeting neuropeptide hormone receptors on mouse pheochromocytoma cells.

PubMed

Ziegler, C G; Ullrich, M; Schally, A V; Bergmann, R; Pietzsch, J; Gebauer, L; Gondek, K; Qin, N; Pacak, K; Ehrhart-Bornstein, M; Eisenhofer, G; Bornstein, S R

2013-05-22

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle-Aged Men

PubMed Central

Emeville, Elise; Giton, Frank; Giusti, Arnaud; Oliva, Alejandro; Fiet, Jean; Thomé, Jean-Pierre; Blanchet, Pascal; Multigner, Luc

2013-01-01

Background Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern

Sudden or unnatural deaths involving anabolic-androgenic steroids.

PubMed

Darke, Shane; Torok, Michelle; Duflou, Johan

2014-07-01

Anabolic-androgenic steroids (AASs) are frequently misused. To determine causes of death, characteristics, toxicology, and pathology of AAS positive cases, all cases (n = 24) presenting to the New South Wales Department of Forensic Medicine (1995-2012) were retrieved. All were male, and the mean age was 31.7 years. Deaths were mainly due to accidental drug toxicity (62.5%), then suicide (16.7%) and homicide (12.5%). Abnormal testosterone/epitestosterone ratios were reported in 62.5%, followed by metabolites of nandrolone (58.3%), stanozolol (33.3%), and methandienone (20.8%). In 23 of 24 cases, substances other than steroids were detected, most commonly psychostimulants (66.7%). In nearly half, testicular atrophy was noted, as was testicular fibrosis and arrested spermatogenesis. Left ventricular hypertrophy was noted in 30.4%, and moderate to severe narrowing of the coronary arteries in 26.1%. To summarize, the typical case was a male polydrug user aged in their thirties, with death due to drug toxicity. Extensive cardiovascular disease was particularly notable. © 2014 American Academy of Forensic Sciences.

Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I

NASA Technical Reports Server (NTRS)

Kostenuik, P. J.; Harris, J.; Halloran, B. P.; Turner, R. T.; Morey-Holton, E. R.; Bikle, D. D.

1999-01-01

Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.

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...

Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men.

PubMed

Morton, Robert W; Oikawa, Sara Y; Wavell, Christopher G; Mazara, Nicole; McGlory, Chris; Quadrilatero, Joe; Baechler, Brittany L; Baker, Steven K; Phillips, Stuart M

2016-07-01

We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and strength improvements in RT-naïve subjects. Here we aimed to determine whether the same was true in men with previous RT experience using a whole-body RT program and whether postexercise systemic hormone concentrations were related to changes in hypertrophy and strength. Forty-nine resistance-trained men (23 ± 1 yr, mean ± SE) performed 12 wk of whole-body RT. Subjects were randomly allocated into a higher-repetition (HR) group who lifted loads of ∼30-50% of their maximal strength (1RM) for 20-25 repetitions/set (n = 24) or a lower-repetition (LR) group (∼75-90% 1RM, 8-12 repetitions/set, n = 25), with all sets being performed to volitional failure. Skeletal muscle biopsies, strength testing, dual-energy X-ray absorptiometry scans, and acute changes in systemic hormone concentrations were examined pretraining and posttraining. In response to RT, 1RM strength increased for all exercises in both groups (P < 0.01), with only the change in bench press being significantly different between groups (HR, 9 ± 1, vs. LR, 14 ± 1 kg, P = 0.012). Fat- and bone-free (lean) body mass and type I and type II muscle fiber cross-sectional area increased following training (P < 0.01) with no significant differences between groups. No significant correlations between the acute postexercise rise in any purported anabolic hormone and the change in strength or hypertrophy were found. In congruence with our previous work, acute postexercise systemic hormonal rises are not related to or in any way indicative of RT-mediated gains in muscle mass or strength. Our data show that in resistance-trained individuals, load, when exercises are performed to volitional failure, does not dictate hypertrophy or, for the most part, strength gains. Copyright © 2016 the American Physiological Society.

The current state of knowledge on the neuroactive compounds that affect the development, mating and reproduction of spiders (Araneae) compared to insects.

PubMed

Sawadro, Marta; Bednarek, Agata; Babczyńska, Agnieszka

2017-06-01

The neuroendocrine system of insects, including the presence of the main neuroactive compounds, and their role in ontogenesis are probably best understood of all the arthropods. Development, metamorphosis, the maturation of the gonads, vitellogenesis and egg production are regulated by hormones (juvenile hormones, ecdysteroids) and neuropeptides. However, knowledge about their presence and functions in spiders is fragmentary. In this paper, we present a summary of the current data about the juvenile hormones, ecdysteroids and neuropeptides in selected groups of arthropods, with particular emphasis on spiders. This is the first article that takes into account the occurrence, action and role of hormones and neuropeptides in spiders. In addition, the suggestions for possible ways to study these compounds in Araneomorphae spiders are unique and cannot be found in the arachnological literature.

Embryonic treatment with xenobiotics disrupts steroid hormone profiles in hatchling red-eared slider turtles (Trachemys scripta elegans).

PubMed Central

Willingham, E; Rhen, T; Sakata, J T; Crews, D

2000-01-01

Many compounds in the environment capable of acting as endocrine disruptors have been assayed for their developmental effects on morphogenesis; however, few studies have addressed how such xenobiotics affect physiology. In the current study we examine the effects of three endocrine-disrupting compounds, chlordane, trans-nonachlor, and the polychlorinated biphenyl (PCB) mixture Aroclor 1242, on the steroid hormone concentrations of red-eared slider turtle (Trachemys scripta elegans) hatchlings treated in ovo. Basal steroid concentrations and steroid concentrations in response to follicle-stimulating hormone were examined in both male and female turtles treated with each of the three compounds. Treated male turtles exposed to Aroclor 1242 or chlordane exhibited significantly lower testosterone concentrations than controls, whereas chlordane-treated females had significantly lower progesterone, testosterone, and 5[alpha]-dihydrotestosterone concentrations relative to controls. The effects of these endocrine disruptors extend beyond embryonic development, altering sex-steroid physiology in exposed animals. Images Figure 1 Figure 2 PMID:10753091

Screening hybridomas for anabolic androgenic steroids by steroid analog antigen microarray.

PubMed

Du, Hongwu; Chen, Guangyu; Bian, Yongzhong; Xing, Cenzan; Ding, Xue; Zhu, Mengliang; Xun, Yiping; Chen, Peng; Zhou, Yabin; Li, Shaoxu

2015-01-01

Currently, dozens of anabolic androgenic steroids (AAS) are forbidden in the World Anti-Doping Agency Prohibited List, however, despite extensive investigation, there are still lots of AAS without corresponding monoclonal antibodies. A steroid analog antigen microarray made up of ten AAS was fabricated to screen the hybridoma and it was found an original unsuccessful clone turned out to be a candidate anti-boldenone antibody, without any cross-reactions with endogenous AAS or 44 different AAS standard reference materials tested. Our findings suggested that steroid analog antigen microarray could be a promising tool to screen and characterize new applications of antibodies for structure analogs, and this also exhibits the potential to fast identify effective epitopes of hybridomas in a single assay.

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

NASA Technical Reports Server (NTRS)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.

PubMed

Willoughby, Darryn S; Leutholtz, Brian

2013-10-01

It was hypothesized that D-aspartic acid (D-ASP) supplementation would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, body composition, muscle strength, and serum hormone levels associated with the hypothalamo-pituitary-gonadal axis were studied after 28 days of resistance training and D-ASP supplementation. Resistance-trained men resistance trained 4 times/wk for 28 days while orally ingesting either 3 g of placebo or 3 g of D-ASP. Data were analyzed with 2 × 2 analysis of variance (P < .05). Before and after resistance training and supplementation, body composition and muscle strength, serum gonadal hormones, and serum D-ASP and d-aspartate oxidase (DDO) were determined. Body composition and muscle strength were significantly increased in both groups in response to resistance training (P < .05) but not different from one another (P > .05). Total and free testosterone, luteinizing hormone, gonadotropin-releasing hormone, and estradiol were unchanged with resistance training and D-ASP supplementation (P > .05). For serum D-ASP and DDO, D-ASP resulted in a slight increase compared with baseline levels (P > .05). For the D-ASP group, the levels of serum DDO were significantly increased compared with placebo (P < .05). The gonadal hormones were unaffected by 28 days of D-ASP supplementation and not associated with the observed increases in muscle strength and mass. Therefore, at the dose provided, D-ASP supplementation is ineffective in up-regulating the activity of the hypothalamo-pituitary-gonadal axis and has no anabolic or ergogenic effects in skeletal muscle. © 2013 Elsevier Inc. All rights reserved.

Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners.

PubMed

Yahiro, J; Glass, A R; Fears, W B; Ferguson, E W; Vigersky, R A

1987-03-01

Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 micrograms intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 micrograms intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were similar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We concluded that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in "stress-induced" or "psychogenic" amenorrhea.

Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism

PubMed Central

Cai, Bin; Li, Wenjun; Mao, XiaoOu; Winters, Ali; Ryou, Myoung-Gwi; Liu, Ran; Greenberg, David A.; Wang, Ning; Jin, Kunlin; Yang, Shao-Hua

2017-01-01

Neuroglobin (Ngb) is a recently discovered globin with preferential localization to neurons. Growing evidence indicates that Ngb has distinct physiological functions separate from the oxygen storage and transport roles of other globins, such as hemoglobin and myoglobin. We found increased ATP production and decreased glycolysis in Ngb-overexpressing immortalized murine hippocampal cell line (HT-22), in parallel with inhibition of AMPK signaling and activation of acetyl-CoA carboxylase (ACC). In addition, lipid and glycogen content was increased in Ngb-overexpressing HT-22 cells. AMPK signaling was also inhibited in brain and heart from Ngb-overexpressing transgenic mice. Although Ngb overexpression did not change glycogen content in whole brain, glycogen synthase was activated in cortical neurons of Ngb overexpressing mouse brain and Ngb overexpression primary neurons. Moreover, lipid and glycogen content was increased in hearts derived from Ngb-overexpressing mice. These findings suggest that Ngb functions as a metabolic regulator and enhances cellular anabolism through the inhibition of AMPK signaling. PMID:25616953

Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism.

PubMed

Cai, Bin; Li, Wenjun; Mao, XiaoOu; Winters, Ali; Ryou, Myoung-Gwi; Liu, Ran; Greenberg, David A; Wang, Ning; Jin, Kunlin; Yang, Shao-Hua

2016-03-01

Neuroglobin (Ngb) is a recently discovered globin with preferential localization to neurons. Growing evidence indicates that Ngb has distinct physiological functions separate from the oxygen storage and transport roles of other globins, such as hemoglobin and myoglobin. We found increased ATP production and decreased glycolysis in Ngb-overexpressing immortalized murine hippocampal cell line (HT-22), in parallel with inhibition of AMP-activated protein kinase (AMPK) signaling and activation of acetyl-CoA carboxylase (ACC). In addition, lipid and glycogen content was increased in Ngb-overexpressing HT-22 cells. AMPK signaling was also inhibited in the brain and heart from Ngb-overexpressing transgenic mice. Although Ngb overexpression did not change glycogen content in whole brain, glycogen synthase was activated in cortical neurons of Ngb-overexpressing mouse brain and Ngb overexpression primary neurons. Moreover, lipid and glycogen content was increased in hearts derived from Ngb-overexpressing mice. These findings suggest that Ngb functions as a metabolic regulator and enhances cellular anabolism through the inhibition of AMPK signaling.

Hormone therapy in acne.

PubMed

Lakshmi, Chembolli

2013-01-01

Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

Steroid plant hormones: effects outside plant kingdom.

PubMed

Zhabinskii, Vladimir N; Khripach, Natalia B; Khripach, Vladimir A

2015-05-01

Brassinosteroids (BS) are the first group of steroid-hormonal compounds isolated from and acting in plants. Among numerous physiological effects of BS growth stimulation and adaptogenic activities are especially remarkable. In this review, we provide evidence that BS possess similar types of activity also beyond plant kingdom at concentrations comparable with those for plants. This finding allows looking at steroids from a new point of view: how common are the mechanisms of steroid bioregulation in different types of organisms from protozoa to higher animals. Copyright © 2014 Elsevier Inc. All rights reserved.

Statistical analysis of fragmentation patterns of electron ionization mass spectra of enolized-trimethylsilylated anabolic androgenic steroids

NASA Astrophysics Data System (ADS)

Fragkaki, A. G.; Angelis, Y. S.; Tsantili-Kakoulidou, A.; Koupparis, M.; Georgakopoulos, C.

2009-08-01

Anabolic androgenic steroids (AAS) are included in the List of prohibited substances of the World Anti-Doping Agency (WADA) as substances abused to enhance athletic performance. Gas chromatography coupled to mass spectrometry (GC-MS) plays an important role in doping control analyses identifying AAS as their enolized-trimethylsilyl (TMS)-derivatives using the electron ionization (EI) mode. This paper explores the suitability of complementary GC-MS mass spectra and statistical analysis (principal component analysis, PCA and partial least squares-discriminant analysis, PLS-DA) to differentiate AAS as a function of their structural and conformational features expressed by their fragment ions. The results obtained showed that the application of PCA yielded a classification among the AAS molecules which became more apparent after applying PLS-DA to the dataset. The application of PLS-DA yielded a clear separation among the AAS molecules which were, thus, classified as: 1-ene-3-keto, 3-hydroxyl with saturated A-ring, 1-ene-3-hydroxyl, 4-ene-3-keto, 1,4-diene-3-keto and 3-keto with saturated A-ring anabolic steroids. The study of this paper also presents structurally diagnostic fragment ions and dissociation routes providing evidence for the presence of unknown AAS or chemically modified molecules known as designer steroids.

Strigolactones are a new-defined class of plant hormones which inhibit shoot branching and mediate the interaction of plant-AM fungi and plant-parasitic weeds.

PubMed

Chen, Caiyan; Zou, Junhuang; Zhang, Shuying; Zaitlin, David; Zhu, Lihuang

2009-08-01

Because plants are sessile organisms, the ability to adapt to a wide range of environmental conditions is critical for their survival. As a consequence, plants use hormones to regulate growth, mitigate biotic and abiotic stresses, and to communicate with other organisms. Many plant hormones function pleiotropically in vivo, and often work in tandem with other hormones that are chemically distinct. A newly-defined class of plant hormones, the strigolactones, cooperate with auxins and cytokinins to control shoot branching and the outgrowth of lateral buds. Strigolactones were originally identified as compounds that stimulated the germination of parasitic plant seeds, and were also demonstrated to induce hyphal branching in arbuscular mycorrhizal (AM) fungi. AM fungi form symbioses with higher plant roots and mainly facilitate the absorption of phosphate from the soil. Conforming to the classical definition of a plant hormone, strigolactones are produced in the roots and translocated to the shoots where they inhibit shoot outgrowth and branching. The biosynthesis of this class of compounds is regulated by soil nutrient availability, i.e. the plant will increase its production of strigolactones when the soil phosphate concentration is limited, and decrease production when phosphates are in ample supply. Strigolactones that affect plant shoot branching, AM fungal hyphal branching, and seed germination in parasitic plants facilitate chemical synthesis of similar compounds to control these and other biological processes by exogenous application.

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

Anabolic Steroid Misuse among Minors. Report to the Governor and the General Assembly of Virginia. House Document No. 58.

ERIC Educational Resources Information Center

Virginia State Health Professions Dept., Richmond.

This document comprises the final report of the Virginia Department of Health Professions' Task Force on anabolic steroid misuse among minors. As such, it summarizes the activities of the department and of the boards within the department, the Offices of the Secretary of Health and Education, and other organizations including the Virginia High…

Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report

PubMed Central

2013-01-01

Introduction Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Case presentation Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. Conclusions The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome. PMID:24377430

Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report.

PubMed

Adachi, Masanori; Tajima, Toshihiro; Muroya, Koji; Asakura, Yumi

2013-12-30

Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome.

Predictors of future anabolic androgenic steroid use.

PubMed

Wichstrøm, Lars

2006-09-01

To prospectively study the stability of anabolic androgenic steroid (AAS) use and predictors of AAS use, and to investigate whether AAS use alters the risk of later emotional and behavioral problems. Survey of a national sample of Norwegian high school students (age 15-19) in 1994 followed up in 1999 (N = 2924). Measures of frequent alcohol intoxication (50+ times per 12 months), cannabis use (12 months), hard drug use (12 months), being offered cannabis, eating problems, conduct problems, sexual debut before age 15, BMI, involvement in power sports, perceived physical appearance, and satisfaction with body parts were obtained. Life-time prevalence of AAS use were 1.9 and 0.8% in the follow-up period. Multivariate logistic regression revealed that future AAS use was predicted by young age, male gender, previous AAS use, involvement in power sports, and frequent alcohol intoxication. AAS use did not predict future emotional or behavioral problems other than reducing the risk of future frequent alcohol intoxication. Frequent alcohol intoxication and involvement in power sports appear to predict future AAS use. At the population level there was little stability in individual AAS use from adolescence to early adulthood. No detrimental effects of AAS use could be detected in this study, but low statistical power limits this conclusion.

Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem.

PubMed

Melnik, Bodo; Jansen, Thomas; Grabbe, Stephan

2007-02-01

Abuse of anabolic-androgenic steroids (AAS) by members of fitness centers and others in Germany has reached alarming dimensions. The health care system provides the illegal AAS to 48.1 % of abusers. Physicians are involved in illegal prescription of AAS and monitoring of 32.1 % of AAS abusers. Besides health-threatening cardiovascular, hepatotoxic and psychiatric long-term side effects of AAS, acne occurs in about 50 % of AAS abusers and is an important clinical indicator of AAS abuse, especially in young men 18-26 years of age. Both acne conglobata and acne fulminans can be induced by AAS abuse. The dermatologist should recognize bodybuilding acne, address the AAS abuse, and warn the patient about other potential hazards.

The Sturm und Drang of anabolic steroid use: angst, anxiety, and aggression

PubMed Central

Oberlander, Joseph G.; Henderson, Leslie P.

2014-01-01

Anabolic androgenic steroids (AAS) are illicitly administered to enhance athletic performance and body image. Although conferring positive actions on performance, steroid abuse is associated with changes in anxiety and aggression. AAS users are often keenly invested in understanding the biological actions of these drugs. Thus, mechanistic information on AAS actions is important not only for the biomedical community, but also for steroid users. Here we review findings from animal studies on the impact of AAS exposure on neural systems that are crucial for the production of anxiety and aggression, and compare the effects of the different classes of AAS and their potential signaling mechanisms, as well as context-, age- and sex-dependent aspects of their actions. PMID:22516619

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions.

PubMed

Phillips, Bethan E; Atherton, Philip J; Varadhan, Krishna; Wilkinson, Daniel J; Limb, Marie; Selby, Anna L; Rennie, Michael J; Smith, Kenneth; Williams, John P

2014-01-15

Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 ± 2.1 yr) under postabsorptive and fed [iv Glamin (∼10 g AA), glucose ∼7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-(13)C2]leucine and [(2)H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12 ± 5%, P < 0.05), MBV (+25 ± 10%, P < 0.05), and MPS (+129 ± 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF (+126 ± 12%, P < 0.05) and MBV (+79 ± 30%, P < 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 ± 0.004 vs. 0.08 ± 0.01%/h, P < 0.05) nor improvements in NPB (-4.4 ± 2.4 vs. 16.4 ± 5.7 nmol Phe·100 ml leg(-1)·min(-1), P < 0.05) were affected by methacholine infusion (MPS 0.07 ± 0.01%/h; NPB 24.0 ± 7.7 nmol Phe·100 ml leg(-1)·min(-1)), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism.

Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

PubMed

Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

2017-12-01

Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.

PubMed

Lee, Su-Ui; Park, Sang-Joon; Kwak, Han Bok; Oh, Jaemin; Min, Yong Ki; Kim, Seong Hwan

2008-01-01

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone mass and improve bone architecture. In this study, we demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances differentiation and mineralization of osteoblasts in vitro. We found that ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs), inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid in the late stage of osteoblast differentiation. Importantly, ursolic acid was shown to have bone-forming activity in vivo in a mouse calvarial bone formation model. A high proportion of positive immunostaining of BMP-2 was found in the nuclear region of woven bone formed by ursolic acid. These results suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation.

Thyroid Hormone Receptor Antagonists: From Environmental Pollution to Novel Small Molecules.

PubMed

Mackenzie, Louise S

2018-01-01

Thyroid hormone receptors (TRs) are nuclear receptors which control transcription, and thereby have effects in all cells within the body. TRs are an important regulator in many basic physiological processes including development, growth, metabolism, and cardiac function. The hyperthyroid condition results from an over production of thyroid hormones resulting in a continual stimulation of thyroid receptors which is detrimental for the patient. Therapies for hyperthyroidism are available, but there is a need for new small molecules that act as TR antagonists to treat hyperthyroidism. Many compounds exhibit TR antagonism and are considered detrimental to health. Some drugs in the clinic (most importantly, amiodarone) and environmental pollution exhibit TR antagonist properties and thus have the potential to induce hypothyroidism in some people. This chapter provides an overview of novel small molecules that have been specifically designed or screened for their TR antagonist activity as novel treatments for hyperthyroidism. While novel compounds have been identified, to date none have been developed sufficiently to enter clinical trials. Furthermore, a discussion on other sources of TR antagonists is discussed in terms of side effects of current drugs in the clinic as well as environmental pollution. © 2018 Elsevier Inc. All rights reserved.

Improved strength of silk fibers in Bombyx mori trimolters induced by an anti-juvenile hormone compound.

PubMed

Guo, Kaiyu; Dong, Zhaoming; Zhang, Yan; Wang, Dandan; Tang, Muya; Zhang, Xiaolu; Xia, Qingyou; Zhao, Ping

2018-05-01

Bombyx mori silk fibers with thin diameters have advantages of lightness and crease-resistance. Many studies have used anti-juvenile hormones to induce trimolters in order to generate thin silk; however, there has been comparatively little analysis of the morphology, structure and mechanical properties of trimolter silk. This study induced two kinds of trimolters by appling topically anti-juvenile hormones and obtained thin diameter silk. Scanning electron microscope (SEM), FTIR analysis, tensile mechanical testing, chitin staining were used to reveal that the morphology, conformation and mechanical property of the trimolter silk. Cocoon of trimolters were highly densely packed by thinner fibers and thus had small apertures. We found that the conformation of trimolter silk fibroin changed and formed more β-sheet structures. In addition, analysis of mechanical parameters yielded a higher Young's modulus and strength in trimolter silk than in the control. By chitin staining of silk gland, we postulated that the mechanical properties of trimolters' silk was enhanced greatly during to the structural changes of silk gland. We induced trimolters by anti-juvenile hormones and the resulting cocoons were more closely packed and had smaller silk fiber diameters. We found that the conformation of trimolters silk fibroin had a higher content of β-sheet structures and better mechanical properties. Our study revealed the structures and mechanical properties of trimolter silk, and provided a valuable reference to improve silk quality by influencing molting in silkworms. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of compound-protein interactions through the analysis of gene ontology, KEGG enrichment for proteins and molecular fragments of compounds.

PubMed

Chen, Lei; Zhang, Yu-Hang; Zheng, Mingyue; Huang, Tao; Cai, Yu-Dong

2016-12-01

Compound-protein interactions play important roles in every cell via the recognition and regulation of specific functional proteins. The correct identification of compound-protein interactions can lead to a good comprehension of this complicated system and provide useful input for the investigation of various attributes of compounds and proteins. In this study, we attempted to understand this system by extracting properties from both proteins and compounds, in which proteins were represented by gene ontology and KEGG pathway enrichment scores and compounds were represented by molecular fragments. Advanced feature selection methods, including minimum redundancy maximum relevance, incremental feature selection, and the basic machine learning algorithm random forest, were used to analyze these properties and extract core factors for the determination of actual compound-protein interactions. Compound-protein interactions reported in The Binding Databases were used as positive samples. To improve the reliability of the results, the analytic procedure was executed five times using different negative samples. Simultaneously, five optimal prediction methods based on a random forest and yielding maximum MCCs of approximately 77.55 % were constructed and may be useful tools for the prediction of compound-protein interactions. This work provides new clues to understanding the system of compound-protein interactions by analyzing extracted core features. Our results indicate that compound-protein interactions are related to biological processes involving immune, developmental and hormone-associated pathways.

Hormonally active agents in the environment: a state-of-the-art review.

PubMed

Anwer, Faizan; Chaurasia, Savita; Khan, Abid Ali

2016-12-01

After the Second World War, infatuation with modern products has exponentially widened the spectrum of chemicals used. Some of them are capable of hijacking the endocrine system by blocking or imitating a hormone and are referred to as hormonally active chemicals or endocrine disruptors. These are chemicals that the body was not designed for evolutionarily and they are present in every matrix of the environment. We are living in a chemical world where the exposures are ubiquitous and take place in combinations that can interact with the endocrine system and some other metabolic activities in unexpected ways. The complexity of interaction of these compounds can be understood by the fact that they interfere with gene expression at extremely low levels, consequently harming an individual life form, its offspring or population. As the endocrine system plays a critical role in many biological or physiological functions, by interfering body's endocrine system, endocrine disrupting compounds (EDCs) have various adverse effects on human health, starting from birth defects to developmental disorders, deadly deseases like cancer and even immunological disorders. Most of these compounds have not been tested yet for safety and their effects cannot be assessed by the available techniques. The establishment of proper exposure measurement techniques and integrating correlation is yet to be achieved to completely understand the impacts at various levels of the endocrine axis.

HormoneBase, a population-level database of steroid hormone levels across vertebrates

PubMed Central

Vitousek, Maren N.; Johnson, Michele A.; Donald, Jeremy W.; Francis, Clinton D.; Fuxjager, Matthew J.; Goymann, Wolfgang; Hau, Michaela; Husak, Jerry F.; Kircher, Bonnie K.; Knapp, Rosemary; Martin, Lynn B.; Miller, Eliot T.; Schoenle, Laura A.; Uehling, Jennifer J.; Williams, Tony D.

2018-01-01

Hormones are central regulators of organismal function and flexibility that mediate a diversity of phenotypic traits from early development through senescence. Yet despite these important roles, basic questions about how and why hormone systems vary within and across species remain unanswered. Here we describe HormoneBase, a database of circulating steroid hormone levels and their variation across vertebrates. This database aims to provide all available data on the mean, variation, and range of plasma glucocorticoids (both baseline and stress-induced) and androgens in free-living and un-manipulated adult vertebrates. HormoneBase (www.HormoneBase.org) currently includes >6,580 entries from 476 species, reported in 648 publications from 1967 to 2015, and unpublished datasets. Entries are associated with data on the species and population, sex, year and month of study, geographic coordinates, life history stage, method and latency of hormone sampling, and analysis technique. This novel resource could be used for analyses of the function and evolution of hormone systems, and the relationships between hormonal variation and a variety of processes including phenotypic variation, fitness, and species distributions. PMID:29786693