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  1. Testosterone administration decreases generosity in the ultimatum game.

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    Paul J Zak

    Full Text Available How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72; 95% CI T: (.98, 2.30. This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT. Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially.

  2. Effects of testosterone administration on liver structure and function in aging rats.

    Science.gov (United States)

    Nucci, Ricardo Aparecido Baptista; Teodoro, Ana Caroline de Souza; Krause Neto, Walter; Silva, Wellington de Assis; de Souza, Romeu Rodrigues; Anaruma, Carlos Alberto; Gama, Eliane Florencio

    2017-06-01

    Aging males have a decrease in testosterone levels, by which the testosterone treatment may influence in a negatively fashion the liver. This study aimed to analyze the effects of aging with or without testosterone administration on the liver components of animals. Wistar rats were divided into three groups: 20 months' group (G20), 24 months' group (G24), group treated with testosterone for 16 weeks (GT). All groups were sacrificed at 24 months except for G20 that was sacrificed at 20 months. Aging and testosterone treatment alters the body weight (BW), liver weight (LW) and relative liver weight. Besides, testosterone increased the mitogen capacity of hepatocytes. Nonetheless, we reinforce the negative effects of testosterone on old animals' liver as chronic hepatic congestion and/or cholestasis. In addition, we observed that testosterone plays an important role on hepatic glycogen stores. Our study showed many implications for the knowledge about the effects of aging with or without testosterone administration on old animals' liver.

  3. Testosterone therapy decreases subcutaneous fat and adiponectin in aging men

    DEFF Research Database (Denmark)

    Frederiksen, L.; Højlund, K.; Hougaard, D. M.

    2012-01-01

    OBJECTIVE: Testosterone therapy increases lean body mass and decreases total fat mass in aging men with low normal testosterone levels. The major challenge is, however, to determine whether the metabolic consequences of testosterone therapy are overall positive. We have previously reported that 6......-month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels. DESIGN: A randomized......, double-blinded, placebo-controlled study on 6-month testosterone treatment (gel) in 38 men, aged 60–78 years, with bioavailable testosterone 94 cm. METHODS: Central fat mass (CFM) and lower extremity fat mass (LEFM) were measured by dual X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAT...

  4. Aluminum-induced testosterone decrease results in physiological ...

    African Journals Online (AJOL)

    user

    2011-01-10

    Jan 10, 2011 ... Recently, there has been much controversy on the role of testosterone on social and aggression behaviors. This work aimed to determine the effect of testosterone decrease, induced by aluminum exposure on the level of aggression. Male Swiss-Webster strain mice were classified into three groups.

  5. Cognitive effects of testosterone and finasteride administration in older hypogonadal men.

    Science.gov (United States)

    Borst, Stephen E; Yarrow, Joshua F; Fernandez, Carmen; Conover, Christine F; Ye, Fan; Meuleman, John R; Morrow, Matthew; Zou, Baiming; Shuster, Jonathan J

    2014-01-01

    Serum concentrations of neuroactive androgens decline in older men and, in some studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor), in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥ 60 years with a serum testosterone concentration of ≤ 300 ng/dL or bioavailable testosterone ≤ 70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week) versus vehicle, paired with finasteride (5 mg/day) versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies are warranted to determine if testosterone replacement may improve cognition in other domains.

  6. Evaluation of testosterone metabolites/dehydroepiandrosterone as the indicators of testosterone administration in horse doping

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.Y.; Kim, S.J. [Korea Racing Association, Kyonggi (Korea); Kyong, J.B. [Hanyang University, Seoul (Korea); Choi, M.H.; Chung, B.C. [Korea Institute of Science and Technology, Seoul (Korea)

    1999-06-01

    The metabolism of testosterone (17{beta}-hydroxy-androst-4-en-3-one) was confirmed in horse after a single intramuscular administration of testosterone cypionate (750 mg). Solvent extracts of urine obtained with enzymatic hydrolysis and methanolysis were analyzed by GC/MS after oxime t-butyldimethylsilyl (oxime-TBDMS) derivatization. the structures of four urinary metabolite after testosterone administration in horse were determined based on EI mass spectra and 5{alpha}-androstane-3{beta}, 17{alpha}-diol and 5a-androstane-3{beta}-ol--17one as major was confirmed with authentic standard. Also the concentrations of 5{alpha}--androstane-3{beta}, 17{alpha}-diol, 5{alpha}-androstane-3{beta}, 17{beta}-diol, dehydroepiandrosterone (DHEA), 5{alpha}-androstane-3{beta}-ol-17-one and testosterone were determined in the urine of normal subjects and the urine after administration. The recovery and detection limit in the most drugs were 86.3{approx}94.7% and 1{approx}3 ppb, respectively. Correlation coefficients for calibration were in the range of 0.984{approx}0.999. Excretion profile of testosterone presents the rapid and large increasement up to maximum values as days 5 after administration and the slow regression. The relative ratios of testosterone, its metabolites over DHEA were determined for indication of testosterone administration in horse doping. 13 refs., 5 figs., 1 tab.

  7. Aluminum-induced testosterone decrease results in physiological ...

    African Journals Online (AJOL)

    In contrast, at the high dose, acetylcholine recorded significantly high value. In conclusion, aluminum-induced testosterone decrease resulted in a significant decline in aggression, several blood parameters and levels of neurotransmitters. Keywords: Aluminum, Swiss-Webster mice, standard opponent test, social behavior, ...

  8. Androgens and oestrogens before and following oral testosterone administration in male patients with and without alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Dejgaard, A; Bennett, Patrick

    1987-01-01

    testosterone, serum concentrations of testosterone, dihydrotestosterone, androstenedione, and oestrone increased significantly (P less than 0.05) in both groups, cirrhotic patients reaching significantly (P less than 0.01) higher concentrations than controls. Further, in the cirrhotic group, the serum...... concentrations of oestrone sulphate, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol, and the urinary excretion of oestrogen increased significantly P less than 0.05). In conclusion, peroral testosterone administration decreases the serum oestradiol/testosterone ratio in patients...... than 0.05) lower concentrations of albumin and non-SHBG bound testosterone; no significant differences regarding concentrations of testosterone, dihydrotestosterone, non-protein bound testosterone, oestrone sulphate, and SHBG bound oestradiol. Following oral administration of 400 mg of micronized...

  9. Short-term parenteral and peroral testosterone administration in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick; Dietrichson, O

    1981-01-01

    Serum concentrations of testosterone were measured in 24 male patients with alcoholic cirrhosis during testosterone administration. The purpose was to compare serum concentrations of testosterone during peroral with those during parenteral testosterone administration in these patients. Patients who...... were injected intramuscularly with a combination of short- and long-acting testosterone (Triolandren, 348 mg testosterone) had median peak values of serum testosterone of about 40 ng/ml, which fell to basal levels after a fortnight. During testosterone propionate injections (84 mg testosterone) every...... other day, rather constant serum concentrations with median values of about 30 ng/ml were reached after 4 days. Peroral testosterone administration (800 mg micronized free testosterone) each day also resulted in fairly constant serum concentrations after 4 days, and the median values were about 50 ng...

  10. The effect of orchidectomy and administration of testosterone ...

    African Journals Online (AJOL)

    The effect of orchidectomy and administration of testosterone propionate or nandrolone phenylpropionate to orchidectomised rats on their growth and carcass composition. D.H. Hale. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  11. Administration of testosterone increases functional connectivity in a cortico-cortical depression circuit

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    Schutter, D.J.L.G.; Peper, J.S.; Koppeschaar, H.P.F.; Kahn, R.S.; Honk, E.J. van

    2005-01-01

    Increasing evidence suggests that the steroid hormone testosterone (T) enhances libido and decreases depression. Even a single administration of T (0.5 mg sublingually) in healthy young women is sufficient to enhance physiological sexual responsiveness. Such physiological evidence is not yet

  12. Exogenous testosterone decreases men's personal distance in a social threat context.

    Science.gov (United States)

    Wagels, Lisa; Radke, Sina; Goerlich, Katharina Sophia; Habel, Ute; Votinov, Mikhail

    2017-04-01

    Testosterone can motivate human approach and avoidance behavior. Specifically, the conscious recognition of and implicit reaction to angry facial expressions is influenced by testosterone. The study tested whether exogenous testosterone modulates the personal distance (PD) humans prefer in a social threat context. 82 healthy male participants underwent either transdermal testosterone (testosterone group) or placebo application (placebo group). Each participant performed a computerized stop-distance task before (T1) and 3.5h after (T2) treatment, during which they indicated how closely they would approach a human, animal or virtual character with varying emotional expression. Men's PD towards humans and animals varied as a function of their emotional expression. In the testosterone group, a pre-post comparison indicated that the administration of 50mg testosterone was associated with a small but significant reduction of men's PD towards aggressive individuals. Men in the placebo group did not change the initially chosen PD after placebo application independent of the condition. However comparing the testosterone and placebo group after testosterone administration did not reveal significant differences. While the behavioral effect was small and only observed as within-group effect it was repeatedly and selectively shown for men's PD choices towards an angry woman, angry man and angry dog in the testosterone group. In line with the literature, our findings in young men support the influential role of exogenous testosterone on male's approach behavior during social confrontations. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Cognitive effects of testosterone and finasteride administration in older hypogonadal men

    Directory of Open Access Journals (Sweden)

    Borst SE

    2014-08-01

    Full Text Available Stephen E Borst,1 Joshua F Yarrow,2 Carmen Fernandez,1 Christine F Conover,2 Fan Ye,2 John R Meuleman,1 Matthew Morrow,3 Baiming Zou,4 Jonathan J Shuster5 1Geriatric Research, Education and Clinical Center, 2Research Service, 3Pharmacy Service, Malcom Randall VA Medical Center, Gainesville Florida; 4Department of Biostatistics, 5Department of Health Outcomes and Policy, University of Florida, Gainesville, FL, USA Abstract: Serum concentrations of neuroactive androgens decline in older men and, in some ­studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor, in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥60 years with a serum testosterone concentration of ≤300 ng/dL or bioavailable testosterone ≤70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week versus vehicle, paired with finasteride (5 mg/day versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies

  14. Improvement of the diabetic foot upon testosterone administration to hypogonadal men with peripheral arterial disease. Report of three cases

    Directory of Open Access Journals (Sweden)

    Zemlyanoy Alexandr

    2009-03-01

    Full Text Available Abstract Background Lower extremity complications (neuropathy, ulceration, infection, and peripheral arterial disease are common in diabetes mellitus. There is an inverse relation between plasma testosterone and insulin sensitivity, type 2 diabetes mellitus and HbA1c concentrations. Methods We report the beneficial effects of administration of testosterone to three men with a diabetic foot whose serum testosterone was subnormal. Results Upon normalization of serum testosterone there was an improvement of hyperglycemia, a decrease of leukocytes and of fibrinogen levels, an increase of antithrombin III activity and of tissue oxygen pressure. The wound showed granulation. Conclusion Beneficial effects of administration of testosterone to hypogonadal with a diabetic foot may be due to improved vascularization and to anti-inflammatory action.

  15. Testosterone

    Science.gov (United States)

    ... to evaluate signs of abnormal testosterone such as: Early or late puberty (in boys) Infertility, erectile dysfunction, low level of ... brain that control hormones Low thyroid function Delayed ... much body fat (obesity) Increased total testosterone level may be due to: ...

  16. Testosterone Administration Inhibits Hepcidin Transcription and is Associated with Increased Iron Incorporation into Red Blood Cells

    Science.gov (United States)

    Guo, Wen; Bachman, Eric; Li, Michelle; Roy, Cindy N.; Blusztajn, Jerzy; Wong, Siu; Chan, Stephen Y.; Serra, Carlo; Jasuja, Ravi; Travison, Thomas G.; Muckenthaler, Martina U.; Nemeth, Elizabeta; Bhasin, Shalender

    2013-01-01

    Testosterone administration increases hemoglobin levels and has been used to treat anemia of chronic disease. Erythrocytosis is the most frequent adverse event associated with testosterone therapy of hypogonadal men, especially older men. However, the mechanisms by which testosterone increases hemoglobin remain unknown. Testosterone administration in male and female mice was associated with a greater increase in hemoglobin and hematocrit, reticulocyte count, reticulocyte hemoglobin concentration, and serum iron and transferring saturation than placebo. Testosterone downregulated hepatic hepcidin mRNA expression, upregulated renal erythropoietin mRNA expression, and increased erythropoietin levels. Testosterone-induced suppression of hepcidin expression was independent of its effects on erythropoietin or hypoxia-sensing mechanisms. Transgenic mice with liver-specific constitutive hepcidin over-expression failed to exhibit the expected increase in hemoglobin in response to testosterone administration. Testosterone upregulated splenic ferroportin expression and reduced iron retention in spleen. After intravenous administration of transferrin-bound 58Fe, the amount of 58Fe incorporated into red blood cells was significantly greater in testosterone-treated mice than in placebo-treated mice. Serum from testosterone-treated mice stimulated hemoglobin synthesis in K562 erythroleukemia cells more than that from vehicle-treated mice. Testosterone administration promoted the association of androgen receptor (AR) with Smad1 and Smad4 to reduce their binding to BMP-response elements in hepcidin promoter in the liver. Ectopic expression of AR in hepatocytes suppressed hepcidin transcription; this effect was blocked dose-dependently by AR antagonist flutamide. Testosterone did not affect hepcidin mRNA stability. Conclusion: Testosterone inhibits hepcidin transcription through its interaction with BMP-Smad signaling. Testosterone administration is associated with increased iron

  17. Rosuvastatin decreases testosterone levels but not sexual function in men with type 2 diabetes.

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    Hsieh, Ching Jung; Huang, Bin

    2016-10-01

    Statins may decrease serum testosterone levels via decreasing cholesterol, a precursor to testosterone. This case series studied the effects of rosuvastatin on free testosterone levels and sexual function in men with type 2 diabetes. We enrolled 151 men with type 2 diabetes and hypercholesterolemia. Biochemical assessments included serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, prolactin, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone, total testosterone and serum sex hormone binding globulin (SHBG). All parameters were measured before statin treatment, after 6months of statin treatment, and 6months after discontinuing statin treatment. The Sexual Health Inventory for Men (SHIM) was also administered at these times. Serum TC and LDL levels were high before statin therapy, decreased after six months of statin therapy, and increased significantly six months after discontinuing statin therapy (198.1±28.1mg/dl vs. 147.1±22.8mg/dl vs. 205.2±25.6mg/dl, p-valuefree testosterone levels calculated from total testosterone and SHBG calculated by formula were higher before statin therapy, obviously decreased after six months of statin therapy, and subsequently increased six months after discontinuing statin therapy (22.4±3.1ng/ml vs. 20.9±2.8ng/ml vs. 22.6±2.6ng/ml p value=0.006). SHIM scores did not obviously differ among the three stages (16.3±4.8 vs. 16.0±4.9 vs. 16.3±5.0 p=0.944). After adjustment for age, serum free testosterone levels correlated with SHIM scores and LDL (r=0.39, p=free testosterone levels but does not influence sexual function in men with type 2 diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. The Effect of Castration and Testosterone Administration on ...

    African Journals Online (AJOL)

    SOS

    2012-04-18

    Apr 18, 2012 ... To study the effect of castration and testosterone replacement on the testosterone level of the New. Zealand rabbit, 16 apparently ... After two weeks, the rabbits were castrated and the effect of castration and ... infiltration of the local anesthetic around the neck of scrotum (Hall,. 1979). Each testicle was then ...

  19. The effects of chronic testosterone administration on body weight, food intake, and adipose tissue are changed by estrogen treatment in female rats.

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    Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Yanagihara, Rie; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Mayila, Yiliyasi; Kuwahara, Akira; Irahara, Minoru

    2017-07-01

    In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats. In addition, chronic testosterone administration increased hypothalamic CYP19a1 mRNA levels in OVX rats, whereas it did not alter CYP19a1 mRNA levels in OVX with estradiol-administered rats, indicating that conversion of testosterone to estrogens in the hypothalamus may be activated in testosterone-administered OVX rats. Furthermore, chronic testosterone administration decreased hypothalamic TNF-α mRNA levels in OVX rats, whereas it increased hypothalamic IL-1β mRNA levels in OVX with estradiol-administered rats. On the other hand, IL-1β and TNF-α mRNA levels in visceral and subcutaneous WAT and liver were not changed by chronic testosterone administration in both groups. These data indicate that the effects of chronic testosterone administration on BW, FI, WAT weight, and adipocyte size were changed by estradiol treatment in female rats. Testosterone has facilitative effects on BW gain, FI, and adiposity under the estradiol-supplemented condition, whereas it has inhibitory effects in the non-supplemented condition. Differences in the responses of hypothalamic factors, such as aromatase and inflammatory cytokines, to testosterone might underlie these opposite effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Oxytocin administration, salivary testosterone, and father-infant social behavior.

    Science.gov (United States)

    Weisman, Omri; Zagoory-Sharon, Orna; Feldman, Ruth

    2014-03-03

    The growing involvement of fathers in childcare is followed by an increased interest in the neurobiology of fatherhood; yet, experimental work on the neuroendocrine basis of paternal care in humans is limited. The steroid Testosterone (T) and the neuropeptide Oxytocin (OT) have each been implicated in complex social behavior including parenting. However, no study to date explored the interaction between these two hormones in the context of fathering. In the current study we first test the relationship between father's basal salivary T and father and infant's social behaviors during parent-child interaction. Second, we examine the effects of intranasal OT administration on father's T production, and, finally, address the relations between OT-induced change in father's T with father-infant social behavior. Thirty-five fathers and their infants participated in a double-blind, placebo-controlled, within-subject study. Father-infant interaction was micro-coded for paternal and infant social behavior and synchrony was measured as the coordination between their gaze, affect, and vocalizations. Father's salivary T levels were measured at baseline and three times after administration. Results indicate that lower baseline T correlated with more optimal father and infant's behaviors. OT administration altered T production in fathers, relative to the pattern of T in the placebo condition. Finally, OT-induced change in T levels correlated with parent-child social behaviors, including positive affect, social gaze, touch, and vocal synchrony. Findings support the view that neuroendocrine systems in human males evolved to support committed parenting and are the first to describe the dynamic interactions between OT and T within a bio-behavioral synchrony model. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Effects of Testosterone Administration on Strategic Gambling in Poker Play

    NARCIS (Netherlands)

    van Honk, Jack|info:eu-repo/dai/nl/188602801; Will, Geert-Jan; Terburg, David|info:eu-repo/dai/nl/32304087X; Raub, Werner|info:eu-repo/dai/nl/07031764X; Eisenegger, Christoph; Buskens, Vincent|info:eu-repo/dai/nl/181299313

    2016-01-01

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans,

  2. Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals

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    Giuseppe Loverro

    2016-10-01

    Conclusion: Our data suggest that long-term testosterone administration to female-to-male patients during reproductive age induces a low proliferative active endometrium, associated with some hypertrophic myometrial changes.

  3. Paradoxical sleep deprivation decreases serum testosterone and Leydig cells in male rats

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    Fitranto Arjadi

    2014-04-01

    Full Text Available Background Chronic stress increases glucocorticoid levels and accelerates reduction in Leydig cells functions and numbers. Chronic stress models in the working place comprise sleep deprivation, sedentary stress, and physical stress. The aim of this study was to evaluate the effect of various work stress models, such as stress from paradoxical sleep deprivation (PSD, immobilization, and footshock, on serum testosterone levels and number of Leydig cells in male albino rats. Methods This study was of experimental randomized post-test only with control group design using 24 male Wistar albino rats (Rattus norvegicus. The sample was divided into 4 groups: K1 (control, K2 (PSD, K3 (immobilization and K4 (footshock, receiving treatment for 25 days. Measured parameters were serum testosterone level and Leydig cell number. Analysis of variance (ANOVA was used for statistical analysis, followed by post hoc LSD. Results Mean serum testosterone levels (0.07 ± 0.08 ng/mL and Leydig cell numbers (4.22 ± l0.96 were lowest in the PSD stress model. Serum testosterone levels differed significantly between controls and PSD group (p=0.014, while there was a significant difference in numbers of Leydig cells between footshock stress and PSD (p=0.011 and between the three stress groups and controls (p=0.006. Conclusion This study demonstrated that PSD, immobilization and footshock stress significantly decreased serum testosterone levels and number of Leydig cells in male albino rats (Rattus norvegicus. The mechanism by which PSD affects serum testosterone is still unclear.

  4. Paradoxical sleep deprivation decreases serum testosterone and Leydig cells in male rats

    Directory of Open Access Journals (Sweden)

    Fitranto Arjadi

    2015-12-01

    Full Text Available BACKGROUND Chronic stress increases glucocorticoid levels and accelerates reduction in Leydig cells functions and numbers. Chronic stress models in the working place comprise sleep deprivation, sedentary stress, and physical stress. The aim of this study was to evaluate the effect of various work stress models, such as stress from paradoxical sleep deprivation (PSD, immobilization, and footshock, on serum testosterone levels and number of Leydig cells in male albino rats. METHODS This study was of experimental randomized post-test only with control group design using 24 male Wistar albino rats (Rattus norvegicus. The sample was divided into 4 groups: K1 (control, K2 (PSD, K3 (immobilization and K4 (footshock, receiving treatment for 25 days. Measured parameters were serum testosterone level and Leydig cell number. Analysis of variance (ANOVA was used for statistical analysis, followed by post hoc LSD. RESULTS Mean serum testosterone levels (0.07 ± 0.08 ng/ml and Leydig cell numbers (4.22 ± l0.96 were lowest in the PSD stress model. Serum testosterone levels differed significantly between controls and PSD group (p=0.014, while there was a significant difference in numbers of Leydig cells between footshock stress and PSD (p=0.011 and between the three stress groups and controls (p=0.006. CONCLUSION This study demonstrated that PSD, immobilization and footshock stress significantly decreased serum testosterone levels and number of Leydig cells in male albino rats (Rattus norvegicus. The mechanism by which PSD affects serum testosterone is still unclear.

  5. The effect of parenteral testosterone administration prior to hypospadias surgery: A prospective, randomized and controlled study.

    Science.gov (United States)

    Asgari, S A; Safarinejad, M R; Poorreza, F; Asl, A Safaei; Ghanaie, M Mansour; Shahab, E

    2015-06-01

    .1 ± 1.6 mm to 45.5 ± 2.2 mm) (P = 0.001) were noticed in all but four children in Group 1. The actual values for increase in penile length in the study group were, 22.0%, 35.0% and 36.0%, at postinjection months 1, 2 and 3, respectively (P = 0.01, P = 0.001 and P = 0.001, respectively) (Figure). The actual values for increase in penile circumference in the study group were, 16.0%, 27.0% and 29.0%, at postinjection months 1, 2 and 3, respectively (P=0.01, P=0.001 and P =0.001, respectively). The overall complication rates were significantly higher in Group 2 [12 children, 13.18%) compared to Group 1 (five children, 5.45%) (P=0.03). Urethrocutaneous fistula was the most common complication in both groups (four children [4.39%] in Group 1 and seven children [7.69%] in Group 2) (P=0.02), followed by meatal stenosis (one child [1.09%] in Group 1 and three children [3.29%] in Group 2) (P=0.03). All children in Group 1 developed pigmentation of the genitalia, and scant pubic hair appeared in 14 of them. These side effects disappeared by the 3 months postoperation follow-up visit. Tubularized incised plate urethroplasty is a popular reconstructive method for hypospadias repair and is widely accepted by pediatric urologists. It is a reliable and simple technique with low complication rates. Testosterone administration before hypospadias repair decreases complication rates, reduces the need for reoperation and results in better cosmetic outcomes. Some studies have demonstrated temporary side effects like pubic hair growth and aggressive behavior, which gradually became normalized after treatment cessation. Nowadays, many pediatric urologists administer testosterone prior to hypospadias surgery; however, this can be variable. Parenteral testosterone administration before hypospadias repair is beneficial in decreasing complication rates. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  6. Testosterone administration related differences in brain activation during the Ultimatum Game

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    Eleni eKopsida

    2016-03-01

    Full Text Available A plethora of studies on the Ultimatum Game have shown that responders forfeit the rule of profit maximization and punish unfair proposers, by rejecting their offers. This behavior has been linked to increased amygdala, insula and dorsolateral prefrontal cortex activation. Studies have suggested a potential role of testosterone in the Ultimatum Game albeit with inconsistent findings. In the present study, we sought to further investigate the role of amygdala and testosterone in the Ultimatum Game, by conducting a double-blinded, single-administration study. 60mg of Tostrex was administered to male and female healthy volunteers, three hours prior to undergoing an fMRI session, during which they played a standard version of the Ultimatum Game. The behavioral analysis revealed a statistical trend, as participants in the testosterone group tended to accept a greater number of unfair offers than participants in the placebo group, irrespectively of gender. In terms of fMRI results, for the main contrast unfair>fair offers, the testosterone group displayed a greater activation in the right dlPFC compared to the placebo group. Increased testosterone levels were related to greater caudate activity. Our findings suggest a complex role of testosterone in social behavior and decision-making.

  7. Muscles of the trunk and pelvis are responsive to testosterone administration: data from testosterone dose-response study in young healthy men.

    Science.gov (United States)

    Tapper, J; Arver, S; Pencina, K M; Martling, A; Blomqvist, L; Buchli, C; Li, Z; Gagliano-Jucá, T; Travison, T G; Huang, G; Storer, T W; Bhasin, S; Basaria, S

    2018-01-01

    Testosterone dose-dependently increases appendicular muscle mass. However, the effects of testosterone administration on the core muscles of the trunk and the pelvis have not been evaluated. The present study evaluated the effects of testosterone administration on truncal and pelvic muscles in a dose-response trial. Participants were young healthy men aged 18-50 years participating in the 5α-Reductase (5aR) Trial. All participants received monthly injections of 7.5 mg leuprolide acetate to suppress endogenous testosterone production and weekly injections of 50, 125, 300, or 600 mg of testosterone enanthate and were randomized to receive either 2.5 mg dutasteride (5aR inhibitor) or placebo daily for 20 weeks. Muscles of the trunk and the pelvis were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The dose effect of testosterone on changes in the psoas major muscle area was the primary outcome; secondary outcomes included changes in paraspinal, abdominal, pelvic floor, ischiocavernosus, and obturator internus muscles. The association between changes in testosterone levels and muscle area was also assessed. Testosterone dose-dependently increased areas of all truncal and pelvic muscles. The estimated change (95% confidence interval) of muscle area increase per 100 mg of testosterone enanthate dosage increase was 0.622 cm2 (0.394, 0.850) for psoas; 1.789 cm2 (1.317, 2.261) for paraspinal muscles, 2.530 cm2 (1.627, 3.434) for total abdominal muscles, 0.455 cm2 (0.233, 0.678) for obturator internus, and 0.082 cm2 (0.003, 0.045) for ischiocavernosus; the increase in these volumes was significantly associated with the changes in on-treatment total and free serum testosterone concentrations. In conclusion, core muscles of the trunk and pelvis are responsive to testosterone administration. Future trials should evaluate the potential role of testosterone administration in frail men who are predisposed to falls and men with

  8. Effect of Testosterone Administration on Liver Fat in Older Men With Mobility Limitation: Results From a Randomized Controlled Trial

    Science.gov (United States)

    2013-01-01

    Background. Androgen receptor (AR) knockout male mice display hepatic steatosis, suggesting that AR signaling may regulate hepatic fat. However, the effects of testosterone replacement on hepatic fat in men are unknown. The aim of this study was to determine the effects of testosterone administration on hepatic fat in older men with mobility limitation and low testosterone levels who were participating in a randomized trial (the Testosterone in Older Men trial). Methods. Two hundred and nine men with mobility limitation and low total or free testosterone were randomized in the parent trial to either placebo or 10-g testosterone gel daily for 6 months. Hepatic fat was determined by magnetic resonance imaging in 73 men (36 in placebo and 37 in testosterone group) using the volumetric method. Insulin sensitivity (homeostatic model assessment–insulin resistance) was derived from fasting glucose and insulin. Results. Baseline characteristics were similar between the two groups, including liver volumes (1583±363 in the testosterone group vs 1522±271mL in the placebo group, p = .42). Testosterone concentrations increased from 250±72 to 632±363ng/dL in testosterone group but did not change in placebo group. Changes in liver volume during intervention did not differ significantly between groups (p = .5) and were not related to on-treatment testosterone concentrations. The change in homeostatic model assessment–insulin resistance also did not differ significantly between groups and was not related to either baseline or change in liver fat. Conclusion. Testosterone administration in older men with mobility limitation and low testosterone levels was not associated with a reduction in hepatic fat. Larger trials are needed to determine whether testosterone replacement improves liver fat in men with nonalcoholic hepatic steatosis. PMID:23292288

  9. Combined administration of testosterone plus an ornithine decarboxylase inhibitor as a selective prostate-sparing anabolic therapy.

    Science.gov (United States)

    Jasuja, Ravi; Costello, James C; Singh, Rajan; Gupta, Vandana; Spina, Catherine S; Toraldo, Gianluca; Jang, Hyeran; Li, Hu; Serra, Carlo; Guo, Wen; Chauhan, Pratibha; Narula, Navjot S; Guarneri, Tyler; Ergun, Ayla; Travison, Thomas G; Collins, James J; Bhasin, Shalender

    2014-04-01

    Because of its anabolic effects on muscle, testosterone is being explored as a function-promoting anabolic therapy for functional limitations associated with aging; however, concerns about testosterone's adverse effects on prostate have inspired efforts to develop strategies that selectively increase muscle mass while sparing the prostate. Testosterone's promyogenic effects are mediated through upregulation of follistatin. We show here that the administration of recombinant follistatin (rFst) increased muscle mass in mice, but had no effect on prostate mass. Consistent with the results of rFst administration, follistatin transgenic mice with constitutively elevated follistatin levels displayed greater muscle mass than controls, but had similar prostate weights. To elucidate signaling pathways regulated differentially by testosterone and rFst in prostate and muscle, we performed microarray analysis of mRNAs from prostate and levator ani of castrated male mice treated with vehicle, testosterone, or rFst. Testosterone and rFst shared the regulation of many transcripts in levator ani; however, in prostate, 593 transcripts in several growth-promoting pathways were differentially expressed after testosterone treatment, while rFst showed a negligible effect with only 9 transcripts differentially expressed. Among pathways that were differentially responsive to testosterone in prostate, we identified ornithine decarboxylase (Odc1), an enzyme in polyamine biosynthesis, as a testosterone-responsive gene that is unresponsive to rFst. Accordingly, we administered testosterone with and without α-difluoromethylornithine (DFMO), an Odc1 inhibitor, to castrated mice. DFMO selectively blocked testosterone's effects on prostate, but did not affect testosterone's anabolic effects on muscle. Co-administration of testosterone and Odc1 inhibitor presents a novel therapeutic strategy for prostate-sparing anabolic therapy. © 2013 The Authors. Aging Cell published by the Anatomical

  10. Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration.

    Science.gov (United States)

    Huang, Grace; Pencina, Karol M; Coady, Jeffry A; Beleva, Yusnie M; Bhasin, Shalender; Basaria, Shehzad

    2015-06-01

    To determine dose-dependent effects of T administration on voice changes in women with low T levels. Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics. Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed. Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice.

  11. Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration

    Science.gov (United States)

    Pencina, Karol M.; Coady, Jeffry A.; Beleva, Yusnie M.; Bhasin, Shalender; Basaria, Shehzad

    2015-01-01

    Objective: To determine dose-dependent effects of T administration on voice changes in women with low T levels. Methods: Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics. Results: Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed. Conclusion: Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice. PMID:25875779

  12. Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

    Science.gov (United States)

    Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

  13. Acute decrease in serum testosterone after a mixed glucose and protein beverage in obese peripubertal boys.

    Science.gov (United States)

    Schwartz, Alexander; Patel, Barkha P; Vien, Shirley; McCrindle, Brian W; Anderson, G Harvey; Hamilton, Jill

    2015-09-01

    Delayed puberty and lower levels of testosterone (T) have been observed in adult obese males and some adolescent males. In adult men, enteral glucose ingestion results in acute lowering of serum testosterone levels; however, this has not been studied in adolescents. We aimed to examine the acute effect of a glucose/protein beverage on serum T concentration changes in obese peripubertal males. A second objective was to determine whether change in T concentration was related to appetite hormone levels. Twenty-three overweight and obese males aged 8-17 in pre-early (Tanner stage 1-2) and mid-late (Tanner stage 3-5) puberty were included in this cross-sectional study at the Clinical investigative unit at the Hospital for Sick Children. Participants consumed a beverage containing glucose and protein, and blood samples measuring pubertal hormones, ghrelin and glucagon-like peptide-1 (GLP-1) were taken over 60 min. Across pubertal stages, there was a significant decrease in T levels in adolescent boys (-18·6 ± 3·1%, P early and mid-late puberty (P = 0·09). Decrease in T was associated with a decrease in LH (r = 0·52, P = 0·02), and fasting T was inversely correlated with fasting ghrelin (r = -0·51, P = 0·03) with no correlation with GLP-1. Intake of a mixed glucose/protein beverage acutely decreases T levels in overweight and obese peripubertal boys. A potential mechanism for this decrease may be secondary to an acute decrease in LH, but this requires further evaluation. © 2014 John Wiley & Sons Ltd.

  14. Effects of co-administration of clenbuterol and testosterone propionate on skeletal muscle in paraplegic mice.

    Science.gov (United States)

    Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

    2010-06-01

    Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.

  15. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation

    DEFF Research Database (Denmark)

    Rasmussen, Jon Jarløv; Selmer, Christian; Østergren, Peter Busch

    2016-01-01

    AIMS: 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. METHODS: This st......AIMS: 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. METHODS...... 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. RESULTS: Former AAS abusers...

  16. Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress.

    Science.gov (United States)

    Cruz, Fábio C; Engi, Sheila A; Leão, Rodrigo M; Planeta, Cleopatra S; Crestani, Carlos C

    2012-10-01

    Abuse of cocaine and androgenic-anabolic steroids (AASs) has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous abuse of these substances, potential toxic interactions between cocaine and AASs are poorly known. In the present study, we investigated the effects of either single or combined administration of testosterone and cocaine for one or 10 consecutive days on autonomic (arterial pressure, heart rate and tail cutaneous temperature) and neuroendocrine (plasma corticosterone) responses induced by acute restraint stress in rats. Combined administration of testosterone and cocaine for 10 days reduced the increase in heart rate and plasma corticosterone level, as well as the fall in tail skin temperature induced by restraint stress. Furthermore, repeated administration of cocaine inhibited the increase in arterial pressure observed during restraint, and this effect was not affected by coadministration of testosterone. Ten-day combined administration of testosterone and cocaine increased basal values of arterial pressure. Moreover, chronic administration of testosterone induced rest bradycardia and elevated basal level of plasma corticosterone. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present study demonstrated that combined administration of testosterone and cocaine changed the autonomic and neuroendocrine responses to acute restraint stress. These findings suggest that interaction between AASs and cocaine may affect the ability to cope with stressful events.

  17. Effect of Urtica Dioica Extract on Histological and Histometrical Changes of Testis of Hamster after Testosteron Administration

    Directory of Open Access Journals (Sweden)

    Hassan Morovvati

    2013-11-01

    Full Text Available Background: Hyperactivity of testosterone is one cause of infertility and its incorrect use can produces reproductive disorders. Nettle (Urtica dioica has antiandrogenic effect and may antagonized effect of testosterone. In present study structure of testes of golden hamster was evaluated after testosterone and extract. Materials and Methods: In this experimental and animal modeling study, twenty male mature hamsters were divided to 4 groups, group 1 was control, group 2 received testosterone at dose 3 mg/kg subcutaneously, group 3 received nettle extract dose 30 mg/kg orally and group 4 received testosterone and nettle for 30 days daily. The hamsters were euthanized and testes were removed and detected macroscopic parameters (weight, height, wide and volume and fixed with formalin. The samples were sectioned and colored with H & E. Results: The volume, weight, length and wide of testes was at least in testosterone group and statistically was lesser than control and testosterone -nettle group (p<0.05, but did not the height epithelium of seminifer tubules, compact of spermatogenic cells and number of serotolli cells in testosterone group was lesser than control group significantly (p<0.05.Conclusion: The nettle extract decreased histological changes of testes by testosterone and improved its structure.

  18. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial.

    Science.gov (United States)

    Borst, Stephen E; Yarrow, Joshua F; Conover, Christine F; Nseyo, Unyime; Meuleman, John R; Lipinska, Judyta A; Braith, Randy W; Beck, Darren T; Martin, Jeffrey S; Morrow, Matthew; Roessner, Shirley; Beggs, Luke A; McCoy, Sean C; Cannady, Darryl F; Shuster, Jonathan J

    2014-02-15

    Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue.

  19. Effect of the single or combined administration of cocaine and testosterone on cardiovascular function and baroreflex activity in unanesthetized rats.

    Science.gov (United States)

    Engi, Sheila A; Cruz, Fábio C; Leão, Rodrigo M; Corrêa, Fernando M; Planeta, Cleopatra S; Crestani, Carlos C

    2012-03-01

    Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

  20. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease.

    Science.gov (United States)

    Ziehn, Marina O; Avedisian, Andrea A; Dervin, Shannon M; Umeda, Elizabeth A; O'Dell, Thomas J; Voskuhl, Rhonda R

    2012-09-05

    Over 50% of multiple sclerosis (MS) patients experience cognitive deficits, and hippocampal-dependent memory impairment has been reported in >30% of these patients. While postmortem pathology studies and in vivo magnetic resonance imaging demonstrate that the hippocampus is targeted in MS, the neuropathology underlying hippocampal dysfunction remains unknown. Furthermore, there are no treatments available to date to effectively prevent neurodegeneration and associated cognitive dysfunction in MS. We have recently demonstrated that the hippocampus is also targeted in experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS. The objective of this study was to assess whether a candidate treatment (testosterone) could prevent hippocampal synaptic dysfunction and underlying pathology when administered in either a preventative or a therapeutic (postdisease induction) manner. Electrophysiological studies revealed impairments in basal excitatory synaptic transmission that involved both AMPA receptor-mediated changes in synaptic currents, and faster decay rates of NMDA receptor-mediated currents in mice with EAE. Neuropathology revealed atrophy of the pyramidal and dendritic layers of hippocampal CA1, decreased presynaptic (Synapsin-1) and postsynaptic (postsynaptic density 95; PSD-95) staining, diffuse demyelination, and microglial activation. Testosterone treatment administered either before or after disease induction restores excitatory synaptic transmission as well as presynaptic and postsynaptic protein levels within the hippocampus. Furthermore, cross-modality correlations demonstrate that fluctuations in EPSPs are significantly correlated to changes in postsynaptic protein levels and suggest that PSD-95 is a neuropathological substrate to impaired synaptic transmission in the hippocampus during EAE. This is the first report demonstrating that testosterone is a viable therapeutic treatment option that can restore both hippocampal

  1. Testosterone Test

    Science.gov (United States)

    ... Related Content View Sources Also Known As Total Testosterone Free Testosterone Bioavailable Testosterone Formal Name Testosterone This article ... small percent (less than 4%) circulates as free testosterone. Free testosterone plus the testosterone bound to albumin is ...

  2. Post-partum testosterone administration partially reverses the effects of perinatal cadmium exposure on sexual behavior in rats

    OpenAIRE

    Couto-Moraes, Renato; Felício, Luciano Freitas; Oliveira, Claudio Alvarenga de; Bernardi, Maria Martha

    2012-01-01

    This study investigated the effects of perinatal cadmium exposure on sexual behavior, organ weight, and testosterone levels in adult rats. We examined whether immediate postpartum testosterone administration is able to reverse the toxic effects of the metal. Forty pregnant Wistar rats were divided into three groups: 1) control, 2) 10 mg kg-1 cadmium chloride per day, and 3) 20 mg kg-1 cadmium chloride per day. These dams were treated on gestational days 18 and 21 and from lactation 1 to 7. Im...

  3. Testosterone administration in women increases amygdala responses to fearful and happy faces

    NARCIS (Netherlands)

    Bos, P.A.; Honk, J. van; Ramsey, N.F.; Stein, D.J.; Hermans, E.J.

    2013-01-01

    Data from both rodents and humans show that testosterone reduces fear. This effect is hypothesized to result from testosterone's down regulating effects on the amygdala, a key region in the detection of threat and instigator of fight-or-flight behavior. However, neuroimaging studies employing

  4. Testosterone Therapy: Review of Clinical Applications.

    Science.gov (United States)

    Petering, Ryan C; Brooks, Nathan A

    2017-10-01

    Testosterone therapy is increasingly common in the United States, and many of these prescriptions are written by primary care physicians. There is conflicting evidence on the benefit of male testosterone therapy for age-related declines in testosterone. Physicians should not measure testosterone levels unless a patient has signs and symptoms of hypogonadism, such as loss of body hair, sexual dysfunction, hot flashes, or gynecomastia. Depressed mood, fatigue, decreased strength, and a decreased sense of vitality are less specific to male hypogonadism. Testosterone therapy should be initiated only after two morning total serum testosterone measurements show decreased levels, and all patients should be counseled on the potential risks and benefits before starting therapy. Potential benefits of therapy include increased libido, improved sexual function, improved mood and well-being, and increased muscle mass and bone density; however, there is little or mixed evidence confirming clinically significant benefits. The U.S. Food and Drug Administration warns that testosterone therapy may increase the risk of cardiovascular complications. Other possible risks include rising prostate-specific antigen levels, worsening lower urinary tract symptoms, polycythemia, and increased risk of venous thromboembolism. Patients receiving testosterone therapy should be monitored to ensure testosterone levels rise appropriately, clinical improvement occurs, and no complications develop. Testosterone therapy may also be used to treat hypoactive sexual desire disorder in postmenopausal women and to produce physical male sex characteristics in female-to-male transgender patients.

  5. Sensitivity of doping biomarkers after administration of a single dose testosterone gel.

    Science.gov (United States)

    Mullen, Jenny; Börjesson, Annica; Hopcraft, Oscar; Schulze, Jenny J; Ericsson, Magnus; Rane, Anders; Lehtihet, Mikael; Ekström, Lena

    2017-11-18

    Micro-doping with testosterone (T) is challenging to detect with the current doping tests. Today, the methods available to detect T are longitudinally monitoring of urine biomarkers in the Athlete Biological Passport (ABP) and measuring the isotopic composition of excreted biomarkers to distinguish the origin of the molecule. In this study, we investigated the detectability of a single dose of 100 mg T gel in 8 healthy male subjects. We also studied which biomarkers were most sensitive to T gel administration, including blood biomarkers. The ABP successfully detected T gel administration in all 8 subjects. The most sensitive ratio was 5αAdiol/E, however, also T/E and 5αAdiol/5βAdiol showed atypical findings. IRMS was performed on 5 subjects and only two met all the criteria for a positive test according to the rules set by WADA. The other three showed inconclusive results. Other markers that were affected by T gel administration, not used for this detection today, were serum dihydrotestosterone (DHT) and T as well as reticulocyte count and percentage in whole blood. miRNA-122 was not significantly affected by the single T dose. A single dose of 100 mg T gel is possible to detect with today's doping tests. Since a single dose of T gel has an impact on some hematological biomarkers, access to both modules of the ABP when evaluating the athletes' profiles will increase the possibility to detect micro-doses of T. In addition, serum DHT and T may be a useful addition to the future endocrine module of the biological passport. This article is protected by copyright. All rights reserved.

  6. Ethanol does not delay muscle recovery but decreases testosterone/cortisol ratio.

    Science.gov (United States)

    Haugvad, Anders; Haugvad, Lars; Hamarsland, Håvard; Paulsen, Gøran

    2014-11-01

    This study investigated the effects of ethanol consumption on recovery from traditional resistance exercise in recreationally trained individuals. Nine recreationally trained volunteers (eight males and one female, 26 ± 4 yr, 81 ± 4 kg) conducted four resistance exercise sessions and consumed a low (0.6 (females) and 0.7 (males) g · kg(-1) body mass) or a high dose (1.2 or 1.4 g · kg(-1) body mass) of ethanol 1-2.5 h after exercise on two occasions. The first session was for familiarization with the tests and exercises and was performed without ethanol consumption. As a control trial, alcohol-free drinks were consumed after the exercise session. The sequence of trials, with low and high ethanol doses and alcohol-free drinks (control), was randomized. Maximal voluntary contractions (MVC) (knee extension), electrically stimulated contractions (knee extension), squat jumps, and hand grip strength were assessed 10-15 min and 12 and 24 h after the ethanol/placebo drinks. In addition to a baseline sample, blood was collected 1, 12, and 24 h after the ethanol/placebo drinks. The exercise session comprised 4 × 8 repetition maximum of squats, leg presses, and knee extensions. MVC were reduced by 13%-15% immediately after the exercise sessions (P < 0.01). MVC, electrically stimulated force, and squat jump performance were recovered 24 h after ethanol drinks. MVC was not fully recovered at 24 h in the control trial. Compared with those in the control, cortisol increased and the free testosterone/cortisol ratio were reduced after the high ethanol dose (P < 0.01). Neither a low nor a high dose of ethanol adversely affected recovery of muscle function after resistance exercise in recreationally strength-trained individuals. However, the increased cortisol levels and reduced testosterone/cortisol ratio after the high ethanol dose could translate into long-term negative effects.

  7. Testosterone Injection

    Science.gov (United States)

    ... and testosterone pellet (Testopel) are forms of testosterone injection used to treat symptoms of low testosterone in ... are low before you begin to use testosterone injection. Testosterone enanthate (Delatestryl) and testosterone pellet (Testopel) are ...

  8. Post-partum testosterone administration does not reverse the effects of perinatal exposure to cadmium on rat offspring development.

    Science.gov (United States)

    Couto-Moraes, R; Felicio, L F; Bernardi, M M

    2010-04-01

    This study investigated the effects of perinatal cadmium exposure on physical and reflexologic development of pup rats. It was examined if the immediate postpartum testosterone administration was able to reverse the toxic effects of the metal. Forty Wistar pregnant rats were divided into three groups: control and 10 and 20 mg kg(-1) per day of cadmium chloride. These dams were treated from gestational days 18 to 21, and until the 7th lactation day. Immediately after birth, half of the offspring from the experimental and control groups received 50 microL of testosterone 0.2% i.p. The maternal body weight gain, food and water consumption were measured during the treatment period. In pups, the body weight, body length, physical landmarks, reflex development and the general activity were assessed. Results showed that: only 20 mg kg(-1) cadmium induced maternal toxicity; pup body weight and body weight gain were reduced in all experimental groups; only the cadmium-exposed offspring not treated with testosterone treatment showed a reduction in body length and body length gain; cadmium highest dose reduced the anogenital index in pups and delayed physical and reflexes development; and cadmium effects on the offspring, except in body length gain, were not reversed by testosterone. The results indicate that perinatal maternal exposure to cadmium promoted changes in the development of male rat offspring, reprogramming the pup's development. Testosterone administration was not able to reverse the cadmium effects, even on those parameters more directly related to the androgenic system as the testis descent and anogenital distance delays. (c) 2009 John Wiley & Sons, Ltd.

  9. Osteoprotegerin Levels Decrease During Testosterone Therapy in Aging Men and are Associated with Changed Distribution of Regional Fat

    DEFF Research Database (Denmark)

    Frederiksen, L; Glintborg, D; Højlund, K

    2013-01-01

    The cardiovascular effects of testosterone treatment are debated. Osteoprotegerin (OPG) is an independent marker of cardiovascular risk. We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels. A randomized, double......-blinded, placebo-controlled study of 6 months testosterone therapy (gel) in 38 men aged 60-78 years with bioavailable testosterone 94 cm was performed. Clinical evaluation, OPG, and C-reactive protein (CRP) measurements were carried out. Lean body mass (LBM), total fat mass, and bone mineral density (BMD) were...... established by dual X-ray absorptiometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by magnetic resonance imaging. Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased...

  10. Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial.

    Science.gov (United States)

    Huang, Grace; Wharton, Whitney; Bhasin, Shalender; Harman, S Mitchell; Pencina, Karol M; Tsitouras, Panayiotis; Li, Zhuoying; Hally, Kathleen A; Asthana, Sanjay; Storer, Thomas W; Basaria, Shehzad

    2016-08-01

    The effects of testosterone on cognitive function in older men are incompletely understood. We aimed to establish the effects of long-term testosterone administration on multiple domains of cognitive function in older men with low or low-to-normal testosterone concentrations. We did the randomised, double-blind, placebo-controlled, parallel-group TEAAM trial at three medical centres in Boston, Phoenix, and Los Angeles, USA. Men aged 60 years and older with low or low-to-normal testosterone concentrations (3·47-13·9 nmol/L, or free testosterone testosterone gel or placebo gel daily for 3 years. Randomisation was stratified by age (60-75 years vs >75 years) and study site. The testosterone dose was adjusted to achieve concentrations of 17·3-31·2 nmol/L. Participants and all study personnel were masked to treatment allocation. Multiple domains of cognitive function were assessed as prespecified secondary outcomes by use of standardised tests at baseline and months 6, 18, and 36. We did analyses by intention to treat (in men who had baseline assessments of cognitive function) and per protocol (restricted to participants who completed the study drug and had both baseline and 36 month assessments of cognitive function). The TEAAM trial is registered with ClinicalTrials.gov, number NCT00287586. Between Sept 1, 2004, and Feb 12, 2009, we randomly assigned 308 participants to receive either testosterone (n=156) or placebo (n=152). 280 men had baseline cognitive assessments (n=140 per group). Mean follow-up time was 29·0 months (SD 11·5) in the testosterone group and 31·1 months (9·5) in the placebo group. The last participant completed the study on May 11, 2012. In the testosterone group, mean concentrations of serum total testosterone increased from 10·6 nmol/L (SD 2·2) to 19·7 nmol/L (9·2) and free testosterone concentrations increased from 222 pmol/L (62) to 364 pmol/L (222). In the placebo group, mean concentrations of serum total testosterone were 10·7

  11. Sexual desire in female-to-male transsexual persons: exploration of the role of testosterone administration.

    Science.gov (United States)

    Wierckx, Katrien; Elaut, Els; Van Caenegem, Eva; Van De Peer, Fleur; Dedecker, David; Van Houdenhove, Ellen; T'Sjoen, Guy

    2011-08-01

    To describe sexual desire in female-to-male transsexual persons post sex reassignment surgery (SRS). The associations between serum androgen levels and sexual desire are examined. Single center cross-sectional study. Forty-five female-to-male transsexual persons post SRS completed a standardized questionnaire assessing sexual desire (Sexual Desire Inventory). In addition, participants were asked questions on sexual desire before starting hormone treatment and having SRS. Serum levels of testosterone, LH and sex hormone-binding globulin were measured on fasting morning serum samples. In retrospect, 73.9% of the participants reported an increase in sexual desire after hormone treatment and SRS. Solitary sexual desire scores were significantly correlated with frequency of masturbation (r=0.835; Ptranssexual persons with elevated levels of LH, indicating suboptimal testosterone therapy, reported significantly lower solitary sexual desire levels (than those with low LH levels; P=0.007). Suppressed LH levels were also associated with having a higher need for sexual activities (P=0.009) and a higher frequency of excessive sexual desire (P=0.007). Most female-to-male transsexual persons report on a marked increase in sexual desire after testosterone treatment and SRS. No direct associations between levels of testosterone and solitary or dyadic sexual desire were found. However, measures of sexual desire were inversely associated with LH levels.

  12. Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder

    NARCIS (Netherlands)

    Enter, D.; Terburg, D.; Harrewijn, A.; Spinhoven, P.; Roelofs, K.

    2016-01-01

    Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially

  13. Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder

    NARCIS (Netherlands)

    Enter, Dorien; Terburg, David; Harrewijn, Anita; Spinhoven, Philip; Roelofs, Karin

    2015-01-01

    Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially

  14. Effects of testosterone administration on selective aspects of object-location memory in healthy young women

    NARCIS (Netherlands)

    Postma, A; Tuiten, A; van Honk, J; Kessels, RPC; Thijssen, J

    Previous work has indicated that object-location memory is sensitive to sex differences as well as variations in the menstrual cycle. The goal of the present study was to further examine the hormonal basis of human spatial memory by assessing the effects of a single dose of exogenous testosterone in

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

    Science.gov (United States)

    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 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 abusers compared with former AAS abusers and control participants (P 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 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 decreased AMH and inhibin B indicative of impaired spermatogenesis.

  16. Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.

    Science.gov (United States)

    Yu, Evan Y; Getzenberg, Robert H; Coss, Christopher C; Gittelman, Marc M; Keane, Thomas; Tutrone, Ronald; Belkoff, Laurence; Given, Robert; Bass, Joel; Chu, Franklin; Gambla, Michael; Gaylis, Franklin; Bailen, James; Hancock, Michael L; Smith, Jordan; Dalton, James T; Steiner, Mitchell S

    2015-02-01

    A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course. To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy. Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. GTx-758 and leuprolide. The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels. Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [pfree testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%). Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs. This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events. Clinicaltrials.gov identifier NCT01615120. Copyright

  17. Mumps Virus Decreases Testosterone Production and Gamma Interferon-Induced Protein 10 Secretion by Human Leydig Cells

    OpenAIRE

    Le Goffic, Ronan; Mouchel, Thomas; Ruffault, Annick; Patard, Jean-Jacques; Jégou, Bernard; Samson, Michel

    2003-01-01

    Mumps virus is responsible for sterility. Here, we show that the mumps virus infects Leydig cells in vitro and totally inhibits testosterone secretion and that ribavirin in mumps virus-infected Leydig cell cultures completely restores testosterone production. Moreover, we show that gamma interferon-induced protein 10 (IP-10) is highly expressed by mumps virus-infected Leydig cells and that ribavirin does not block IP-10 production.

  18. Decreased prevalence of left-handedness among females with male co-twins: evidence suggesting prenatal testosterone transfer in humans?

    Science.gov (United States)

    Vuoksimaa, Eero; Eriksson, C J Peter; Pulkkinen, Lea; Rose, Richard J; Kaprio, Jaakko

    2010-11-01

    Studies of singletons suggest that right-handed individuals may have higher levels of testosterone than do left-handed individuals. Prenatal testosterone levels are hypothesised to be especially related to handedness formation. In humans, female members from opposite-sex twin pairs may experience elevated level of prenatal exposure to testosterone in their intrauterine environment shared with a male. We tested for differences in rates of left-handedness/right-handedness in female twins from same-sex and opposite-sex twin pairs. Our sample consisted of 4736 subjects, about 70% of all Finnish twins born in 1983-1987, with information on measured pregnancy and birth related factors. Circulating testosterone and estradiol levels at age 14 were available on 771 and 744 of these twins, respectively. We found significantly (p=.006) lower prevalence of left-handedness in females from opposite-sex pairs (5.3%) compared to females from same-sex pairs (8.6%). The circulating levels of neither testosterone nor estradiol related to handedness in either females or males. Nor were there differences in circulating testosterone or estradiol levels between females from opposite-sex and same-sex twin pairs. Birth and pregnancy related factors for which we had information were unrelated to handedness. Our results are difficult to fully explain by postnatal factors, but they offer support to theory that relates testosterone to formation of handedness, and in a population-based sample, are suggestive of effects of prenatal testosterone transfer. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats.

    Science.gov (United States)

    Vlachou, Styliani; Guery, Sebastien; Froestl, Wolfgang; Banerjee, Deboshri; Benedict, Jessica; Finn, M G; Markou, Athina

    2011-05-01

    γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA(B) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA(B) receptor agonists, GABA(B) receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. We examined whether the acute effects of the GABA(B) receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self-administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. These results showed that BHF177 selectively blocked nicotine self-administration and prevented cue-induced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA(B) receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans.

  20. Finasteride, not tamsulosin, increases severity of erectile dysfunction and decreases testosterone levels in men with benign prostatic hyperplasia.

    Science.gov (United States)

    Traish, Abdulmaged M; Haider, Karim Sultan; Doros, Gheorghe; Haider, Ahmad

    2015-09-01

    5α-reductase inhibitors (5α-RIs) (finasteride and dutasteride) have been proven useful in treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). However, these inhibitors exert undesirable sexual side effects and, in some cases, these effects are persistent. There is considerable disagreement with regard to whether the adverse side effects resolve with continuous treatment. To investigate the long-term adverse effects of finasteride treatment in men with BPH on erectile function and to compare these adverse effects in men treated with the α1-adrenergic receptor blocker, tamsolusin. In this retrospective registry study, a cohort of 470 men aged between 47 and 68 years (mean 57.78±4.81) were treated with finasteride (5 mg/day). A second cohort of 230 men aged between 52 and 72 years (mean 62.62±4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 45 months. At intervals of 3 months and at each visit, plasma testosterone (T) levels and the international index of erectile function (IIEF-EF) questionnaire scores were determined. Long-term treatment with finasteride therapy is associated with worsening of erectile dysfunction (ED) as shown by the significant decrease in the IIEF-EF scores in men treated with finasteride. No worsening of ED was observed in men treated with tamsulosin. The increase in ED due to finasteride did not resolve with continued treatment with finasteride. Most importantly, long-term finasteride therapy resulted in reduction in total T levels, contributing to a state of hypogonadism. On the contrary, no changes in T levels were noted in men treated with tamsolusin. Our findings suggest that in men with BPH, long-term finasteride therapy but not tamsulosin results in worsening of ED and reduces total T concentrations. Clinicians are urged to discuss the impact of 5α-RIs therapy on sexual function with their patients before commencing this therapy.

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

    Directory of Open Access Journals (Sweden)

    Jon Jarløv Rasmussen

    Full Text Available 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 decreased AMH

  2. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

    DEFF Research Database (Denmark)

    Holm, Mette; Rajpert-De Meyts, Ewa; Andersson, Anna-Maria

    2003-01-01

    in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems...... were examined using a semi-quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin-B were correlated with the findings on histological examination......), and were rare in testes from controls (median = 0, p = 0.02). The proportion of testicular tissue occupied by Leydig cells increased with decreasing spermatogenic capacity. In contrast, the total volume of Leydig cells per testis was roughly comparable irrespective of the histological pattern...

  3. Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces.

    Science.gov (United States)

    Holtfrerich, Sarah K C; Schwarz, Katharina A; Sprenger, Christian; Reimers, Luise; Diekhof, Esther K

    2016-01-01

    Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.

  4. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

    DEFF Research Database (Denmark)

    Holm, Mette; Rajpert-De Meyts, Ewa; Andersson, Anna-Maria

    2003-01-01

    were examined using a semi-quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin-B were correlated with the findings on histological examination....... Leydig cell clusters of more than 15 cells in a cross-section, for which we proposed the name 'micronodules', were frequently seen in testicles exhibiting Sertoli-cell-only syndrome (SCO), a mixed pattern of impaired spermatogenesis, or complete spermatogenesis in combination with elevated FSH. Median...... in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems...

  5. Lipophagy Contributes to Testosterone Biosynthesis in Male Rat Leydig Cells.

    Science.gov (United States)

    Ma, Yi; Zhou, Yan; Zhu, Yin-Ci; Wang, Si-Qi; Ping, Ping; Chen, Xiang-Feng

    2018-02-01

    In recent years, autophagy was found to regulate lipid metabolism through a process termed lipophagy. Lipophagy modulates the degradation of cholesteryl esters to free cholesterol (FC), which is the substrate of testosterone biosynthesis. However, the role of lipophagy in testosterone production is unknown. To investigate this, primary rat Leydig cells and varicocele rat models were administered to inhibit or promote autophagy, and testosterone, lipid droplets (LDs), total cholesterol (TC), and FC were evaluated. The results demonstrated that inhibiting autophagy in primary rat Leydig cells reduced testosterone production. Further studies demonstrated that inhibiting autophagy increased the number and size of LDs and the level of TC, but decreased the level of FC. Furthermore, hypoxia promoted autophagy in Leydig cells. We found that short-term hypoxia stimulated testosterone secretion; however, the inhibition of autophagy abolished stimulated testosterone release. Hypoxia decreased the number and size of LDs in Leydig cells, but the changes could be largely rescued by blocking autophagy. In experimental varicocele rat models, the administration of autophagy inhibitors substantially reduced serum testosterone. These data demonstrate that autophagy contributes to testosterone biosynthesis at least partially through degrading intracellular LDs/TC. Our observations might reveal an autophagic regulatory mode regarding testosterone biosynthesis. Copyright © 2018 Endocrine Society.

  6. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, P

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...

  7. Oral administration of GZ-793A, a VMAT2 inhibitor, decreases methamphetamine self-administration in rats.

    Science.gov (United States)

    Wilmouth, Carrie E; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P; Bardo, Michael T

    2013-11-01

    Despite the high prevalence of use of methamphetamine (METH), there is no FDA-approved pharmacological treatment available currently for METH addiction. The vesicular monoamine transporter (VMAT2) has been proposed as a novel target to treat METH abuse. GZ-793A, a lobelane analog and selective VMAT2 inhibitor, has been shown previously to decrease METH self-administration specifically when administered via the subcutaneous route in rats. Since oral administration is the preferred clinical route, the present experiments determined if oral administration of GZ-793A would decrease specifically METH self-administration. Experiments 1 and 2 assessed the dose-effect functions of oral administration of GZ-793A (30-240 mg/kg) on intravenous METH self-administration and food-maintained responding, respectively. Experiments 3 and 4 assessed the time-course (20-180 min pretreatment) of oral administration of GZ-793A on METH self-administration and food-maintained responding, respectively. Oral administration of GZ-793A dose-dependently decreased METH self-administration, with the highest dose (240 mg/kg) producing an 85% decrease compared to control baseline. The decrease in METH self-administration produced by GZ-793A (120 mg/kg) lasted at least 180 min. In contrast, GZ-793A failed to alter food-maintained responding at any of the doses or pretreatment intervals tested. The oral effectiveness and the specificity of GZ-793A to decrease methamphetamine self-administration support the feasibility of developing VMAT2 inhibitors as treatments for METH abuse. © 2013.

  8. Cyp3a11-mediated testosterone-6β-hydroxylation decreased, while UGT1a9-mediated propofol O-glucuronidation increased, in mice with diabetes mellitus.

    Science.gov (United States)

    Shi, Rong; Wu, Jiasheng; Meng, Cong; Ma, Bingliang; Wang, Tianming; Li, Yuanyuan; Ma, Yueming

    2016-10-01

    The db/db mouse is one of the most popular animal models for type 2 diabetes mellitus, but changes in the activities of important P450s and UGTs are still not completely clear. This study was designed to investigate the alterations of major hepatic cytochrome P450s and UDP-glucuronyltransferase enzymes in db/db mice. Mouse liver microsomes (MLMs) were obtained from male db/db mice and their wild type littermates. After incubation of the substrates separately with MLMs, the samples were pooled and analysed by high-throughput liquid chromatography-tandem mass spectrometry system for the simultaneous study of nine phase I metabolic reactions and three glucuronidation conjugation reactions to determine the activity of the metabolic enzymes. Compared with normal controls, the Cl int estimate for testosterone-6β-hydroxylation was lower (46%) (p coumarin-7-hydroxylation, bupropion-hydroxylation, omeprazole-5-hydroxylation, dextromethorphan-O-demethylation, tolbutamide-4-hydroxylation, chlorzoxazone-6-hydroxylation and midazolam-1-hydroxylation and in glucuronidation reactions of estradiol 3-O-glucuronidation, and 3-azido-3-deoxythymidine glucuronidation. The data suggest that, in db/db mice, the activity of Cyp3a11, catalysing testosterone-6β-hydroxylation, decreased, while the activity of UGT1a9, catalysing propofol O-glucuronidation, increased. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Testosterone Topical

    Science.gov (United States)

    ... growth, development, and functioning of the male sexual organs and typical male characteristics. Testosterone topical works by ... clean and completely dry. Open your testosterone topical container. If you are using a packet, fold the ...

  10. Exogenous testosterone, finasteride and castration effects on testosterone, insulin, zinc and chromium in adult male rats.

    Science.gov (United States)

    Yousofvand, Namdar; Zarei, Fatemeh; Ghanbari, Ali

    2013-01-01

    Although effects of trace elements on secretion of sex steroids and insulin have been studied, the effects of these hormones on serum level of trace elements have been rarely investigated. The aim of the present study was to evaluate the effect of testosterone and finasteride administration and castration on serum levels of testosterone, insulin, zinc and chromium. Male adult rats (n = 32) were divided into 4 groups (n = 8). Group 1, control; Group 2, castration, castration was done at the first day of the study; Group 3, finasteride (20 mg/kg/day, dissolved in drinking water) and Group 4, testosterone (5 mg/kg/day, i.p.). At the end of the period of the study (35 days), serum testosterone, insulin, zinc and chromium levels were determined in the blood samples collected directly from the right atrium of the heart of the animals. The data indicated that the serum levels of testosterone, insulin and zinc were significantly increased (Pfinasteride groups, but the level of chromium was decreased in both groups (Pfinasteride increases insulin and zinc levels and decreases chromium levels in the serum of male adult rats. According to these data, it seems that testosterone may affect glucose cycle through effect on serum insulin levels and trace elements such as zinc and chromium.

  11. Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: a review of trial data.

    Science.gov (United States)

    Carson, Culley C; Rosano, Giuseppe

    2012-01-01

    Increasing interest in the use of supplemental testosterone has led to a heightened focus on the safety of testosterone in elderly males, with a particular emphasis on cardiovascular risk. To evaluate, based on available clinical trial data, whether exogenous testosterone administration in middle-aged to elderly men increases cardiovascular risk, and to assess whether these effects differ in hypogonadal vs. eugonadal subjects. MEDLINE search from 2004 to present of all meta-analyses and randomized, controlled clinical trials of testosterone administration in male subjects ≥ 45 years old that included measurements of cardiovascular outcomes or known cardiovascular risk factors before and after treatment with testosterone. The effects of testosterone treatment on cardiovascular events and cardiovascular risk factors were assessed. In clinical trials where testosterone has been used in patients with preexisting cardiovascular conditions, the effect on disease symptoms has typically been either neutral or beneficial. Based on clinical trial data, testosterone treatment has minimal effect on cardiovascular risk factors with the exception of an increase in hematocrit, which is consistently seen with testosterone treatment, and a decrease in high-density lipoprotein cholesterol, which is an inconsistent response. Responses of hypogonadal and eugonadal men to testosterone treatment in terms of cardiovascular risk are generally similar. Testosterone treatment has not been reported to increase the incidence of cardiovascular events with the possible exception of one trial in frail elderly men. Available clinical trial data indicate that the use of testosterone in middle-aged to elderly men does not increase cardiovascular risk nor does it unfavorably modify cardiovascular risk profile. Prospective data from large, well-designed, long-term trials of testosterone treatment are lacking and will be required to verify the cardiovascular efficacy/safety of chronic treatment.

  12. Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome.

    Science.gov (United States)

    Vosnakis, Christos; Georgopoulos, Neoklis A; Armeni, Anastasia K; Papadakis, Efstathios; Roupas, Nikolaos D; Katsikis, Ilias; Panidis, Dimitrios

    2012-08-01

    To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment. Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment. A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. The Effects of Testosterone on Oxidative Stress Markers in Mice with Spinal Cord Injuries

    Directory of Open Access Journals (Sweden)

    Hamid Choobineh

    2016-05-01

    Full Text Available Background: Spinal cord injury (SCI causes infertility in male patients through erectile dysfunction, ejaculatory dysfunction, semen and hormone abnormalities. Oxidative stress (OS is involved in poor semen quality and subsequent infertility in males with SCI. The aim of this study is to examine the effects of SCI on the level of testosterone hormone. Materials and Methods: In this experimental study, we evaluated the effects of exogenous testosterone on the activity of the antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GPx as well as the levels of malondialdehyde (MDA and protein carbonylation (PCO, as markers of OS, in 10 groups of SCI mice. Total antioxidant capacity (TAC was determined using the 2,29-azinobis-(3-ethylbenzothiazoline- 6-sulfonic acid (ABTS radical cation assay. Results: Exogenous testosterone administration in mice with SCI significantly reduced SOD and GPx enzyme activities and MDA level. There was no significant decrease in PCO content. In addition, TAC remarkably increased in the sham and SCI groups not treated with testosterone but remained unchanged in all other experimental groups. Exogenous testosterone also reduced serum testosterone levels in all groups except the positive control group. Conclusion: Our cumulative data indicated that SCI could cause sterility by disturbing the plasmatic testosterone balance. The normal level of endogenous testosterone was not completely restored by exogenous testosterone administration.

  14. Effect of pineal gland on testosterone release in vitro.

    Science.gov (United States)

    Jarrige, J F; Thieblot, P; Boucher, D

    1986-01-01

    We studied the effect of hCG, aminoglutethimide and pineal effluent on the basal testosterone secretion by superfused adult rat interstitial cells. The period used to determine the mean rates of release was 120-240 min. after the start of superfusion i.e. when basal secretory rate was stable. A 2 h administration of hCG (10 mUI/ml) induced a rapid increase in testosterone output while aminoglutethimide (100 microM) decreased it. Basal testosterone release was not modified when interstitial cells were superfused with effluent of a chamber containing 1, 2 or 4 pineal glands. These results suggest that pineal secretory products exert no direct acute action on testosterone biosynthesis by rat interstitial cells.

  15. The many faces of testosterone

    Directory of Open Access Journals (Sweden)

    Jerald Bain

    2008-01-01

    Full Text Available Jerald BainDepartment of Medicine, Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario, CanadaAbstract: Testosterone is more than a “male sex hormone”. It is an important contributor to the robust metabolic functioning of multiple bodily systems. The abuse of anabolic steroids by athletes over the years has been one of the major detractors from the investigation and treatment of clinical states that could be caused by or related to male hypogonadism. The unwarranted fear that testosterone therapy would induce prostate cancer has also deterred physicians form pursuing more aggressively the possibility of hypogonadism in symptomatic male patients. In addition to these two mythologies, many physicians believe that testosterone is bad for the male heart. The classical anabolic agents, 17-alkylated steroids, are, indeed, potentially harmful to the liver, to insulin action to lipid metabolism. These substances, however, are not testosterone, which has none of these adverse effects. The current evidence, in fact, strongly suggests that testosterone may be cardioprotective. There is virtually no evidence to implicate testosterone as a cause of prostate cancer. It may exacerbate an existing prostate cancer, although the evidence is flimsy, but it does not likely cause the cancer in the first place. Testosterone has stimulatory effects on bones, muscles, erythropoietin, libido, mood and cognition centres in the brain, penile erection. It is reduced in metabolic syndrome and diabetes and therapy with testosterone in these conditions may provide amelioration by lowering LDL cholesterol, blood sugar, glycated hemoglobin and insulin resistance. The best measure is bio-available testosterone which is the fraction of testosterone not bound to sex hormone binding globulin. Several forms of testosterone administration are available making compliance

  16. Administration of noradrenaline in the autonomic ganglia modifies the testosterone release from the testis using an ex vivo system.

    Science.gov (United States)

    Sosa, Zulema Y; Palmada, Miguel N; Fóscolo, Mabel R; Capani, Francisco; Conill, Alberto; Cavicchia, Juan Carlos

    2009-08-01

    The male gonad receives nerve fibres from the autonomic ganglionic system. These fibres converge on the testis along two pathways, the superior and the inferior spermatic nerves. The superior spermatic nerve runs from the superior mesenteric ganglion alongside the testicular artery, whereas the inferior spermatic nerve originates in inferior mesenteric ganglion, accompanies the vas deferens and penetrates the inferior pole of the testis. The aim of this work was to evaluate androgen release after the addition of noradrenaline or adrenoreceptor antagonists (propranolol or phentolamine) to the ganglionic compartment. An ex vivo system used in a previous work was incubated in two separate containers, one for the testis and the other for the ganglion. Both organs remain interconnected (as in vivo) by the respective spermatic nerve. When noradrenaline was added to the inferior mesenteric ganglion, testosterone release in the gonad container underwent a progressive and significant increment. Propranolol diminishes and phentolamine increases the androgen release. When using the superior mesenteric ganglion, no changes were observed. These results indicate that the ganglionic stimulation of the autonomic system clearly participates in testosterone release from the testis. This effect depends on the ganglion involved. These results make it evident that not only the classical and well-known hypothalamus-hypophysial axis, but also the peripheral nervous system, via the autonomic ganglia, are directly involved in the endocrine control of the testis.

  17. Testosterone Induces Erythrocytosis via Increased Erythropoietin and Suppressed Hepcidin: Evidence for a New Erythropoietin/Hemoglobin Set Point

    Science.gov (United States)

    Travison, Thomas G.; Basaria, Shehzad; Davda, Maithili N.; Guo, Wen; Li, Michelle; Connor Westfall, John; Bae, Harold; Gordeuk, Victor; Bhasin, Shalender

    2014-01-01

    Background. The mechanisms by which testosterone increases hemoglobin and hematocrit remain unclear. Methods. We assessed the hormonal and hematologic responses to testosterone administration in a clinical trial in which older men with mobility limitation were randomized to either placebo or testosterone gel daily for 6 months. Results. The 7%–10% increase in hemoglobin and hematocrit, respectively, with testosterone administration was associated with significantly increased erythropoietin (EPO) levels and decreased ferritin and hepcidin levels at 1 and 3 months. At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point. Consistent with increased iron utilization, soluble transferrin receptor (sTR) levels and ratio of sTR/log ferritin increased significantly in testosterone-treated men. Hormonal and hematologic responses were similar in anemic participants. The majority of testosterone-treated anemic participants increased their hemoglobin into normal range. Conclusions. Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations. We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis. PMID:24158761

  18. Acute bouts of wheel running decrease cocaine self-administration: Influence of exercise output.

    Science.gov (United States)

    Smith, Mark A; Fronk, Gaylen E; Zhang, Huailin; Magee, Charlotte P; Robinson, Andrea M

    Exercise is associated with lower rates of drug use in human populations and decreases drug self-administration in laboratory animals. Most of the existing literature examining the link between exercise and drug use has focused on chronic, long-term exercise, and very few studies have examined the link between exercise output (i.e., amount of exercise) and drug self-administration. The purpose of this study was to examine the effects of acute bouts of exercise on cocaine self-administration, and to determine whether these effects were dependent on exercise output and the time interval between exercise and drug self-administration. Female rats were trained to run in automated running wheels, implanted with intravenous catheters, and allowed to self-administer cocaine on a fixed ratio (FR1) schedule of reinforcement. Immediately prior to each test session, subjects engaged in acute bouts of exercise in which they ran for 0, 30, or 60min at 12m/min. Acute bouts of exercise before test sessions decreased cocaine self-administration in an output-dependent manner, with the greatest reduction in cocaine intake observed in the 60-min exercise condition. Exercise did not reduce cocaine self-administration when wheel running and test sessions were separated by 12h, and exercise did not reduce responding maintained by food or responding during a saline substitution test. These data indicate that acute bouts of exercise decrease cocaine self-administration in a time- and output-dependent manner. These results also add to a growing body of literature suggesting that physical activity may be an effective component of drug abuse treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training.

    Science.gov (United States)

    Liu, Te-Chih; Lin, Che-Hung; Huang, Chih-Yang; Ivy, John L; Kuo, Chia-Hua

    2013-07-01

    With advancing age, plasma testosterone levels decline, with free testosterone levels declining more significantly than total testosterone. This fall is thought to underlie the development of physical and mental weakness that occurs with advancing age. In addition, vigorous exercise can also lower total and free testosterone levels with the decline greatest in physically untrained men. The purpose of the study was to evaluate the effect of oral DHEA supplementation, a testosterone precursor, on free testosterone in sedentary middle-aged men during recovery from a high-intensity interval training (HIIT) bout of exercise. A randomized, double-blind, placebo-controlled crossover study was conducted for 8 middle-aged participants (aged 49.3 ± 2.4 years) and an additional 8 young control participants (aged 21.4 ± 0.3 years). Each participant received DHEA (50 mg) and placebo on separate occasions one night (12 h) before a 5-session, 2-min cycling exercise (100% VO₂max). While no significant age difference in total testosterone was found, middle-aged participants exhibited significantly lower free testosterone and greater luteinizing hormone (LH) levels than the young control group. Oral DHEA supplementation increased circulating DHEA-S and free testosterone levels well above baseline in the middle-aged group, with no significant effect on total testosterone levels. Total testosterone and DHEA-S dropped significantly until 24 h after HIIT for both age groups, while free testosterone of DHEA-supplemented middle-aged men remained unaffected. These results demonstrate acute oral DHEA supplementation can elevate free testosterone levels in middle-aged men and prevent it from declining during HIIT. Therefore, DHEA supplementation may have significant benefits related to HIIT adaptation.

  20. A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire.

    Science.gov (United States)

    Burger, Henry G; Papalia, Mary-Anne

    2006-05-01

    The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen-replete and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognise that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development.

  1. Repeated Administration of the GABA\\(_B\\) Receptor Positive Modulator BHF177 Decreased Nicotine Self-Administration, and Acute Administration Decreased Cue-Induced Reinstatement of Nicotine Seeking in Rats

    OpenAIRE

    Vlachou, Styliani; Guery, Sebastien; Froestl, Wolfgang; Benedict, Jessica; Finn, M. G.; Markou, Athina; Banerjee, Deboshri

    2011-01-01

    Abstract: Rationale \\(\\gamma\\)-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA\\(_B\\) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA\\(_B\\) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with...

  2. Testosterone and weight loss: the evidence

    Science.gov (United States)

    Traish, Abdulmaged M.

    2014-01-01

    Purpose of review The purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency. Recent findings Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome. The aforementioned improvements are attributed to improved mitochondrial function, increased energy utilization, increased motivation and vigor resulting in improved cardio-metabolic function and enhanced physical activity. Summary The implication of testosterone therapy in management of obesity in men with testosterone deficiency is of paramount clinical significance, as it produces sustained weight loss without recidivism. On the contrary, alternative therapeutic approaches other than bariatric surgery failed to produce significant and sustained outcome and exhibit a high rate of recidivism. These findings represent strong foundations for testosterone therapy in obese men with testosterone deficiency and should spur clinical research for better understanding of usefulness of testosterone therapy in treatment of underlying pathophysiological conditions of obesity. PMID:25105998

  3. Effect of exogenous testosterone, finasteride, and castration on serum level of thyroxin.

    Science.gov (United States)

    Zarei, Fatemeh; Yousofvand, Namdar; Khazaei, Mozafar; Ghanbari, Ali

    2013-01-01

    The secretion of thyroxin (T4) as the main hormone of thyroid gland is regulated by androgens. The present study aimed to evaluate the effect of testosterone and finasteride administration and castration on serum levels of T4 and to show the effect of this regulation on total body weight, weight of testis, and the weight of prostate. Male adult rats (n = 32) were divided into 4 groups (n = 8): Group 1 (control), Group 2 (castration), Group 3 (finasteride: 20 mg/kg/day) and Group 4 (testosterone: 5 mg/kg/day). At the end of the study (35 days), serum level of thyroxin, body weight, weight of testis, and prostate were determined. The data showed that the body weight increased in castrated (P = 0.04) and decreased in testosterone (P = 0.00) groups but did not differ in finasteride (P>0.05) group. There were not any differences in the weight of testis among control, finasteride, and testosterone groups but the weight of prostate increased in testosterone group (P = 0.00) and decreased in castrated (P = 0.03) and finasteride groups (P = 0.04). In addition, the serum level of T4 (nmo/ml) decreased in the three groups: finasteride (P = 0.03), testosterone (P = 0.04), and castrated (P = 0.00). Testosterone in both high and low levels decreased the amount of T4 with a time-dependent manner.

  4. Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies.

    Science.gov (United States)

    Speisky, H; MacDonald, A; Giles, G; Orrego, H; Israel, Y

    1985-01-01

    The effect of acute ethanol administration on rates of synthesis and utilization of hepatic glutathione (GSH) was studied in rats after a pulse of [35S]cysteine. A 35% decrease in hepatic GSH content 5h after administration of 4 g of ethanol/kg body wt. was accompanied by a 33% increase in the rate of GSH utilization. The decrease occurred without increases in hepatic oxidized glutathione (GSSG) or in the GSH/GSSG ratio. The rate of non-enzymic condensation of GSH with acetaldehyde could account for only 6% of the rate of hepatic GSH disappearance. The increased loss of [35S]GSH induced by ethanol was not accompanied by an increased turnover; rather, a 30% inhibition of GSH synthesis balanced the increased rate of loss, leaving the turnover rate unchanged. The rate of acetaldehyde condensation with cysteine in vitro occurred at about one-third of the rate of GSH loss in ethanol-treated animals. However, ethanol induced only a minor decrease in liver cysteine content, which did not precede, but followed, the decrease in GSH. The characteristics of 2-methylthiazolidine-4-carboxylic acid, the condensation product between acetaldehyde and cysteine, were studied and methodologies were developed to determine its presence in tissues. It was not found in the liver of ethanol-treated animals. Ethanol administration led to a marked increase (47%) in plasma GSH in the post-hepatic inferior vena cava, but not in its pre-hepatic segment. Data suggest that an increased loss of GSH from the liver constitutes an important mechanism for the decrease in GSH induced by ethanol. In addition, an inhibition of GSH synthesis is observed. PMID:3977847

  5. Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

    Science.gov (United States)

    Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

    2011-01-01

    Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

  6. Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V.

    Science.gov (United States)

    Fernandez, T; Torres, M J; R-Pena, R; Fuentes, M S; Robles, S; Mayorga, C; Blanca, M

    2005-12-01

    Subjects with IgE responses to betalactams can develop selective or cross-reactive responses after the administration of penicillin derivatives. After the reaction, however, the hapten induces a boosting phenomenon, which may increase the titre and the affinity of the antibody, with the resulting risk of developing allergic reactions to other penicillins. To determine in subjects with selective responses to amoxicillin (AX) and good tolerance to benzylpenicillin (BP) and penicillin V (PV) whether the administration of these compounds induced any change in specificity, measured by either skin or in vitro testing, which could predict the appearance of cross-reactivity. Ten subjects with a selective response to AX were followed-up for 2 years with the periodic administration of penicillin G and V (Group A) and compared with another group composed of 10 persons with identical clinical characteristics but without repeated penicillin administration (Group B). Periodic in vitro and in vivo measurements of specific IgE antibodies were performed at 6-month intervals. Patients were randomized to Group A or B according to their order of inclusion. In both groups, skin test reactivity tended to decrease, and although greater in Group A, the difference was not significant compared with Group B. Median RAST values also decreased over time and showed no differences in the exposed group compared with the controls. One patient in Group A became positive to benzylpenicilloyl (BPO), despite becoming negative to AX. Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

  7. Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces.

    Directory of Open Access Journals (Sweden)

    Sarah K C Holtfrerich

    Full Text Available Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.

  8. Repeated phencyclidine administration alters glutamate release and decreases GABA markers in the prefrontal cortex of rats

    Science.gov (United States)

    Amitai, Nurith; Kuczenski, Ronald; Behrens, M. Margarita; Markou, Athina

    2011-01-01

    Repeated phencyclidine (PCP) administration induces cognitive disruptions resembling those seen in schizophrenia. Alterations in glutamate transmission and γ-aminobutyric acid (GABA) function in the prefrontal cortex (PFC) have been implicated in these PCP-induced deficits, as well as in cognitive symptoms of schizophrenia. PCP-induced cognitive deficits are reversed by chronic treatment with the atypical antipsychotic clozapine in rats. We investigated the effects of a single injection vs. repeated administration of PCP on glutamate levels in the PFC using in vivo microdialysis. Furthermore, we examined how these PCP regimens affect GABA neuronal markers in the PFC. Finally, we investigated the effects of clozapine on disruptions in glutamate levels and GABA neuronal markers induced by repeated PCP administration. Acute PCP administration (2 mg/kg) increased extracellular PFC glutamate; this increase appeared blunted, but was not eliminated, after repeated PCP pretreatment. PCP administration also strongly decreased levels of parvalbumin and glutamic acid decarboxylase-67 (two markers of GABA function) in the PFC, an effect that was maintained after a 10 day drug-free washout period and unaltered by the resumption of repeated PCP injections. All of the observed PCP effects were attenuated by chronic treatment with clozapine, an atypical antipsychotic that has partial effectiveness on cognitive impairment in schizophrenia. These findings suggest that abnormal cortical glutamate transmission, possibly driven by pathological changes in GABA function in parvalbumin-positive fast-spiking interneurons, may underlie some of the cognitive deficits in schizophrenia. A better understanding of glutamate and GABA dysregulation in schizophrenia may uncover new treatment targets for schizophrenia-related cognitive dysfunction. PMID:21238466

  9. Decreases in colonic and systemic inflammation in chronic HIV infection after IL-7 administration.

    Directory of Open Access Journals (Sweden)

    Irini Sereti

    2014-01-01

    Full Text Available Despite antiretroviral therapy (ART, some HIV-infected persons maintain lower than normal CD4(+ T-cell counts in peripheral blood and in the gut mucosa. This incomplete immune restoration is associated with higher levels of immune activation manifested by high systemic levels of biomarkers, including sCD14 and D-dimer, that are independent predictors of morbidity and mortality in HIV infection. In this 12-week, single-arm, open-label study, we tested the efficacy of IL-7 adjunctive therapy on T-cell reconstitution in peripheral blood and gut mucosa in 23 ART suppressed HIV-infected patients with incomplete CD4(+ T-cell recovery, using one cycle (consisting of three subcutaneous injections of recombinant human IL-7 (r-hIL-7 at 20 µg/kg. IL-7 administration led to increases of both CD4(+ and CD8(+ T-cells in peripheral blood, and importantly an expansion of T-cells expressing the gut homing integrin α4β7. Participants who underwent rectosigmoid biopsies at study baseline and after treatment had T-cell increases in the gut mucosa measured by both flow cytometry and immunohistochemistry. IL-7 therapy also resulted in apparent improvement in gut barrier integrity as measured by decreased neutrophil infiltration in the rectosigmoid lamina propria 12 weeks after IL-7 administration. This was also accompanied by decreased TNF and increased FOXP3 expression in the lamina propria. Plasma levels of sCD14 and D-dimer, indicative of systemic inflammation, decreased after r-hIL-7. Increases of colonic mucosal T-cells correlated strongly with the decreased systemic levels of sCD14, the LPS coreceptor - a marker of monocyte activation. Furthermore, the proportion of inflammatory monocytes expressing CCR2 was decreased, as was the basal IL-1β production of peripheral blood monocytes. These data suggest that administration of r-hIL-7 improves the gut mucosal abnormalities of chronic HIV infection and attenuates the systemic inflammatory and coagulation

  10. Intraperitoneal Bilirubin Administration Decreases Infarct Area in a Rat Coronary Ischemia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Ron eBen-Amotz

    2014-02-01

    Full Text Available Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 hour before injury would decrease infarct area and preserve left ventricular (LV systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-hour period of reperfusion. LV function was estimated by measurements of fractional shortening and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats fractional shortening was less depressed during the period of ischemia (18.8 vs 25.8%, p = 0.034. Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34% vs 25.5%, p = 0.0067. Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

  11. Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy.

    Science.gov (United States)

    Birzniece, Vita; Umpleby, Margot A; Poljak, Anne; Handelsman, David J; Ho, Ken K Y

    2013-09-01

    In hypopituitary men, oral delivery of unesterified testosterone in doses that result in a solely hepatic androgen effect enhances protein anabolism during GH treatment. In this study, we aimed to determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women. Eight healthy postmenopausal women received 2-week treatment with oral testosterone at a dose of 40 mg/day (crystalline testosterone USP). This dose increases portal concentrations of testosterone, exerting androgenic effects on the liver without a spillover into the systemic circulation. The outcome measures were whole-body leucine turnover, from which leucine rate of appearance (LRa, an index of protein breakdown) and leucine oxidation (Lox, a measure of irreversible protein loss) were estimated, energy expenditure and substrate utilization. We measured the concentration of liver transaminases as well as of testosterone, SHBG and IGF1. Testosterone treatment significantly reduced LRa by 7.1 ± 2.5% and Lox by 14.6 ± 4.5% (Panabolism by reducing protein breakdown and oxidation without inducing systemic androgen excess in women. We conclude that a small oral dose of unesterified testosterone holds promise as a simple novel treatment of protein catabolism and muscle wasting.

  12. Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

    Science.gov (United States)

    Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

    2015-01-01

    Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4–6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects (‘good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1–51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of ‘good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder. PMID:25881117

  13. Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

    Science.gov (United States)

    Rando, Jessica; Broering, Derek; Olson, James E; Marco, Catherine; Evans, Stephen B

    2015-09-01

    This study sought to answer the question, "Can police officers administer intranasal naloxone to drug overdose victims to decrease the opioid overdose death rate?" This prospective interventional study was conducted in Lorain County, OH, from January 2011 to October 2014. Starting October 2013, trained police officers administered naloxone to suspected opioid overdose victims through a police officer naloxone prescription program (NPP). Those found by the county coroner to be positive for opioids at the time of death and those who received naloxone from police officers were included in this study. The rate of change in the total number of opioid-related deaths in Lorain County per quarter year, before and after initiation of the NPP, and the trend in the survival rate of overdose victims who were given naloxone were analyzed by linear regression. Significance was established a priori at P overdose deaths increased significantly before initiation of the police officer NPP with average deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the first 9 months of 2013. After initiation of the police officer NPP, the number of opioid overdose deaths decreased each quarter with an overall average of 13.4. Of the 67 participants who received naloxone by police officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up. Intranasal naloxone administration by police first responders is associated with decreased deaths in opioid overdose victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... on reproductive outcome. The rationale for asking this question lies in the existing scientific evidence derived from basic research and animal studies regarding the action of androgens during folliculogenesis, showing that their main effect in follicular development is defined during the earlier developmental...

  15. Lactobacillus casei CRL 431 administration decreases inflammatory cytokines in a diet-induced obese mouse model.

    Science.gov (United States)

    Novotny Núñez, Ivanna; Maldonado Galdeano, Carolina; de Moreno de LeBlanc, Alejandra; Perdigón, Gabriela

    2015-01-01

    Obesity is a chronic disease associated with an inflammatory process in which cytokines play an important role. Probiotic microorganisms have been associated with modulation of the host immune system. The aim of this study was to evaluate the influence of the probiotic bacterium Lactobacillus casei CRL 431 on the cytokine response in a model of mice under high-fat diet (HFD) conditions. BALB/c mice received a conventional balanced diet or an HFD. The test groups received milk, milk fermented by L. casei (FM), or L. casei as suspension in the drinking water. Proinflammatory and regulatory cytokine producer cells were evaluated in the small intestine and liver; the cytokine levels in the intestinal fluids were also evaluated. The percentages of immune cells as macrophages (F4/80), NKT, CD4+, CD8+ populations were determined in the liver. Adipocytes were also isolated and cultured to evaluate cytokines and the chemokine monocyte chemoattractant protein (MCP)-1 produced by them. The administration of probiotic L. casei CRL 431 exerted an anti-inflammatory response in mice fed an HFD, evidenced mainly by decreasing proinflammatory cytokines, such as interleukin (IL)-6, IL-17, and tumor necrosis factor-α. Probiotic administration also was associated with fewer immune-infiltrating cells in the liver of mice that received the HFD and decreased secretion of MCP-1 by the adipocytes. This last observation could be associated with less macrophage accumulation in the adipose tissues, which is characteristic in the obese host and contributes to maintaining the inflammatory response in this organ. The results obtained show an anti-inflammatory effect of L. casei CRL 431 when it is administered as a supplement of the HFD in a mouse model. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Pharmacokinetics of testosterone cream applied to scrotal skin.

    Science.gov (United States)

    Iyer, R; Mok, S F; Savkovic, S; Turner, L; Fraser, G; Desai, R; Jayadev, V; Conway, A J; Handelsman, D J

    2017-07-01

    Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route. © 2017 American Society of Andrology and European Academy of Andrology.

  17. Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats.

    Science.gov (United States)

    Kahler, A; Geary, N; Eckel, L A; Campfield, L A; Smith, F J; Langhans, W

    1998-07-01

    The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3 through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g (or 13-20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.

  18. Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone.

    Science.gov (United States)

    Dias, Jenny Pena; Veldhuis, Johannes D; Carlson, Olga; Shardell, Michelle; Chia, Chee W; Melvin, Denise; Egan, Josephine M; Basaria, Shehzad

    2017-04-01

    Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone. Thirty-seven men, ≥65years with total testosterone testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months. At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059). In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased...

  20. Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated rats

    Directory of Open Access Journals (Sweden)

    Rui Li

    2016-05-01

    Full Text Available Testosterone is overwhelmingly important in regulating erectile physiology. However, the associated molecular mechanisms are poorly understood. The purpose of this study was to explore the effects and mechanisms of testosterone in erectile dysfunction (ED in castrated rats. Forty male Sprague-Dawley rats were randomized to four groups (control, sham-operated, castration and castration-with-testosterone-replacement. Reactive oxygen species (ROS production was measured by dihydroethidium (DHE staining. Erectile function was assessed by the recording of intracavernous pressure (ICP and mean arterial blood pressure (MAP. Protein expression levels were examined by western blotting. We found that castration reduced erectile function and that testosterone restored it. Nitric oxide synthase (NOS activity was decrease in the castrated rats, and testosterone administration attenuated this decrease (each p < 0.05. The testosterone, dihydrotestosterone, cyclic guanosine monophosphate (cGMP and cyclic adenosine monophosphate (cAMP concentrations were lower in the castrated rats, and testosterone restored these levels (each p < 0.05. Furthermore, the cyclooxygenase-2 (COX-2 and prostacyclin synthase (PTGIS expression levels and phospho-endothelial nitric oxide synthase (p-eNOS, Ser1177/endothelial nitric oxide synthase (eNOS ratio were reduced in the castrated rats compared with the controls (each p < 0.05. In addition, the p40phox and p67phox expression levels were increased in the castrated rats, and testosterone reversed these changes (each p < 0.05. Overall, our results demonstrate that testosterone ameliorates ED after castration by reducing ROS production and increasing the activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

  1. Effect of testosterone on oxidative stress and cell damage induced by 3-nitropropionic acid in striatum of ovariectomized rats.

    Science.gov (United States)

    Túnez, Isaac; Feijóo, Montserrat; Collado, Juan A; Medina, Francisco J; Peña, José; Muñoz, María del C; Jimena, Ignacio; Franco, Francisco; Rueda, Ignacio; Muntané, Jordi; Montilla, Pedro

    2007-03-06

    This paper evaluates the effects of testosterone (0.5 mg/kg subcutaneously (s.c.) for 8 days) on oxidative stress and cell damage induced by 3-nitropropionic acid (20 mg/kg intraperitoneally (i.p.) for 4 days) in ovariectomized rats. Gonadectomy triggered oxidative damage and cell loss, evaluated by the detection of caspase-3, whereas 3-nitropropionic acid increased the levels of oxidative stress induced by ovariectomy and prompted cell damage characterized by enhanced levels of lactate dehydrogenase. These changes were blocked by testosterone administration. Our results support the following conclusions: i) ovariectomy triggers oxidative and cell damage via caspase-3 in the striatum; ii) 3-nitropropionic acid exacerbates oxidative stress induced by ovariectomy and leads to cell damage characterized by increased levels of lactate dehydrogenase; iii) testosterone administration decreases oxidative stress and cell damage. Additionally, these data support the hypothesis that testosterone might play an important role in the onset and development of neurodegenerative diseases.

  2. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive : II. Clinical effects

    NARCIS (Netherlands)

    Zimmerman, Y.; Foidart, J. M.; Pintiaux, A.; Minon, J. M.; Fauser, B. C J M; Cobey, K.; Coelingh Bennink, H. J T

    2015-01-01

    Objectives Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that 'co-administration' of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP)-containing COC

  3. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive : I. Endocrine effects

    NARCIS (Netherlands)

    Zimmerman, Y.; Foidart, J. M.; Pintiaux, A.; Minon, J. M.; Fauser, B. C J M; Cobey, K.; Coelingh Bennink, H. J T

    2015-01-01

    Objectives Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). Study design In this randomized, double-blind, placebo-controlled study

  4. [Testosterone therapy improves cardiac function of male rats with right heart failure].

    Science.gov (United States)

    Li, Zong-Bin; Wang, Jing; Wang, Ju-Xiang; Chen, Xun-Min; Jiang, Shi-Sen

    2009-11-01

    Clinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats. Forty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations. The level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups. Physiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.

  5. Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.

    Science.gov (United States)

    Kato, Karin; Nagao, Miki; Yamamoto, Masaki; Matsumura, Yasufumi; Takakura, Shunji; Fukuda, Kazuhiko; Ichiyama, Satoshi

    2016-01-01

    Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole. Copyright © 2015. Published by Elsevier Ltd.

  6. Testosterone treatment of hypogonadal men participating in competitive sports.

    Science.gov (United States)

    Gooren, L J; Behre, H M

    2008-06-01

    Testosterone has a steeply dose-dependent effect on muscle mass and strength irrespective of gonadal status. So, for reasons of fairness, people who engage in competitive sports should not administer exogenous testosterone raising their blood testosterone levels beyond the range of normal. There is a ban on exogenous androgens for men and women in sports, but an exception has been made for men with androgen deficiency due to pituitary or testicular disease. Men who receive testosterone administration for the indication hypogonadism have an interest in the use of testosterone preparations generating blood testosterone levels within the normal range of healthy, eugonadal men. On the grounds of a positive correlation between blood testosterone concentrations muscle and volume/strength, they are best served with a parenteral testosterone preparation, rather than transdermal testosterone, but they should not run the risk of being excluded from competition because of supraphysiological testosterone levels. The latter is a realistic risk with the traditional parenteral testosterone esters. The new parenteral testosterone undecanoate preparation offers much better perspectives. Its pharmacokinetics have been investigated in detail and there is a fair degree of predictability of resulting blood testosterone levels with use of this preparation.

  7. Testosterone Reduces Knee Passive Range of Motion and Expression of Relaxin Receptor Isoforms via 5α-Dihydrotestosterone and Androgen Receptor Binding

    Directory of Open Access Journals (Sweden)

    Firouzeh Dehghan

    2014-03-01

    Full Text Available Ovarian steroids such as estrogen and progesterone have been reported to influence knee laxity. The effect of testosterone, however, remains unknown. This study investigated the effect of testosterone on the knee range of motion (ROM and the molecular mechanisms that might involve changes in the expression of relaxin receptor isoforms, Rxfp1 and Rxfp2 in the patella tendon and lateral collateral ligament of the female rat knee. Ovariectomized adult female Wistar rats received three days treatment with peanut oil (control, testosterone (125 and 250 μg/kg and testosterone (125 and 250 μg/kg plus flutamide, an androgen receptor blocker or finasteride, a 5α-reductase inhibitor. Duplicate groups received similar treatment however in the presence of relaxin (25 ng/kg. A day after the last drug injection, knee passive ROM was measured by using a digital miniature goniometer. Both tendon and ligament were harvested and then analysed for protein and mRNA expression for Rxfp1 and Rxfp2 respectively. Knee passive ROM, Rxfp1 and Rxfp2 expression were significantly reduced following treatment with testosterone. Flutamide or finasteride administration antagonized the testosterone effect. Concomitant administration of testosterone and relaxin did not result in a significant change in knee ROM as compared to testosterone only treatment; however this was significantly increased following flutamide or finasteride addition. Testosterone effect on knee passive ROM is likely mediated via dihydro-testosterone (DHT, and involves downregulation of Rxfp1 and Rxfp2 expression, which may provide the mechanism underlying testosterone-induced decrease in female knee laxity.

  8. Comparison of methods for determination of testosterone and non-protein bound testosterone in men with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick

    1986-01-01

    The serum concentrations of testosterone and of non-protein bound testosterone were determined in 28 men with alcoholic liver disease having normal to decreased serum albumin concentrations and normal to raised SHBG concentrations. Serum testosterone concentrations determined with two radioimmuno...

  9. Nicotine decreases ethanol-induced dopamine signaling and increases self-administration via stress hormones

    National Research Council Canada - National Science Library

    Doyon, William M; Dong, Yu; Ostroumov, Alexey; Thomas, Alyse M; Zhang, Tao A; Dani, John A

    2013-01-01

    .... Blocking stress hormone receptors prior to nicotine exposure prevented all interactions with alcohol that we measured, including the increased inhibition onto dopamine neurons, the decreased dopamine...

  10. Decreased Libido

    Science.gov (United States)

    ... such as those taken for prostate cancer) Excessive alcohol use or recreational drug use Excessive fatigue Systemic illness (such as chronic lung, heart, kidney and liver failure, cancer) Low testosterone (male hypogonadism) Depression Relationship problems What is the treatment for decreased libido? ...

  11. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taira, Al V. [Western Radiation Oncology, Mountain View, CA (United States); Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV (United States); Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A. [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV (United States); Wallner, Kent E. [Puget Sound Healthcare Corporation Group Health Cooperative, University of Washington, Seattle, WA (United States)

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

  12. Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1.

    Science.gov (United States)

    Radonjić, Nevena V; Jakovcevski, Igor; Bumbaširević, Vladimir; Petronijević, Nataša D

    2013-06-01

    Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl D-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human. A growing body of evidence suggests that alterations in γ-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia. Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits. The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus. Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline. Morphological studies and determination of NRG-1 expression were performed at P70. We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls. For the first time, we show the reduced density of reelin- and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP. Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG. We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus. Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.

  13. Testosterone and the Heart.

    Science.gov (United States)

    Goodale, Travis; Sadhu, Archana; Petak, Steven; Robbins, Richard

    2017-01-01

    Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

  14. [Testosterone deficiency, metabolic syndrome and diabetes mellitus].

    Science.gov (United States)

    Fernández-Miró, Mercè; Chillarón, Juan J; Pedro-Botet, Juan

    2016-01-15

    Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  15. Blood Test: Testosterone

    Science.gov (United States)

    ... a Voice in Health Care Decisions Blood Test: Testosterone KidsHealth > For Parents > Blood Test: Testosterone Print A A A What's in this article? ... Análisis de sangre: testosterona What It Is A testosterone test measures the blood level of the male ...

  16. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

    DEFF Research Database (Denmark)

    Brust, P; Christensen, Thomas; Diemer, Nils Henrik

    1992-01-01

    of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  17. Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats.

    Science.gov (United States)

    Kangiser, Megan M; Dwoskin, Linda P; Zheng, Guangrong; Crooks, Peter A; Stairs, Dustin J

    2017-08-31

    Methamphetamine is a potent psychostimulant with high abuse rates. Currently, there is no Food and Drug Administration-approved pharmacotherapy for methamphetamine addiction. Ideally, a pharmacotherapy should selectively decrease methamphetamine self-administration without affecting responding for other reinforcers. One way to test this is with the use of a multiple schedule of reinforcement, in which drug and food are available in alternating components within a session. The present study evaluated GZ-793A, a vesicular monoamine transporter-2 inhibitor, and varenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptors, for their ability to decrease methamphetamine and food self-administration using a multiple schedule of reinforcement. Male Sprague-Dawley rats self-administered methamphetamine (0.03 mg/kg/intravenous infusion) and food pellets under a multiple schedule of reinforcement. GZ-793A or varenicline was administered before multiple schedule sessions. GZ-793A (5 and 20 mg/kg) significantly decreased methamphetamine intake compared with saline and did not alter food-maintained responding. In contrast, varenicline decreased methamphetamine intake less specifically across time. The results suggest that vesicular monoamine transporter-2 inhibition may be a viable pharmacological target for the treatment of methamphetamine-use disorders.

  18. Detection of testosterone administration based on the carbon isotope ratio profiling of endogenous steroids: international reference populations of professional soccer players.

    Science.gov (United States)

    Strahm, E; Emery, C; Saugy, M; Dvorak, J; Saudan, C

    2009-12-01

    The determination of the carbon isotope ratio in androgen metabolites has been previously shown to be a reliable, direct method to detect testosterone misuse in the context of antidoping testing. Here, the variability in the 13C/12C ratios in urinary steroids in a widely heterogeneous cohort of professional soccer players residing in different countries (Argentina, Italy, Japan, South Africa, Switzerland and Uganda) is examined. Carbon isotope ratios of selected androgens in urine specimens were determined using gas chromatography/combustion/isotope ratio mass spectrometry (GC-C-IRMS). Urinary steroids in Italian and Swiss populations were found to be enriched in 13C relative to other groups, reflecting higher consumption of C3 plants in these two countries. Importantly, detection criteria based on the difference in the carbon isotope ratio of androsterone and pregnanediol for each population were found to be well below the established threshold value for positive cases. The results obtained with the tested diet groups highlight the importance of adapting the criteria if one wishes to increase the sensitivity of exogenous testosterone detection. In addition, confirmatory tests might be rendered more efficient by combining isotope ratio mass spectrometry with refined interpretation criteria for positivity and subject-based profiling of steroids.

  19. Chronic administration of OB protein decreases food intake by selectively reducing meal size in female rats.

    Science.gov (United States)

    Eckel, L A; Langhans, W; Kahler, A; Campfield, L A; Smith, F J; Geary, N

    1998-07-01

    The mechanisms by which OB protein controls food intake and energy balance are unknown. Therefore, we investigated the effects of a novel modified human recombinant OB protein (Mod-OB) on spontaneous feeding patterns, body weight, running wheel activity, and ovarian cycling in female rats. Mod-OB or vehicle was injected (4 mg . kg-1 . day-1 sc) for 2 ovarian cycles (8 days) using a within-subjects design. Observations were continued for five ovarian cycles after injections; treatments were then reversed. Mod-OB reduced food intake approximately 20% from injection day 1 to postinjection day 2. Body weight was reduced from injection day 3 to postinjection day 15 (maximum decrease, 25 +/- 4 g, postinjection days 3 and 4). Food intake was reduced due to decreases in nocturnal meal size, which appeared to be superimposed on the normal pattern of spontaneous feeding (i.e., reductions in meal size at estrus). Mod-OB did not significantly affect diurnal food intake or meal patterns, failed to alter wheel running, and did not disrupt the rats' ovarian cycles. We conclude that chronically administered Mod-OB reduces food intake in female rats by selectively affecting the mechanisms controlling meal size.

  20. Decreased cerebral blood flow after administration of sodium bicarbonate in the distressed newborn infant

    DEFF Research Database (Denmark)

    Lou, H C; Lassen, N A; Fris-Hansen, B

    1978-01-01

    In the course of our studies on cerebral blood flow in newborn infants, we have observed a striking depressing effect of sodium bicarbonate infusion on cerebral blood flow which in some cases may severely aggravate cerebral ischemia. We measured cerebral blood flow before and after the treatment...... with 1 to 8 meqs of sodium bicarbonate in seven distressed newborn infants. The 133 Xe clearance technique was used. The results showed in six of the seven cases a decrease in cerebral blood flow, which in most cases was reduced to 14 to 22 ml/100 g/min, which is about half the value prior...... to the bicarbonate infusion. In one case an extreme reduction occurred: cerebral blood flow was reduced to 3 ml/100 g/min, well below the level compatible with tissue survival. The results are discussed with regard to the optimal treatment of the acidotic newborn....

  1. Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women

    NARCIS (Netherlands)

    Honk, E.J. van; Schutter, D.J.L.G.; Hermans, E.J.; Putman, P.L.J.; Tuiten, A.; Koppeschaar, H.P.F.

    2004-01-01

    Animal research has demonstrated reductions in punishment sensitivity and enhanced reward dependency after testosterone administration. In humans, elevated levels of testosterone have been associated with violent and antisocial behavior. Interestingly, extreme forms of violent and antisocial

  2. Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

    Directory of Open Access Journals (Sweden)

    Daiane B. Fraga

    2013-09-01

    Full Text Available Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF levels in rats subjected to ketamine administration (25 mg/kg for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug.

  3. Testosterone ethosomes for enhanced transdermal delivery.

    Science.gov (United States)

    Ainbinder, Denize; Touitou, Elka

    2005-01-01

    Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm(2). This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.

  4. Use of parenteral testosterone in hypospadias cases

    Directory of Open Access Journals (Sweden)

    Vikram Satav

    2015-01-01

    Full Text Available Objectives: The aim was to evaluate the effect of parenteral testosterone on penile length, preputial hood, vascularity of dartos pedicle in patients with hypospadias. Materials and Methods: A total of 42 patients with hypospadias were included in this study. Injection aquaviron (oily solution each ml containing testosterone propionate 25 mg was given deep intramuscularly in three doses with an interval of 3 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Preoperatively penile length, transverse preputial width and diameter at the base of the penis were measured. Basal testosterone levels were obtained before the institution of therapy and on the day of operation. Results: Following parenteral testosterone administration, the mean increase in penile length, transverse preputial width and diameter at the base of penis was 1.01 ± 0.25 cm (P < 0.001, 1.250 ± 0.52 cm and 0.61 ± 0.35 cm, respectively, (P < 0.001. Serum testosterone level after injection was well within normal range for that age. Conclusion: Parenteral testosterone increased phallus size, diameter and prepuce hypertrophy without any adverse effects. However, due to lack of a control group we cannot make any inferences. Controlled studies are required to establish the benefits of parenteral testosterone.

  5. Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

    National Research Council Canada - National Science Library

    Guowei Pan; Tomoyuki Hanaoka; Mariko Yoshimura; Shujuan Zhang; Ping Wang; Hiromasa Tsukino; Koichi Inoue; Hiroyuki Nakazawa; Shoichiro Tsugane; Ken Takahashi

    2006-01-01

    ..., follicle-stimulating hormone, free testosterone (fT), and estradiol. Methods: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP...

  6. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Weiner, H L; Lemere, C A; Maron, R

    2000-01-01

    Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated ......Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease......-implicated proteins can induce antigen-specific anti-inflammatory immune responses in mucosal lymphoid tissue which then act systemically. We hypothesized that chronic mucosal administration of Abeta peptide might induce an anti-inflammatory process in AD brain tissue that could beneficially affect......-Abeta antibodies of the IgG1 and IgG2b classes, and mononuclear cells in the brain expressing the anti-inflammatory cytokines interleukin-4, interleukin-10, and tumor growth factor-beta. Our results demonstrate that chronic nasal administration of Abeta peptide can induce an immune response to Abeta that decreases...

  7. Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

    Science.gov (United States)

    Smith, Mark A; Fronk, Gaylen E; Abel, Jean M; Lacy, Ryan T; Bills, Sarah E; Lynch, Wendy J

    2018-02-02

    Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

  8. Effect of Testosterone on Hepcidin, Ferroportin, Ferritin and Iron Binding Capacity in Patients with Hypogonadotropic Hypogonadism and Type 2 Diabetes

    Science.gov (United States)

    DHINDSA, SANDEEP; GHANIM, HUSAM; BATRA, MANAV; KUHADIYA, NITESH D.; ABUAYSHEH, SANAA; GREEN, KELLY; MAKDISSI, ANTOINE; CHAUDHURI, AJAY; DANDONA, PARESH

    2016-01-01

    Context Since the syndrome of hypogonadotropic hypogonadism (HH) is associated with anemia and the administration of testosterone restores hematocrit to normal, we investigated the potential underlying mechanisms. Design Randomized, double blind, placebo controlled trial Methods We measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. 44 men had HH (defined as subnormal free testosterone along with low or normal LH concentrations) while 50 were eugonadal. Men with HH were randomized to testosterone or placebo treatment every 2 weeks for 15 weeks. Blood samples were collected at baseline, 3 and 15 weeks after starting treatment. 20 men in testosterone group and 14 men in placebo group completed the study. Results Hematocrit levels were lower in men with HH (41.1±3.9% vs. 43.8±3.4%, p=0.001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin or iron, or in the expression of ferroportin or TR in MNC among HH and eugonadal men. Hematocrit increased to 45.3±4.5%, hepcidin decreased by 28±7% and erythropoietin increased by 21±7% after testosterone therapy (ptestosterone therapy. Conclusions The increase in hematocrit following testosterone therapy is associated with an increase in erythropoietin, the suppression of hepcidin, and an increase in the expression of ferroportin and transferrin receptor. PMID:27292585

  9. Effect of Testosterone on Carrageenone Induced Inflammation in Gonadectomized Male Rats

    Directory of Open Access Journals (Sweden)

    A Zarifkar

    2009-07-01

    Full Text Available ABSTRACT: Introduction & Objective: Different nociceptive and inflammatory responses to noxious stimuli in male and female animals imply that sex hormones may affect on inflammatory factors, induction and intensity of the inflammation. The aim of the current study was to evaluate the effect of testosterone administration on carrageenone induced inflammation in gonadectomized male rats. Materials & methods: Forty male Wistar rats were divided into four groups (n=8. 1-The control rats without receiving any drug or surgical operation. 2-The sham – operated animals with surgical stress. 3-The gonadectomized rats, receiving 0.5 ml vehicle (olive oil i.p. 4-The gonadectomized rats, receiving testosterone enantate (6 mg/100 gr body weight in 0.5 ml vehicle i.p.. At the sixth day of gonadectomy operation, inflammation was induced by injection of 1% carrageenone in the right hind paw of rats. Edematous paw volume as an index of inflammation was determined by immersing it into the mercury container. Weight of paw in the mercury was measured and then the paw volume was calculated in relation to specific gravity of mercury (13.6gm/ml. Data were statistically analyzed by SPSS software using ANOVA. Results: The results showed that edematous paw volume significantly was reduced in testosterone enantate administrated gonadectomized rats compared to the control group (P<0.01. Conclusion: It can be concluded that high dose of testosterone causes attenuation of inflammatory response. The testosterone anti-inflammatory effect is probably due to inhibition of inflammatory factors (Interleukins production or decrease in receptors of inflammatory factors. Keywords: Testosterone, Carrageenone, Inflammation, Rats

  10. SB223412, a neurokinin-3 receptor-selective antagonist, suppresses testosterone secretion in male guinea pigs.

    Science.gov (United States)

    Nakamura, Sho; Ito, Yoshiko; Yamamoto, Koki; Takahashi, Chudai; Dai, Mingdao; Tanahashi, Miyu; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Oishi, Shinya; Maeda, Kei-Ichiro; Matsuda, Fuko

    2017-10-15

    Guinea pigs are important zoo animals and have been recommended for animal-assisted activities or therapy, however there are problems concerning testosterone inducing aggressive or sexual behaviors in male guinea pigs. Testicular testosterone secretion is regulated by pulsatile gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release in mammals. The mechanism generating GnRH/LH pulses is thought to be governed by kisspeptin neurons, which coexpress neurokinin B (NKB) and dynorphin A (Dyn), in the arcuate nucleus (ARC). Kisspeptin neurons in the ARC are frequently referred to as KNDy neurons. The purpose of this study was to examine whether the antagonization of NKB-neurokinin-3 receptor (NK3R) signaling can manipulate testosterone secretion in male guinea pigs. A single subcutaneous administration or 7 days of oral administration of an NK3R-selective antagonist, SB223412 (50 mg/body), significantly decreased plasma testosterone levels in male guinea pigs. In vitro binding assays confirmed that SB223412 has a high affinity to guinea pig NK3R. These results suggest that SB223412 could be used as an orally-available compound to suppress testosterone levels in male guinea pigs. Double labeling in situ hybridization of kisspeptin and either NKB or Dyn showed that kisspeptin-expressing neurons contained NKB (77.9%) or Dyn (62.3%) in the ARC, suggesting the presence of KNDy neurons in the ARC of guinea pigs. In conclusion, the present study shows that SB223412 could be a candidate compound to suppress testosterone secretion in male guinea pigs for controlling sexual and aggressive behaviors in the species. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Testosterone Deficiency and Nocturia: A Review

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shigehara

    2017-04-01

    Full Text Available Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS, and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions.

  12. Diagnosis and management of testosterone deficiency

    Science.gov (United States)

    McBride, James A; Carson, Culley C; Coward, Robert M

    2015-01-01

    Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD. PMID:25532575

  13. Testosterone Deficiency and Nocturia: A Review.

    Science.gov (United States)

    Shigehara, Kazuyoshi; Izumi, Koji; Mizokami, Atsushi; Namiki, Mikio

    2017-04-01

    Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS), and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT) is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions. Copyright © 2017 Korean Society for Sexual Medicine and Andrology.

  14. Protection of male reproductive toxicity in rats exposed to di-n-butyl phthalate during embryonic development by testosterone.

    Science.gov (United States)

    Giribabu, Nelli; Reddy, Pamanji Sreenivasula

    2017-03-01

    Di-n-butyl phthalate (DBP) widely spread industrial chemical that made drastic alteration in male reproductive system. The present study elucidates the protective role of testosterone on reproductive toxicity in prenatal DBP exposed adult male rats. Pregnant rats were injected with corn oil or 100 and 500mg/kg body weight of DBP on gestation day (GD) 1, 7 and 14. F1 male rats were weaned, injected with either testosterone or vehicle. On postnatal day (PND) 100 F1 adult male rats were cohabited with untreated female rats. Then rats were sacrificed and analyzed for other reproductive end points. Prenatal DBP exposed male rat testes, seminal vesicle weight, sperm count, motility, viability and HOS tail coiled sperm were significantly decreased with increased sperm morphological abnormalities. The levels of testicular 3β, 17βHSD, serum testosterone were significantly decreased with increased FSH, LH levels in experimental rats. The fertility studies revealed that increased pre, post-implantation losses and resorptions in normal females cohabited with experimental rats. Higher testicular LPO with lower SOD, CAT and GPx activity levels in experimental rats. Administration of testosterone to prenatal DBP treated male rats showed significant protection in above all parameters. In conclusions, testosterone deteriorates prenatal DBP induced reproductive and fertility toxicity by decreased oxidative stress and increased testicular antioxidant enzymes. Copyright © 2016. Published by Elsevier Masson SAS.

  15. Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats.

    Science.gov (United States)

    Vilskersts, Reinis; Kuka, Janis; Svalbe, Baiba; Cirule, Helena; Liepinsh, Edgars; Grinberga, Solveiga; Kalvinsh, Ivars; Dambrova, Maija

    2011-01-01

    Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronate, an inhibitor of L-carnitine biosynthesis, or their combination on the development of hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Experimental animals were divided into five groups and treated for 8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at the doses above (n = 10). During the experiment, control group animals continued to consume a diet with normal salt content. Administration of the combination significantly improved the survival rate for 50% of the population. None of the tested compounds or their combination influenced high salt intake-induced hypertension, while treatment with mildronate and the combination for 8 weeks significantly decreased resting heart rate by 12% and 10%, respectively. Feeding with high salt diet had no influence on systolic function of the heart, but it induced thickening of the ventricular walls and development of heart hypertrophy that was not improved by the administration of tested compounds. In addition, administration of the combination attenuated the development of endothelial dysfunction in isolated aortic rings. In conclusion, our results demonstrate that treatment with a combination of L-carnitine and mildronate is protective against hypertension-induced complications in an experimental model of salt-induced hypertension.

  16. Protection against vanadium-induced testicular toxicity by testosterone propionate in rats.

    Science.gov (United States)

    Chandra, Amar K; Ghosh, Rituparna; Chatterjee, Aparajita; Sarkar, Mahitosh

    2010-07-01

    Vanadium is a well recognized industrial hazard known to adversely affect male reproductive functions. The intricate mechanistic aspects of this metal and the role of oxidative stress in the deterioration of testicular functions are investigated in the current study. The experiment also focused on the effects of testosterone propionate in testicular and sperm functions in the rat intoxicated with vanadate. Vanadium exposure resulted in a more prominent spermatogenic arrest and consistently abolished the conversion of round to mature spermatids along with decreased epididymal sperm number and increased percentage of abnormal sperm. This is followed by a precipitous decline in the level of serum testosterone and gonadotropins and consequently the testicular steroidogenic and antioxidant enzymes were inhibited. Vanadium induces degeneration in the genital organs of rats and exhibits high indices of lipid oxidative damage. In response to exogenous testosterone propionate (TP) administration, spermatogonial cell populations remained suppressed, while the spermatogenesis was restored quantitatively. In contrast, the hormone treatment had no effect on the dramatically decreased serum FSH level after vanadate treatment. Moreover, TP could ameliorate the toxicity, as indicated by decreased testicular lipid peroxidation with marginal but significant increase in the activities of all the measured enzymes following vanadate-treatment. Taken together all these studies establish that vanadium is a testicular toxicant that perturbs the male reproductive system adversely. However, hormone replacement therapy by testosterone propionate may provide partial protection. The results suggest the feasibility of using endocrine regimens to impede deleterious effects of vanadium on the male reproductive system.

  17. Low testosterone levels may be associated with suicidal behavior in older men while high testosterone levels may be related to suicidal behavior in adolescents and young adults: a hypothesis.

    Science.gov (United States)

    Sher, Leo

    2013-01-01

    Several lines of evidence suggest that there is an association between testosterone and suicidal behavior. A link between testosterone and the neurobiology of suicidal behavior may be related to: a) a direct effect of testosterone on suicidality via certain brain mechanisms; and/or b) a testosterone influence on aggression and, consequently, suicidality; and/or c) a testosterone effect on mood and, consequently, suicidality; and/or d) a testosterone effect on cognition and, consequently, suicidality. At least one study has demonstrated a relation between high levels of testosterone and suicide in young people. A significant number of studies suggest that high testosterone levels are associated with aggression in adolescents and adults. Multiple lines of evidence indicate that aggression is associated with suicidal behavior. The effect of high testosterone levels on suicidality in adolescents and young adults may be mediated by testosterone-related elevated aggression. It is also possible that, in young people, high testosterone levels are directly linked to suicidality via certain brain mechanisms. In older men, decreased testosterone levels are associated with depressive symptoms and reduced cognitive function, whereas higher blood levels of testosterone are associated with better mood and cognitive functioning. Depression and reduced cognition are associated with suicidal behavior and may mediate the effect of decreased testosterone levels on suicidality. Therefore, it is reasonable to propose that suicidal behavior in adolescents and young adults is associated with high testosterone levels, whereas suicidality in older men is associated with decreased testosterone secretion.

  18. Experimental Manipulation of Corticosterone Does Not Influence the Clearance Rate of Plasma Testosterone in Birds.

    Science.gov (United States)

    Deviche, Pierre; Desaivre, Stève; Giraudeau, Mathieu

    In vertebrates, exposure to acute stressors stimulates the secretion of adrenal glucocorticoids such as corticosterone, and in some situations this hormone plays an important role in orchestrating the trade-off that exists between reproduction and self-maintenance. Stressful conditions often lead to a decrease in plasma levels of sex steroids such as testosterone in males, and it has been hypothesized that corticosterone contributes to this decrease. Generally supporting this proposition, glucocorticoids can inhibit the reproductive axis activity at multiple levels, including direct effects on testicular endocrine function. Here we tested for the first time the additional hypothesis that stress-induced glucocorticoids are associated with an increased clearance rate of circulating testosterone. To test this hypothesis, we performed two experiments comparing changes in plasma testosterone as a function of time (6-60 min) after a single injection of this hormone into captive male house finches (Haemorhous mexicanus) that either were intact (controls) or were pharmacologically adrenalectomized by administration of the glucocorticoid synthesis inhibitor mitotane. Control finches rapidly elevated their plasma corticosterone in response to handling, whereas mitotane treatment abolished this response by approximately 95%. Contrary to our prediction, we found no clear evidence that control birds eliminated exogenous testosterone from circulation at a different rate than pharmacologically adrenalectomized finches. These findings do not support the hypothesis that, during acute stress, elevated plasma glucocorticoids stimulate the clearance rate of testosterone. The rapid inhibitory effect of stress on plasma testosterone may rather result from direct actions of glucocorticoids on the gonadal production of the androgen or involve a glucocorticoid-independent mechanism.

  19. KAJIAN TERAPI AKUPUNKTUR TERHADAP KADAR HORMON TESTOSTERON PRIA USIA LANJUT

    Directory of Open Access Journals (Sweden)

    Bambang Wasito Tjipto

    2012-12-01

    Full Text Available Background: Testosterone was the most important androgen secreted into the blood in males. It was responsible for development of secondary male sex characteristics and its measurements are helpful in evaluating the hypogonadal states. Decreasing of testosterone in males started in middle age, about 45–59 years old. It is responsible of decreasing muscle mass and strength, increasing of body fat especially abdominal fat and gynecomastia, less of libido and sexual intercourse frequency, increase of erectile dysfunction. Objective: The objective of this study was conducted stimulation on acupuncture reproduction point to increase testosterone hormone level in elder’s men. Methods: The study used non randomized experiment pre- post test without control group design, the samples was 40 older men, about 50 – more than 70 years old. The stimulation on acupuncture point CV-4, Sp-6, LV-3, and ST-36, on older men were given five times per week, for ten treatments, before treatment each patient was determined the concentration of testosterone hormone and after ten times acupuncture treatment. Results: 15 old men, have increased testosterone level, 20 old men have decreased testosterone level, and 16 old men have no changes in libido after ten times acupuncture treatment. Not all responder after therapy acupuncture ten times at reproduction point have increased of hormone testosterone. Most of 50–69 year men have increased testosterone level. Men above 70 year have no changes testosterone level. There were 24 old men have changes in libido without increased testosterone level. Conclusion: acupuncture may used as alternative therapy to increased testosterone level and libido for elderly men. Key words: Acupuncture, testosterone hormone, old men

  20. Positive Modulation of GABAB Receptors Decreased Nicotine Self-administration and Counteracted Nicotine-induced Enhancement of Brain Reward Function in Rats

    OpenAIRE

    Paterson, Neil E.; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-01-01

    Acute administration of γ-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration, and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABAB receptor positive modulators may represent potentially improved therapeutic compounds because of their fewer side-effects than receptor agonists. The present study investigated the effects of administration of the GABAB receptor positive modulators 2,6-Di...

  1. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men

    Directory of Open Access Journals (Sweden)

    Gårevik N

    2014-12-01

    Full Text Available Nina Gårevik, Anders Rane, Linda Björkhem-Bergman, Lena Ekström Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Aims: To study the effect and time profile of different doses of testosterone enanthate on the blood lipid profile and gonadotropins. Experimental design: Twenty-five healthy male volunteers aged 27–43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses of Testoviron® Depot. Luteinizing hormone (LH, follicle-stimulating hormone (FSH, blood lipid profile (total cholesterol, plasma [p-] low-density lipoprotein, p-high-density lipoprotein [HDL], p-apolipoprotein A1 [ApoA1], p-apolipoprotein B, p-triglycerides, p-lipoprotein(a, serum [s-] testosterone, and 25-hydroxyvitamin D3 were analyzed prior to, and 4 and 14 days after dosing. Testosterone and epitestosterone in urine (testosterone/epitestosterone ratio were analyzed prior to each dose after a washout period of 6–8 weeks. Results and discussion: All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic–pituitary–gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg did not have any effect on the lipid profile. Conclusion: The single doses of testosterone produced a dose-dependent increase in serum testosterone concentrations together with suppression of s-LH and s-FSH. Alterations in ApoA1 and HDL were observed after the two highest single doses. It is possible that long-time abuse of anabolic androgenic steroids will lead to alteration in vitamin D status

  2. Testosterone affects language areas of the adult human brain

    NARCIS (Netherlands)

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-01-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in

  3. Hypogonadism and testosterone replacement theraphy: the controversy and the evidence

    National Research Council Canada - National Science Library

    2007-01-01

    ... with energy loss; impaired cognition; decreased bone density, muscle mass, and strength; and sexual dysfunction. (2) In addition, low serum testosterone levels have been linked with an adverse metabolic profile and increased mortality of all causes (3,4) Testosterone replacement therapy (TRT) is available in several formulations that are approved by ...

  4. A cohort effect on serum testosterone levels in Finnish men

    DEFF Research Database (Denmark)

    Perheentupa, A; Mäkinen, J; Laatikainen, T

    2013-01-01

    To investigate whether a population-level decline in serum testosterone exists in Finnish men. In comparison with other European populations, Finnish men have compared well in the studies of reproductive health (i.e. semen quality, incidence of cryptorchidism and testicular cancer); thus, we...... expected no significant cohort-dependent decrease in serum testosterone....

  5. DDT increases hepatic testosterone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sierra-Santoyo, Adolfo; Albores, Arnulfo; Cebrian, Mariano E. [Cinvestav-IPN, Seccion de Toxicologia, Mexico (Mexico); Hernandez, Manuel [Cinvestav-IPN, Departamento de Biologia Celular (Mexico)

    2005-01-01

    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-{sup 14}C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2{alpha}-hydroxytestosterone (OHT), and 16{alpha}-OHT but higher 6{beta}-OHT whereas treated females produced less 7{alpha}-OHT and AD but higher 6{beta}-OHT and 6{alpha}-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6{beta}-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6{alpha}-/15{alpha}-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6{alpha}-/16{alpha}-OHT and 6-dehydrotestosterone/16{alpha}-OHT ratios followed a similar tendency, with the ratio 6{alpha}-/16{alpha}-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats. (orig.)

  6. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  7. Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

    Science.gov (United States)

    Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2014-01-01

    Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

  8. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

    Directory of Open Access Journals (Sweden)

    Shu-Ting Chan

    2014-01-01

    Full Text Available Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week. Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

  9. Interaction between testosterone and growth hormone on whole-body protein anabolism occurs in the liver.

    Science.gov (United States)

    Birzniece, Vita; Meinhardt, Udo J; Umpleby, Margot A; Handelsman, David J; Ho, Ken K Y

    2011-04-01

    GH and testosterone both exert protein-anabolic effects and may act synergistically. Liver and muscle are major sites of protein metabolism. Our objective was to determine whether the site of GH and testosterone interaction on protein metabolism is primarily hepatic or extrahepatic. In this open-label randomized crossover study, the impact on whole-body protein metabolism of oral (solely hepatic testosterone exposure) and transdermal (systemic testosterone exposure) testosterone replacement in the presence or absence of GH was compared. Eleven hypopituitary men with GH and testosterone deficiency were randomized to 2-wk treatments with transdermal testosterone (10 mg) or oral testosterone (40 mg), with or without GH replacement (0.6 mg/d). The dose of testosterone administered orally achieves physiological portal testosterone concentrations without spillover into the systemic circulation. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown, and leucine oxidation (Lox), a measure of irreversible protein loss, were estimated at the end of each treatment. In the absence of GH, neither transdermal nor oral testosterone affected LRa or Lox. GH therapy significantly increased LRa, an effect equally reduced by transdermal and oral testosterone administration. GH replacement alone did not significantly change Lox, whereas addition of testosterone treatment reduced Lox, with the effect not significantly different between transdermal and oral testosterone. In the doses used, testosterone stimulates protein anabolism by reducing protein breakdown and oxidation only in the presence of GH. Because the net effect on protein metabolism during GH therapy is not different between systemic and solely hepatic testosterone administration, we conclude that the liver is the primary site of this hormonal interaction.

  10. Serum testosterone concentrations in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C

    1987-01-01

    Median serum testosterone concentration of men with alcoholic cirrhosis (n = 216) did not differ significantly from normal controls (n = 51), but serum testosterone concentrations varied by a factor 43.9 in patients compared to 3.2 in controls (P less than .001). Nineteen percent of the patients...... had serum testosterone concentrations above 30 nmol/L. Serum concentrations of sex-hormone-binding globulin (SHBG) were significantly (P less than .001) raised, and serum concentrations of calculated nonprotein-bound and non-SHBG-bound testosterone were significantly (P less than .001) decreased...... in patients compared to normal control values. A number of background variables were analyzed with reference to serum testosterone concentrations by means of multiple regression techniques after having divided the patients into groups (A, B, C) with decreasing liver function by a modification of the Child...

  11. Intracoronary administration of levosimendan in patients with acute coronary syndromes and decreased left ventricular ejection fraction undergoing coronary artery bypass graft surgery

    OpenAIRE

    CAREV, MLADEN; MARINOV, VJERA; Karanovic, Nenad; Bulat, Cristijan; KOCEN, DUBRAVKA; Lojpur, Mihajlo; COVIC, ZDENKO; IVANCEV, BOZENA; PARCINA, ZVONIMIR

    2017-01-01

    In cardiac surgery patients, intracoronary (IC) administration of levosimendan can provide optimal drug spread, enabling effective manifestation of favorable drug effects and avoiding potentially harmful systemic hypotension. This could be beneficial in acute coronary syndromes (ACS) with decreased left ventricular ejection fraction (LVEF). We present ten cases of IC administration of levosimendan in ACS manifested as ST segment elevation myocardial infarction...

  12. Administration

    OpenAIRE

    2009-01-01

    Cet imposant volume constitue un registre des cours magistraux tenus par l’auteur à l’École supérieure allemande des sciences administratives de Spire, enrichis des résultats de travaux scientifiques menés principalement à l'Institut Allemand de Recherche en Administration Publique (Deutsches Forschungsinstitut für öffentliche Verwaltung Speyer, FÖV). Il s’agit donc d’une entreprise au long cours, destinée à apporter un nouvel éclairage (quasi ?) exhaustif sur l’administration publique : son ...

  13. Systemic PD149163, a neurotensin receptor 1 agonist, decreases methamphetamine self-administration in DBA/2J mice without causing excessive sedation.

    Directory of Open Access Journals (Sweden)

    Amanda L Sharpe

    Full Text Available Methamphetamine (METH is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area. Previous studies in rats suggest that neurotensin agonism decreases METH self-administration, but these studies did not examine the effect of neurotensin agonism on the pattern of self-administration or open field locomotion. In our studies, we established intravenous METH self-administration in male, DBA/2J mice (fixed ratio 3, 2 hr sessions and examined the effect of pretreatment with the NTS1 receptor agonist PD149163 on METH self-administration behavior. Locomotion following PD149163 was also measured up to 2 hours after injection on a rotarod and in an open field. Pretreatment with PD149163 (0.05 and 0.10 mg/kg, s.c. significantly decreased METH self-administration. The pattern of responding suggested that PD149163 decreased motivation to self-administer METH initially in the session with more normal intake in the second hour of access. Voluntary movement in the open-field was significantly decreased by both 0.05 and 0.10 mg/kg (s.c. PD149163 from 10-120 minutes after injection, but rotarod performance suggested that PD149163 did not cause frank sedation. These results suggest that a systemically delivered NTS1 receptor agonist decreases METH self-administration in mice. The pattern of self-administration suggests that PD149163 may acutely decrease motivation to self-administer METH before the drug is experienced, but cannot rule out that depression of voluntary movement plays a role in the decreased self-administration.

  14. Orally co-administrated oleo-gum resin of Commiphora myrrha decreases the bioavailability of cyclosporine A in rats.

    Science.gov (United States)

    Al-Jenoobi, F I; Alam, M A; Al-Mohizea, A M; Ahad, A; Raish, M

    2015-08-01

    Cyclosporine A is a narrow therapeutic indexed immunosuppressant used after organ transplantation. Several herbs have been reported to alter its pharmacokinetics. Myrrh, dried oleogum resin obtained from Commiphora myrrha (Burseraceae) has been used for many common ailments. The present study was carried out to investigate the effect of myrrh on the pharmacokinetics of cyclosporine A. The rats of the control group received 60 mg/kg, p.o. cyclosporine A, and blood samples were collected at predetermined time intervals. Rats of the test group were treated with an aqueous suspension of myrrh (380 mg/kg p.o.) for eight days and on 8th day a single dose of cyclosporine A was administered to the treated group after 1 h of myrrh administration. Blood samples were drawn at predetermined time points and the drug was analyzed in whole blood by using H-Class UPLC-TQD. Pharmacokinetic profiles of control and test group were compared. Statistically significant differences were observed between the pharmacokinetic parameters of control and treated groups. In the myrrh treated group, the AUC(0-t) and C(max) of cyclosporine A was decreased by about 45% and 48%, respectively. The time to reach maximum concentration (T(max)) remained almost unchanged in both groups. Results indicated that the bioavailability of cyclosporine A was reduced by about 45% when co-administered with myrrh. This observation suggests that concurrent consumption of myrrh and cyclosporine A should be avoided. To confirm the clinical relevance of these findings, P-gp and CYP3A based molecular investigations can be performed along with a well-planned clinical study.

  15. Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

    Science.gov (United States)

    Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

    2016-08-01

    Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Decreased brain serotonin turnover rate following administration of Sharbat-e-Ahmed Shah produces antidepressant and anxiolytic effect in rats.

    Science.gov (United States)

    Ahmed, Muhammad; Azmat, Aisha

    2017-07-07

    Sharbat-e-Ahmed Shah (SAS) has usually been used in Traditional Unani Medicine (TUM) for depression and insomnia but still not evaluated for its anti-depressant and Neuropharmacological activity. In the present study, a Human dose of SAS (0.6 ml/kg/d) was administered orally to the rats for 15 consecutive days. Antidepressant and anxiolytic were screened scientifically in rats by using Forced swim test and light and dark box test. At the end of study high-performance liquid chromatographic (HPLC) method with electrochemical (EC) detector was used for the measurement of blood and brain tryptophan and brain serotonin levels. The present reported results are according to what is known in TUM, where is prescribed as an antidepressant agent. After the administration, SAS (at a human dose for 15 days) reduced the immobility time in rats analogous to Imipramine (positive control) indicating the antidepressant effect of SAS. In the present study, Diazepam or SAS (0.6 ml/kg/day) treated rats stayed in the illuminated side of the light-dark box, as compare to control rats (Veh, 134.62 ± 4.430 s; SAS 0.6 ml/kg, 192.2 ± 8.11 s; DZP 1.0 mg/kg, 205.21.20 ± 10.26 s, p < 0.05). It was also observed that SAS increased the availability of tryptophan in blood and brain and hence increases 5-hydroxytryptamine (Serotonin: 5HT) in the brain. At the end, it was concluded that SAS contains some active principles which increase the availability of neurochemical (tryptophan and 5HT) and decrease the 5HT turnover rate thus causes antidepressant and anxiolytic effects in experimental animals.

  17. Could you have low testosterone?

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000722.htm Could you have low testosterone? To use the sharing features on ... Symptoms Some men with low testosterone do not have any symptoms. Others may have: Low sex drive ...

  18. Testosterone replacement does not normalize carcass composition in chronically decerebrate male rats.

    Science.gov (United States)

    Harris, Ruth B S; Kelso, Emily W; Flatt, William P; Grill, Harvey J; Bartness, Timothy J

    2009-06-01

    Chronically decerebrate (CD) rats, in which the forebrain and its descending projections are completely neurally isolated from hindbrain and rostral projections, gain substantial amounts of body fat, lose lean tissue, and have low circulating testosterone concentrations. We tested whether testosterone replacement would normalize body composition of male CD rats. Five groups of rats were used: CD placebo, CD testosterone, control placebo, castrate placebo, and castrate testosterone. Testosterone replacement was initiated at the first stage of CD surgery in both CDs and castrate controls. The second stage of CD surgery occurred 8 days later, and the study ended 15 days later. Testosterone implants produced 10-fold normal circulating concentrations. Food intake was fixed for all rats by tube feeding. CD rats had substantially more body fat and less lean tissue than neurally intact rats. Testosterone replacement did not affect adiposity of CD rats but did increase carcass water content. Energy expenditure of CD rats was significantly lower than that of control placebo and castrated rats. Testosterone lowered respiratory equivalency ratio and ameliorated a fall in energy expenditure late in the intermeal interval in CD rats. Castration increased, and testosterone decreased luteinizing hormone (LH) and follicle stimulating hormone (FSH) in neurally intact controls. LH was undetectable, and FSH was equivalent to neurally intact controls in CD rats, and neither was affected by testosterone. Collectively, low testosterone did not explain obesity or decreased lean body mass of CD rats, although CD rats exhibited abnormal levels of circulating reproductive hormones and disrupted testosterone negative feedback.

  19. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study.

    Science.gov (United States)

    Wallis, Christopher J D; Lo, Kirk; Lee, Yuna; Krakowsky, Yonah; Garbens, Alaina; Satkunasivam, Raj; Herschorn, Sender; Kodama, Ronald T; Cheung, Patrick; Narod, Steven A; Nam, Robert K

    2016-06-01

    Conflicting evidence exists for the association between testosterone replacement therapy and mortality and cardiovascular events. The US Food and Drug Administration recently cautioned that testosterone replacement therapy might increase risk of heart attack and stroke, based on evidence from studies with short treatment duration and follow-up. No previous study has assessed the effect of duration of testosterone treatment on these outcomes. We aimed to assess the association between long-term use of testosterone replacement therapy and mortality, cardiovascular events, and prostate cancer diagnoses, using a time-varying exposure analysis. We did a population-based matched cohort study of men aged 66 years or older newly treated with testosterone replacement therapy and controls matched for age, region of residence, comorbidity, diabetes status, and index year from 2007-12 in Ontario, Canada, using data from the Ontario Drug Benefit database, the Canadian Institute for Health Information (CIHI) Discharge Abstract Database, the CIHI National Ambulatory Care Reporting System, the Ontario Health Insurance Plan database, the Ontario Myocardial Infarction Database, the Ontario Diabetes Database, the Ontario Cancer Registry, and the Registered Persons database. We assessed the association between cumulative testosterone replacement therapy exposure and mortality, cardiovascular events, and prostate cancer using marginal models with a time-varying testosterone exposure. We included 10 311 men treated with testosterone replacement therapy and 28 029 controls between Jan 1, 2007, and June 30, 2012. Over a median follow-up of 5·3 years (IQR 3·6-7·5) in the testosterone replacement therapy group and 5·1 years (3·4-7·4) in the control group, patients treated with testosterone replacement therapy had lower mortality than did controls (hazard ratio [HR] 0·88, 95% CI 0·84-0·93). Patients in the lowest tertile of testosterone exposure had increased risk of mortality

  20. Testosterone and Cardiovascular Disease

    Science.gov (United States)

    Tambo, Amos; Roshan, Mohsin H.K.; Pace, Nikolai P.

    2016-01-01

    Cardiovascular disease [CVD] is a leading cause of mortality accounting for a global incidence of over 31%. Atherosclerosis is the primary pathophysiology underpinning most types of CVD. Historically, modifiable and non-modifiable risk factors were suggested to precipitate CVD. Recently, epidemiological studies have identified emerging risk factors including hypotestosteronaemia, which have been associated with CVD. Previously considered in the realms of reproductive biology, testosterone is now believed to play a critical role in the cardiovascular system in health and disease. The actions of testosterone as they relate to the cardiac vasculature and its implication in cardiovascular pathology is reviewed. PMID:27014372

  1. Causal relationship between obesity and serum testosterone status in men

    DEFF Research Database (Denmark)

    Eriksson, Joel; Haring, Robin; Grarup, Niels

    2017-01-01

    CONTEXT: Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. OBJECTIVES: Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. DESIGN: Bi-directional Mendelian...... randomization (MR) analysis on prospective cohorts. SETTING: Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden). PARTICIPANTS: 7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs. MAIN OUTCOME MEASURES: BMI and serum...... testosterone adjusted for age, smoking, time of blood sampling and site. RESULTS: 1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2...

  2. Testosterone Replacement Therapy and Polycythemia in HIV-infected Patients

    Science.gov (United States)

    Vorkas, Charles Kyriakos; Vaamonde, Carlos M.; Glesby, Marshall J.

    2013-01-01

    We conducted a case-control study to assess testosterone use as a primary risk factor for polycythemia in 21 HIV-infected men. Any testosterone use within two months of first elevated hemoglobin was associated with polycythemia (matched odds ratio 6.55; 95% CI 1.83-23.4; P=0.004) and intramuscular administration demonstrated a stronger association than topical use. No adverse cardiovascular or thrombotic events were observed. HIV-infected patients taking testosterone should undergo routine hematologic monitoring with adjustment of therapy when appropriate. PMID:22008652

  3. Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Weiping, E-mail: weiping.qin@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States); Cardozo, Christopher, E-mail: Chris.Cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States)

    2010-12-17

    Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis, REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the gastrocnemius

  4. Intrathecal administration of clonidine or yohimbine decreases the nociceptive behavior caused by formalin injection in the marsh terrapin (Pelomedusa subrufa)

    DEFF Research Database (Denmark)

    Makau, Christopher M; Towett, Philemon K; Abelson, Klas S P

    2014-01-01

    BACKGROUND: The role of noradrenergic system in the control of nociception is documented in some vertebrate animals. However, there are no data showing the role of this system on nociception in the marsh terrapins. METHODOLOGY: In this study, the antinociceptive action of intrathecal administration...... of the α 2-adrenoreceptor agonist clonidine and α 2-adrenoreceptor antagonist yohimbine was evaluated in the African marsh terrapin using the formalin test. The interaction of clonidine and yohimbine was also evaluated. RESULTS: Intrathecal administration of clonidine (37.5 or 65 μg/kg) caused...... administration of yohimbine (53 μg/kg) followed immediately by intrathecal injection of the serotonergic methysergide maleate (20 μg/kg) resulted in a significant reversal of the antinociceptive effect of yohimbine. CONCLUSION: The present study documented the intrathecal administration of drugs in the marsh...

  5. Lowered testosterone in male obesity: mechanisms, morbidity and management

    Science.gov (United States)

    Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

    2014-01-01

    With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials. PMID:24407187

  6. Lowered testosterone in male obesity: Mechanisms, morbidity and management

    Directory of Open Access Journals (Sweden)

    Mark Ng Tang Fui

    2014-04-01

    Full Text Available With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.

  7. Lowered testosterone in male obesity: mechanisms, morbidity and management.

    Science.gov (United States)

    Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

    2014-01-01

    With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.

  8. Comparison of methods for determination of testosterone and non-protein bound testosterone in men with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick

    1986-01-01

    The serum concentrations of testosterone and of non-protein bound testosterone were determined in 28 men with alcoholic liver disease having normal to decreased serum albumin concentrations and normal to raised SHBG concentrations. Serum testosterone concentrations determined with two...... radioimmunoassays using different purification procedures and antibody batches did not differ significantly and correlated significantly (r=0.91; p less than 0.001). The median serum concentration of non-protein bound testosterone was 0.265 nmol/l (range 0.068-0.495 nmol/l) when determined by equilibrium dialysis...... and 0.232 nmol/l (range 0.042-0.610 nmol/l) when calculated according to the law of mass action. This difference is insignificant. The concentrations of non-protein bound testosterone determined by the two methods correlated significantly (r=0.83; p less than 0.001). In the calculation of non...

  9. Testosterone: action, deficiency, substitution

    National Research Council Canada - National Science Library

    Nieschlag, E; Nieschlag, S. (Susan); Behre, H. M. (Hermann M.)

    2004-01-01

    ... reviews applications in male contraception, the role of 5 -reductase inhibitors and the controversial use of DHEA. For this book the editors have assembled the world leaders in testosterone research and clinical andrology and endocrinology. A special feature of the book is the fact that its 24 chapters were submitted simultaneously to ens...

  10. Testosterone Transdermal Patch

    Science.gov (United States)

    ... growth, development, and functioning of the male sexual organs and typical male characteristics. Testosterone transdermal patches work ... Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat ...

  11. Testosterone Nasal Gel

    Science.gov (United States)

    ... growth, development, and functioning of the male sexual organs and typical male characteristics. Testosterone works by replacing ... Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat ...

  12. Positive Modulation of GABAB Receptors Decreased Nicotine Self-administration and Counteracted Nicotine-induced Enhancement of Brain Reward Function in Rats

    Science.gov (United States)

    Paterson, Neil E.; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-01-01

    Acute administration of γ-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration, and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABAB receptor positive modulators may represent potentially improved therapeutic compounds because of their fewer side-effects than receptor agonists. The present study investigated the effects of administration of the GABAB receptor positive modulators 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177), and co-administration of the GABAB receptor positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) with the GABAB receptor agonist (3-amino-2[S]-hydroxypropyl)-methylphosphinic acid (CGP44532) on nicotine- and food-maintained responding under fixed-ratio 5 (FR5) and progressive-ratio schedules of reinforcement. Furthermore, the effects of BHF177 and CGP44532 on nicotine-induced enhancement of brain reward function were evaluated. The results indicated that administration of CGP7930 decreased nicotine self-administration under an FR5 schedule. Administration of either GS39783 or CGP44532 selectively decreased nicotine self-administration, while co-administration of these compounds had additive effects. BHF177 administration selectively decreased nicotine-, but not food-, maintained responding under FR5 and progressive-ratio schedules. The nicotine-induced enhancement of brain reward function was blocked by BHF177 or CGP44532, although the highest doses of both compounds, particularly CGP44532, decreased brain reward function when administered alone, suggesting an additive, rather than interactive, effect. Overall, the present results indicate that GABAB receptor positive modulators, similarly to GABAB receptor agonists, attenuated the reinforcing and reward

  13. Testosterone Administration Reduces Lying in Men

    NARCIS (Netherlands)

    Wibral, M.; Dohmen, T.J.; Klingmüller, Dietrich; Weber, Bernd; Falk, Armin

    2012-01-01

    Lying is a pervasive phenomenon with important social and economic implications. However, despite substantial interest in the prevalence and determinants of lying, little is known about its biological foundations. Here we study a potential hormonal influence, focusing on the steroid hormone

  14. The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy.

    Science.gov (United States)

    Tryniszewski, Wieslaw; Kamiński, Grzegorz; Maziarz, Zbigniew; Nowak, Michal; Gadzicki, Mariusz; Radek, Maciej

    2018-01-10

    Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p Metabolism). We observed

  15. Effects of three different testosterone formulations in female-to-male transsexual persons.

    Science.gov (United States)

    Pelusi, Carla; Costantino, Antonietta; Martelli, Valentina; Lambertini, Martina; Bazzocchi, Alberto; Ponti, Federico; Battista, Giuseppe; Venturoli, Stefano; Meriggiola, Maria C

    2014-12-01

    Gender dysphoria is characterized by a strong discomfort with the gender assigned at birth and the urge to live as a member of the opposite gender. The acquisition of phenotypic features of the desired gender requires the use of cross-sex hormones. Female-to-male (FtM) transsexual persons are treated with testosterone to induce virilization. The aim of the study was to assess the effects of three different testosterone formulations on body weight and composition and metabolic and bone parameters. Forty-five FtM transsexuals were randomly assigned to receive testoviron depot (i.m.: 100 mg/10 days; n = 15), testosterone gel (50 mg/die; n = 15), and testosterone undecanoate (i.m.: 1,000 mg every 6 weeks for the first 6 weeks and then every 12 weeks, n = 15). FtM individuals were studied before, at week 30, and at week 54 of testosterone treatment. Anthropometric, metabolic, bone, hematological, and biochemical parameters were evaluated at baseline and after 12 months of treatment. Lean body mass significantly increased and fat mass decreased in all groups. No modifications were reported in fasting insulin and insulin sensitivity index. High-density plasma lipoprotein levels declined significantly and low-density lipoprotein concentrations increased significantly in the three groups. The activated partial thromboplastin time and factor I did not change while prothrombin time significantly increased in all groups. At week 54, all subjects were amenorrheic and time to amenorrhea did not differ between the three groups. Current general life satisfaction was increased in all subjects after 1 year of treatment. One-year testosterone administration in FtM transsexuals appears to be very safe with no differences among the testosterone formulations used. Our study is preliminary, and the detection of subtle or long-term differences in the effects of the three formulations may require further larger and longer term studies in this and other populations.

  16. Positive modulation of GABA(B) receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats.

    Science.gov (United States)

    Paterson, Neil E; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-07-01

    Acute administration of gamma-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABA(B) receptor-positive modulators may represent potentially improved therapeutic compounds because of their fewer side effects than receptor agonists. The present study investigated the effects of administration of the GABA(B) receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) and coadministration of the GABA(B) receptor-positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) with the GABA(B) receptor agonist (3-amino-2[S]-hydroxypropyl)-methylphosphinic acid (CGP44532) on nicotine- and food-maintained responding under fixed ratio (FR) 5 and progressive ratio schedules of reinforcement. Furthermore, the effects of BHF177 and CGP44532 on nicotine-induced enhancement of brain reward function were evaluated. The results indicated that administration of CGP7930 decreased nicotine self-administration under an FR5 schedule. Administration of either GS39783 or CGP44532 selectively decreased nicotine self-administration, whereas coadministration of these compounds had additive effects. BHF177 administration selectively decreased nicotine- but not food-maintained responding under FR5 and progressive ratio schedules. The nicotine-induced enhancement of brain reward function was blocked by BHF177 or CGP44532, although the highest doses of both compounds, particularly CGP44532, decreased brain reward function when administered alone, suggesting an additive, rather than interactive, effect. Overall, the present results indicate that GABA(B) receptor-positive modulators, similarly to GABA(B) receptor agonists, attenuated the reinforcing and reward

  17. Prenatal testosterone and stuttering.

    Science.gov (United States)

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Parental care, loss of paternity and circulating levels of testosterone and corticosterone in a socially monogamous song bird

    OpenAIRE

    Villavicencio, Camila P; Apfelbeck, Beate; Goymann, Wolfgang

    2014-01-01

    Introduction:\\ud In biparental birds testosterone levels of males are typically high during the mating phase and decrease during the parental phase. Testosterone implants may enhance mating behaviors, increase the likelihood of males to engage in extra-pair mating behavior and may reduce paternal care. Thus, sex steroids such as testosterone influence reproductive behaviors. Little is known, however, as to whether the more subtle differences in physiological concentrations of testosterone tha...

  19. Perioperative synbiotics administration decreases postoperative infections in patients with colorectal cancer: a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    ALINE TABORDA FLESCH

    Full Text Available ABSTRACT Objective: to evaluate the effect of perioperative administration of symbiotics on the incidence of surgical wound infection in patients undergoing surgery for colorectal cancer. Methods: We conducted a randomized clinical trial with colorectal cancer patients undergoing elective surgery, randomly assigned to receive symbiotics or placebo for five days prior to the surgical procedure and for 14 days after surgery. We studied 91 patients, 49 in the symbiotics group (Lactobacillus acidophilus 108 to 109 CFU, Lactobacillus rhamnosus 108 to 109 CFU, Lactobacillus casei 108 to 109 CFU, Bifi dobacterium 108 to 109 CFU and fructo-oligosaccharide (FOS 6g and 42 in the placebo group. Results: surgical site infection occurred in one (2% patient in the symbiotics group and in nine (21.4% patients in the control group (p=0.002. There were three cases of intraabdominal abscess and four cases of pneumonia in the control group, whereas we observed no infections in patients receiving symbiotics (p=0.001. Conclusion: the perioperative administration of symbiotics significantly reduced postoperative infection rates in patients with colorectal cancer. Additional studies are needed to confirm the role of symbiotics in the surgical treatment of colorectal cancer.

  20. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Hajizadeh

    2014-03-01

    Full Text Available Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde in the testis of control, untreated and MAE-treated (1 g/day/kg diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR and P450 cholesterol side-chain cleavage enzyme (P450scc, by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. Please cite this article as: Hajizadeh MR, Eftekhar E, Zal F, Jaffarian A, Mostafavi-Pour Z. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in

  1. Men's health, low testosterone, and diabetes: individualized treatment and a multidisciplinary approach.

    Science.gov (United States)

    Rice, Donna; Brannigan, Robert E; Campbell, R Keith; Fine, Shari; Jack, Leonard; Nelson, Joseph B; Regan-Klich, Janet

    2008-01-01

    Testosterone plays a critical role in male reproductive and metabolic functioning. Serum testosterone levels decrease with age, and low testosterone is associated with a variety of comorbidities, including insulin resistance, type 2 diabetes, obesity, metabolic syndrome, and cardiovascular disease. Men with type 2 diabetes have been shown to have significantly lower testosterone levels than men without diabetes. Several forms of testosterone replacement therapy (eg, oral, injectable, buccal, transdermal preparations) are available for use in the United States. The primary goals of testosterone therapy are to restore physiologic testosterone levels and reduce the symptoms of hypogonadism. Testosterone therapy may be a viable option in some men with diabetes and low testosterone; however, clinicians must be aware of contraindications to therapy (eg, prostate cancer and male breast cancer), implement appropriate monitoring procedures, and ensure that patient expectations are realistic regarding treatment outcome. Data suggest that testosterone therapy may have a positive effect on bones, muscles, erythropoiesis and anemia, libido, mood and cognition, penile erection, cholesterol, fasting blood glucose, glycated hemoglobin, insulin resistance, visceral adiposity, and quality of life. Sexual health may be a window into men's health; thus, more effective communication strategies are needed between clinicians and men with diabetes to ensure that sexual health topics are adequately addressed. Diabetes educators can play a key role in screening for low testosterone, providing relevant information to patients, and increasing clinician awareness of the need to address men's sexual health and implement appropriate strategies. Multidisciplinary care and individualized treatment are needed to optimize outcome.

  2. "Low Testosterone Levels in Body Fluids Are Associated With Chronic Periodontitis".

    Science.gov (United States)

    Kellesarian, Sergio Varela; Malmstrom, Hans; Abduljabbar, Tariq; Vohra, Fahim; Kellesarian, Tammy Varela; Javed, Fawad; Romanos, Georgios E

    2017-03-01

    There is a debate over the association between low testosterone levels in body fluids and the occurrence of chronic periodontitis (CP). The aim of the present systematic review was to assess whether low testosterone levels in body fluids reflect CP. In order to identify studies relevant to the focus question: "Is there a relationship between low testosterone levels in body fluids and CP?" an electronic search without time or language restrictions was conducted up to June 2016 in indexed databases using different keywords: periodontitis, chronic periodontitis, periodontal diseases, testosterone, and gonadal steroid hormones. A total of eight studies were included in the present systematic review. The number of study participants ranged from 24 to 1,838 male individuals with ages ranging from 15 to 95 years. Seven studies measured testosterone levels in serum, two studies in saliva, and one study in gingiva. Four studies reported a negative association between serum testosterone levels and CP. Two studies reported a positive association between decreased testosterone levels in serum and CP. Increased levels of salivary testosterone among patients with CP were reported in one study; whereas one study reported no significant difference in the concentration of salivary testosterone between patients with and without CP. One study identified significant increase in the metabolism of testosterone in the gingiva of patients with CP. Within the limits of the evidence available, the relationship between low testosterone levels and CP remains debatable and further longitudinal studies and control trials are needed.

  3. Testosterone treatment in the aging male: myth or reality?

    Science.gov (United States)

    Nigro, Nicole; Christ-Crain, Mirjam

    2012-03-19

    The definition of late onset hypogonadism in the aging male is controversially debated, and according to the latest literature consists of at least three especially sexual symptoms such as loss of morning erection, low sexual desire and erectile dysfunction as well as a total testosterone <8-11 nmol/l. Testosterone replacement therapy in the aging male has been shown to have a beneficial effect on muscle and fat mass as well as on bone mineral density, with more conflicting effects observed on muscle strength, sexual function, mood and quality of life. The prescriptions for testosterone products for the aging male increased by over 170% in the previous five years. Furthermore, there is a lot of epidemiological data showing an inverse relationship between testosterone levels and obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. However, only few small randomised placebo-controlled studies have investigated the effect of testosterone replacement therapy on insulin resistance and HbA1c levels, with controversial results. Importantly, so far the long-term safety and efficacy of testosterone replacement therapy has not been established. Although until now no clear evidence has been found that testosterone replacement therapy has a causative role in prostate cancer or indeed in changes of the biology of the prostate, in a recent meta-analysis a 4-fold increased risk of prostate-associated event rates in testosterone treated elderly men sounds a note of caution. Also the risk for cardiovascular events is still not clear and caution is warranted especially in elderly men with cardiovascular disease and limited mobility. In summary, the actual available evidence of long-term risks and outcome of testosterone replacement therapy is still very limited and carefully designed placebo-controlled trials of testosterone administration to assess the risks and benefits of such a therapy are required. Until then, testosterone treatment in elderly men

  4. Testosterone supplementation restores vasopressin innervation in the senescent rat brain

    NARCIS (Netherlands)

    Goudsmit, E.; Fliers, E.; Swaab, D. F.

    1988-01-01

    The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

  5. Air Ambulance Delivery and Administration of Four-factor Prothrombin Complex Concentrate Is Feasible and Decreases Time to Anticoagulation Reversal.

    Science.gov (United States)

    Vines, Claire; Tesseneer, Stephanie J; Cox, Robert D; Darsey, Damon A; Carbrey, Kristin; Puskarich, Michael A

    2017-10-27

    The objective was to evaluate the feasibility, safety, and preliminary efficacy of four-factor prothrombin complex concentrate (4-factor PCC) administration by an air ambulance service prior to or during transfer of patients with warfarin-associated major hemorrhage to a tertiary care center for definitive management (interventional arm) compared to patients receiving 4-factor PCC following transfer by air ambulance or ground without 4-factor PCC treatment (conventional arm). This was a retrospective chart review of patients presenting to a large academic medical center. All patients presenting to the emergency department (ED) treated with 4-factor PCC from April 1, 2014, through June 30, 2016, were identified. For this study, only transfer patients with an International Normalized Ratio (INR) > 1.5 actively treated with warfarin were included. The primary outcome was the proportion of patients with an INR ≤ 1.5 upon tertiary care hospital arrival, and the secondary efficacy outcome was difference in time to achievement of INR ≤ 1.5. Additional safety and efficacy objectives included difference in thromboembolic complications, length of stay, intensive care unit length of stay, and inpatient mortality between groups. Of the 72 included patients, a higher proportion of patients in the interventional group had an INR ≤ 1.5 on ED arrival (proportion difference = 0.82, 95% confidence interval = 0.64-0.92, p < 0.0001) and significantly reduced time to observed INR ≤ 1.5 (181 minutes vs. 541 minutes, p = 0.001). No differences were observed in thromboembolic complications or patient-centered outcomes with the exception of mortality, which was significantly higher in patients in the interventional group. This group was also observed to have lower Glasgow Coma Scale score and higher intubation rates prior to transfer and treatment. Dispatch of an air ambulance carrying 4-factor PCC with administration prior to transfer is feasible and leads to more rapid

  6. Testosterone Replacement Therapy and Mortality in Older Men.

    Science.gov (United States)

    Hackett, G I

    2016-02-01

    While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Several authors blame advertising and the availability of more convenient formulations, whilst others have pointed out that the routine testing of men with erectile dysfunction (ED) (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous under-diagnosis and under-treatment in line with evidence based guidelines. It is unlikely that persuasive advertising or convenient formulations could grow a market over such a sustained period if the treatment was not effective. Urologists and primary care physicians are the most frequent initiators of TRT usually for ED. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with a possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing that therapy associated with clear increases in serum testosterone levels to the normal range is associated with reduced all-cause mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively, they have compared non-treated patients with under-treated or non-compliant subjects involving a range of different therapy regimes. Recent evidence suggests long-acting injections may be associated with decreased cardiovascular risk, but the

  7. Decreasing half-life of dieldrin in egg yolk following a single oral administration of aldrin to laying hens.

    Science.gov (United States)

    Furusawa, N

    2001-01-01

    Laying hens were treated orally with a single dose of aldrin (AD) 1 mg/kg body weight. Concentrations (microgram/g) of AD or its epoxide (= dieldrin, DD) in the yolk of eggs laid for 21 days after AD treatment were determined by normal-phase high-performance liquid chromatography. The limits of determination were 0.02 microgram/g for AD and 0.03 microgram/g for DD, respectively. After AD treatment, although the low levels of AD (mean 0.02-0.03 microgram/g) were observed only during a three-day period (from 4th to 6th days), DD (mean 0.15 microgram/g) was found already on the 2nd day, indicating that the epoxidation of AD to DD in the hen's body is rapid. The highest level of DD (mean 0.40 microgram/g) was detected on the 6th day, and then DD levels decreased slowly and were detected up to the 21st day. In this decreasing phase, the half-life of DD in the yolk was estimated to be 25.6 days with a 95% confidence interval from 22.7 to 29.4 days.

  8. Intracerebroventricular administration of conjugated linoleic acid (CLA) inhibits food intake by decreasing gene expression of NPY and AgRP.

    Science.gov (United States)

    Cao, Zi-Peng; Wang, Feng; Xiang, Xue-Song; Cao, Rui; Zhang, Wen-Bin; Gao, Shuang-Bin

    2007-05-18

    Dietary conjugated linoleic acid (CLA) has been investigated for its beneficial effects on disease prevention and treatment, and now obesity is one of the most perspective researching highlights. In a variety of experimental models, the results of studies on the effects of CLA on food intakes are somewhat inconsistent. Our experiment was conducted to extend these observations to hypothalamus and other regions within the central nervous system so that the mechanism of the actions of CLA might be more easily elucidated. In the experiment, a permanent cannula was inserted into the lateral ventricle of each rat. For the experiment, animals received intracerebroventricular injections of either 150nmol (n=16) CLA, or LA as non-conjugated control, or normal saline as vehicle. Hypothalamus and blood samples were collected at the 2nd, 4th, 8th, and 14th day. The results show that CLA in cerebral ventricle can inhibit food intake of experimented rats and this inhibition is related with the decreased expression of neuropeptides Y (NPY) and agouti-related protein (AgRP). The circulating leptin level was also increased by this tentative treatment (2.94+/-0.71 versus 1.18+/-0.18ng/ml). However, the glucose metabolism was not affected by ICV CLA. It is concluded that CLA in brain can inhibit the appetite of rats through the mechanism of decreasing the expression of NPY and AgRP.

  9. Progressive Improvement of T-Scores in Men with Osteoporosis and Subnormal Serum Testosterone Levels upon Treatment with Testosterone over Six Years

    Directory of Open Access Journals (Sweden)

    Ahmad Haider

    2014-01-01

    Full Text Available Testosterone deficiency leads to bone loss and testosterone treatment has a beneficial effect. This study investigated the effects of normalizing serum testosterone on bone mineral density in 45 men with osteoporosis, diagnosed with testosterone deficiency (serum testosterone levels <12.1 nmol/L, T-scores: (mean ± SD −3.12 ± 0.45, minimum: −4.10, and maximum: −2.60. In a cumulative, prospective, registry study of hypogonadal men (mean age: 53 ± 7 years they received parenteral testosterone undecanoate of 1000 mg/12 weeks for up to six years. After one year 44 men were included in the registry, after two years 36 men, after three years 32 men, after four years 25 men, after five years 10 men and after six years 4 men. The declining numbers do not reflect drop-out rates but are a result of the registry design. Over the 6 year period there was a significant and progressive improvement of the T-scores in these men. Normalizing of serum testosterone leads to an improvement of bone mineral density and this improvement was progressive with the time period of testosterone administration. In this study of 6-years many men with testosterone deficiency suffered from classical diagnoses (Klinefelter’s syndrome and testicular pathology hitherto undiagnosed.

  10. Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients.

    Science.gov (United States)

    Weickhardt, Andrew J; Doebele, Robert C; Purcell, W Thomas; Bunn, Paul A; Oton, Ana B; Rothman, Micol S; Wierman, Margaret E; Mok, Tony; Popat, Sanjay; Bauman, Julie; Nieva, Jorge; Novello, Silvia; Ou, Sai-Hong Ignatius; Camidge, D Ross

    2013-07-01

    Crizotinib is a tyrosine kinase inhibitor active against ALK, MET, and ROS1. We previously reported that crizotinib decreases testosterone in male patients. The detailed etiology of the effect, its symptomatic significance, and the effectiveness of subsequent testosterone replacement have not been previously reported. Male cancer patients treated with crizotinib had total testosterone levels measured and results compared with non-crizotinib-treated patients. Albumin, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and/or luteinizing hormone (LH) were tracked longitudinally. A subset of patients had free testosterone levels measured and a hypogonadal screening questionnaire administered. Patients receiving subsequent testosterone supplementation were assessed for symptomatic improvement. Mean total testosterone levels were -25% below the lower limit of normal (LLN) in 32 crizotinib-treated patients (27 of 32 patients below LLN, 84%) compared with +29% above LLN in 19 non-crizotinib-treated patients (6 of 19 below LLN, 32%), P = .0012. Levels of albumin and SHBG (which both bind testosterone) declined rapidly with crizotinib, but so did FSH, LH, and free testosterone, suggesting a centrally mediated, true hypogonadal effect. Mean free testosterone levels were -17% below LLN (19 of 25 patients below LLN, 76%). Eighty-four percent (16 of 19) with low free levels, and 79% (19/24) with low total levels had symptoms of androgen deficiency. Five of 9 patients (55%) with low testosterone given testosterone supplementation had improvement in symptoms, coincident with increases in testosterone above LLN. Symptoms of androgen deficiency and free or total/free testosterone levels should be tracked in male patients on crizotinib with consideration of testosterone replacement as appropriate. Copyright © 2013 American Cancer Society.

  11. Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques

    Directory of Open Access Journals (Sweden)

    Koterski James

    2006-03-01

    Full Text Available Abstract Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  12. The Effects of Trifluralin on LH, FSH and Testosterone Hormone Levels and Testis Histological Changes in Adult Rats

    Directory of Open Access Journals (Sweden)

    Mehrdad Shariati

    2008-01-01

    Full Text Available Background: Trifluralin is a herbicide and used in agriculture widely. It enters plants throughdeveloping roots and stops plant cells from division and elongation (meristemic inhibitor.Extensive application of trifluralin to control annual grasses and broadleaf weeds in agriculture,horticulture and horn garden, leads to environmental pollution and its entrance into the food chaincould have determined effects on human and other species. In this research the effects of trifluralinon reproductive parameters of the male rats including serum luteinizing hormone (LH, folliclestimulatinghormone (FSH, testosterone levels, and changes in testicular tissue and body weightwere investigated.Materials and Methods: For this purpose male rats were randomly divided in 5 groups, to includecontrol, sham (received normal saline as a solvent, and three experimental groups which received500, 1000 and 2000 mg/kg oral trifluralin respectively. After 16 days, body and testis weight weremeasured and blood samples were taken from heart and used for measurement of LH, FSH andtestosterone levels. To evaluate histological changes, testes were removed and weighed and, afterobtaining tissue section, stained by HE.Results: Serum testosterone, FSH, and LH levels showed significant decrease in experimentalgroups (p<0.05. There was significant decrease in the number of germinal and somatic cells intestis in experimental groups. There was also a significant decrease in body and testis weight inexperimental groups.Conclusion: It can be concluded that oral administration of trifluralin could decrease gonadotropinsand testosterone hormone levels and also this herbicide could have hazardous effects on testistissue.

  13. Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

    Science.gov (United States)

    Kasahara, Masataka; Ichinohe, Tatsuya; Okamoto, Sota; Okada, Reina; Kanbe, Hiroaki; Matsuura, Nobuyuki

    2015-06-01

    To determine whether continuous administration of nitrous oxide and remifentanil—either alone or together—alters blood flow in oral tissues during sevoflurane anesthesia. Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 μg/kg/min remifentanil, and their combination) for 20 min. Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

  14. Long-term administration of ketamine induces erectile dysfunction by decreasing neuronal nitric oxide synthase on cavernous nerve and increasing corporal smooth muscle cell apoptosis in rats.

    Science.gov (United States)

    Shang, Hung-Sheng; Wu, Yi-No; Liao, Chun-Hou; Chiueh, Tzong-Shi; Lin, Yuh-Feng; Chiang, Han-Sun

    2017-09-26

    We investigated and evaluated the mechanisms of erectile dysfunction (ED) in a rat model of long-term ketamine administration. Adult male Sprague-Dawley rats (n = 32) were divided into four groups: namely the control group receiving intraperitoneal injection of saline, 1-month, 2-month and 3-month groups receiving daily intraperitoneal injection of ketamine (100 mg/kg/day) for 1, 2, and 3 month respectively. After treatment, animals underwent an erectile response protocol to assess intracavernosal pressure (ICP). Smooth muscle content was evaluated. Neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression were assessed using immunostaining assay. Ketamine-induced apoptosis was analyzed using TUNEL assay. Long-term ketamine administration caused significantly decreased erectile responses as measured by ICP. Smooth muscle content was significantly decreased in the ketamine-treated rats for 3 months. In the erectile tissue, ketamine administration significantly reduced nNOS expression and increased iNOS content compared with controls, whereas eNOS expression was not altered. Ketamine induced apoptosis in corpus cavernosum. The present study demonstrates that long-term ketamine administration led to erectile dysfunction in rat. The molecular mechanisms of ketamine-induced ED involved the increased apoptosis and up-regulated iNOS expression incorporating with loss of corporal smooth muscle content and reduced nNOS expression in cavernous nerve.

  15. Testosterone prevents protein loss via the hepatic urea cycle in human.

    Science.gov (United States)

    Lam, Teresa; Poljak, Anne; McLean, Mark; Bahl, Neha; Ho, Ken K Y; Birzniece, Vita

    2017-04-01

    The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied. To determine whether testosterone reduces hepatic urea production. An open-label study. Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day). The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with 15 N 2 -urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated. Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min; P  Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% ( P  testosterone administration ( r 2  = 0.59, P  Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle. © 2017 European Society of Endocrinology.

  16. Exposure to urban stressors and free testosterone plasma values.

    Science.gov (United States)

    Sancini, Angela; Tomei, Francesco; Tomei, Gianfranco; Ciarrocca, Manuela; Palermo, Paola; Gioffrè, Pier Agostino; Tasciotti, Zaira; Fiaschetti, Maria; Cetica, Carlotta; Caciari, Tiziana

    2011-08-01

    The chemical agents present in the environment, such as traffic pollutants, may affect male fertility. Traffic policemen are daily exposed to traffic pollutants. The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in free testosterone plasma values in male traffic policemen versus administrative staff of Municipal Police of a big Italian city. Both groups were divided into two subgroups based on age (first group: 30-40 years; second group: 41-50 years) to assess whether age could affect laboratory results of free testosterone plasma levels in traffic policemen versus controls. The characterization of exposure to urban pollutants for traffic policemen was assessed using the concentrations of pollutants monitored in fixed stations. A total of 220 subjects were studied: 110 traffic policemen and 110 controls, after excluding subjects with main confounding factors. Mean free testosterone values were significantly lower in traffic policemen than in controls (P testosterone values for classes of age (30-40 and 41-50 year) of workers (respectively P testosterone values in traffic policemen and in controls was significant (P free testosterone plasma levels could be used as an early biological marker, to be employed in occupational sets, valuable for the group, even before the onset of values out of range and of fertility disorders.

  17. Exogenous Testosterone Stimulates Gluconeogenesis In ...

    African Journals Online (AJOL)

    ... source of energy for the mammalian brain. The mechanism of action of steroid hormones on target organ cells, and the role of testosterone as a performance enhancing drug are discussed. Keywords: Exogenous testosterone, Protein, Glucose, Gluconeogenesis, Hypoproteinemic rat. Animal Research International Vol.

  18. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    Science.gov (United States)

    Musicki, Biljana; Zhang, Yuxi; Chen, Haolin; Brown, Terry R; Zirkin, Barry R; Burnett, Arthur L

    2015-01-01

    Testosterone deficiency is associated with sickle cell disease (SCD), but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle) exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH) levels compared with wild type (WT) mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol)- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR), but not cholesterol side-chain cleavage enzyme (P450scc), in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi) exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  19. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    Directory of Open Access Journals (Sweden)

    Biljana Musicki

    Full Text Available Testosterone deficiency is associated with sickle cell disease (SCD, but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH levels compared with wild type (WT mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR, but not cholesterol side-chain cleavage enzyme (P450scc, in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  20. Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces

    OpenAIRE

    Holtfrerich, Sarah K. C.; Schwarz, Katharina A.; Sprenger, Christian; Reimers, Luise; Diekhof, Esther K.

    2016-01-01

    Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on att...

  1. Suppression of endogenous testosterone production attenuates the response to strength training

    DEFF Research Database (Denmark)

    Kvorning, Thue; Andersen, Marianne; Brixen, Kim

    2006-01-01

    We hypothesized that suppression of endogenous testosterone would inhibit the adaptations to strength training in otherwise healthy men. Twenty-two young men with minor experience with strength training participated in this randomized, placebo-controlled, double-blinded intervention study......-repetition maximum (RM) loads, 3/wk]. A strength test, blood sampling, and whole body DEXA scan were performed at weeks 4 and 12. Endogenous testosterone decreased significantly (P ... that endogenous testosterone is of paramount importance to the adaptation to strength training....

  2. Consistent individual variation in day, night, and GnRH-induced testosterone concentrations in house sparrows (Passer domesticus).

    Science.gov (United States)

    Needham, Katie B; Dochtermann, Ned A; Greives, Timothy J

    2017-05-15

    The hypothalamic-pituitary-gonadal (HPG) axis, with gonadotropin-releasing hormone (GnRH) initiating the endocrine cascade, regulates testosterone secretion. Testosterone, through its pleiotropic effects, plays a crucial role in coordinating morphology, physiology and behavior in a reproductive context. The concentration of circulating testosterone, however, varies over the course of the day and in response to other internal or external stimuli, potentially making it difficult to relate testosterone sampled at one time point with traits of interest. Many researchers now utilize the administration of exogenous GnRH to elicit a standardized stimulation of testosterone secretion. However, it has remained unclear if and how this exogenously stimulated activation of the HPG axis is related with endogenously regulated testosterone that is capable of influencing testosterone related traits. Repeated measures of a hormone can uncover consistent individual variation in hormonal differences at the HPG axis level, variation that potentially stems from underlying genetic variation in a population experiencing identical environmental cues. Thus, we asked, using the house sparrow (Passer domesticus), how daily endogenous variation in testosterone profiles relates to GnRH-induced testosterone secretion. Further, we explore the relationship between endogenous daily testosterone peaks and GnRH-induced testosterone with badge size, a morphological trait related with status within a social group. We found that GnRH-induced testosterone levels reflect a highly repeatable hormonal phenotype that is strongly correlated with nighttime testosterone levels. The results demonstrate the usefulness of GnRH-induced testosterone in studies aimed at understanding individual variation and selection on endogenously regulated testosterone levels and the potential importance of nighttime testosterone levels to physiology and behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Use of Exogenous Testosterone for the Treatment of Male Factor Infertility: A Survey of Nigerian Doctors.

    Science.gov (United States)

    Omisanjo, Olufunmilade Akinfolarin; Ikuerowo, Stephen Odunayo; Abdulsalam, Moruf Adekunle; Ajenifuja, Sheriff Olabode; Shittu, Khadijah Adebisi

    2017-01-01

    Though exogenous testosterone is known for its contraceptive effects in men, it is sometimes prescribed by medical practitioners for the treatment of male factor infertility in the mistaken belief that exogenous testosterone improves sperm count. The aim of this study was to evaluate the scope of testosterone use in the treatment of male factor infertility by medical practitioners in Lagos, Nigeria. A survey using a structured questionnaire was carried out amongst doctors attending a regular Continuing Medical Education (CME) programme in Lagos, Nigeria. There were 225 respondents. Most of the respondents (69.8%, n = 157) indicated that exogenous testosterone increases sperm count. Only 22 respondents (9.8%) indicated (correctly) that exogenous testosterone decreases sperm count. Seventy-seven respondents (34.2%) had prescribed some form of exogenous testosterone in the treatment of male factor infertility. The vast majority of respondents who had prescribed testosterone (81.8%, n = 63) thought exogenous testosterone increases sperm count. There was no statistically significant difference in the pattern of prescription across the respondents' specialty (p = 0.859) or practice type (p = 0.747). The misuse of exogenous testosterone for the treatment of male infertility was common amongst the respondents, with most of them wrongly believing that exogenous testosterone increases sperm count.

  4. Medication calculation and administration workshop and hurdle assessment increases student awareness towards the importance of safe practices to decrease medication errors in the future.

    Science.gov (United States)

    Wallace, Darlene; Woolley, Torres; Martin, David; Rasalam, Roy; Bellei, Maria

    2016-01-01

    Medication errors are the second most frequently reported hospital incident in Australia and are a global concern. A "Medication Calculation and Administration" workshop followed by a "hurdle" assessment (compulsory task mandating a minimum level of performance as a condition of passing the course) was introduced into Year 2 of the James Cook University medical curriculum to decrease dosage calculation and administration errors among graduates. This study evaluates the effectiveness of this educational activity as a long-term strategy to teach medical students' essential skills in calculating and administering medications. This longitudinal study used a pre- and post-test design to determine whether medical students retained their calculation and administration skills over a period of 4 years. The ability to apply basic mathematical skills to medication dose calculation, principles of safe administration (Part 1), and ability to access reference materials to check indications, contraindications, and writing the medication order with correct abbreviations (Part 2) were compared between Year 2 and 6 assessments. Scores for Parts 1, 2 and total scores were nearly identical from Year 2 to Year 6 (P = 0.663, 0.408, and 0.472, respectively), indicating minimal loss of knowledge by students in this period. Most Year 6 students (86%) were able to recall at least 5 of the "6 Rights of Medication Administration" while 84% reported accessing reference material and 91% reported checking their medical calculations. The "Medication Calculation and Administration" workshop with a combined formative and summative assessment - a "hurdle" - promotes long-term retention of essential clinical skills for medical students. These skills and an awareness of the problem are strategies to assist medical graduates in preventing future medication-related adverse events.

  5. Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes.

    Science.gov (United States)

    Mitsuhashi, Kazuteru; Senmaru, Takafumi; Fukuda, Takuya; Yamazaki, Masahiro; Shinomiya, Katsuhiko; Ueno, Morio; Kinoshita, Shigeru; Kitawaki, Jo; Katsuyama, Masato; Tsujikawa, Muneo; Obayashi, Hiroshi; Nakamura, Naoto; Fukui, Michiaki

    2016-01-01

    Decreases in serum testosterone concentrations in aging men are associated with metabolic disorders. Testosterone has been reported to increase GLUT4-dependent glucose uptake in skeletal muscle cells and cardiomyocytes. However, studies on glucose uptake occurring in response to testosterone stimulation in adipocytes are currently not available. This study was designed to determine the effects of testosterone on glucose uptake in adipocytes. Glucose uptake was assessed with 2-[(3)H] deoxyglucose in 3T3-L1 adipocytes. GLUT4 translocation was evaluated in plasma membrane (PM) sheets and PM fractions by immunofluorescence and immunoblotting, respectively. Activation of GLUT4 translocation-related protein kinases, including Akt, AMPK, LKB1, CaMKI, CaMKII, and Cbl was followed by immunoblotting. Expression levels of androgen receptor (AR) mRNA and AR translocation to the PM were assessed by real-time RT-PCR and immunoblotting, respectively. The results showed that both high-dose (100 nM) testosterone and testosterone-BSA increased glucose uptake and GLUT4 translocation to the PM, independently of the intracellular AR. Testosterone and testosterone-BSA stimulated the phosphorylation of AMPK, LKB1, and CaMKII. The knockdown of LKB1 by siRNA attenuated testosterone- and testosterone-BSA-stimulated AMPK phosphorylation and glucose uptake. These results indicate that high-dose testosterone and testosterone-BSA increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes by inducing the LKB1/AMPK signaling pathway.

  6. Testosterone replacement, cardiovascular system and risk factors in the aging male.

    Science.gov (United States)

    Vigna, G B; Bergami, E

    2005-01-01

    Investigations concerning the role of testosterone replacement on cardiovascular risk show conflicting results. Treatments with supraphysiological doses seem detrimental in animal models and men. On the other hand, cross-sectional, prospective and angiographic studies frequently find an inverse, favorable relationship between plasma testosterone and cardiovascular events. Testosterone replacement therapy in the hypogonadic elderly has a positive or at least neutral effect on several coronary disease risk factors. Testosterone appears to decrease LDL-cholesterol without adversely affecting HDL cholesterol, and improve insulin sensibility and the thrombotic/fibrinolytic balance; testosterone does not negatively influence the inflammatory response and arterial wall vasoreactivity. These findings provide a measure of reassurance concerning potential adverse heart effects of testosterone substitutional therapy in older men, even if more specific trials than reported are needed to overcome residual suspicions.

  7. Free testosterone and free dihydrotestosterone throughout the life span of men.

    Science.gov (United States)

    Stárka, Luboslav; Pospísilová, Hana; Hill, Martin

    2009-08-01

    The dihydrotestosterone/testosterone ratio seems to be an important factor in the expression of androgenic activity, especially in the prostate and pilosebaceous unit. Whereas the decline of testosterone in aging men is well known, controversial data can be found concerning the age dependence of dihydrotestosterone levels. Hormonal values from our database served for the construction of the life span curve of free dihydrotestosterone/free testosterone ratio. The results of testosterone, dihydrotestosterone and SHBG determination obtained by immunoassays from 13,152 male patients were used for the calculation of free steroid content and the construction of the age dependence curves. After initial high free dihydrotestosterone: free testosterone ratio in infancy it decreases at the start of puberty and remains practically without change from approx. 20 years of age till senescence. The course of free dihydrotestosterone/free testosterone ratio demonstrates the role of dihydrotestosterone for androgen functions especially in prepubertal age.

  8. Lack of melatonin action on testosterone production by superfused rat interstitial cells.

    Science.gov (United States)

    Jarrige, J F; Thieblot, P; Boucher, D

    1984-09-01

    The direct effect of increasing doses of melatonin (10(-8) to 10(-5) M) on testosterone production by superfused rat interstitial cells was studied. A constant basal testosterone output was observed for approximately 3 h after the initial high release. A continuous hypothalamo-pituitary stimulation induced a rapid testosterone response reaching peak values in 40-60 min, then decreasing progressively. Basal testosterone release was not modified by 20 or 140 min melatonin infusions. Furthermore, melatonin induced no alteration of the stimulative testosterone response when directly infusing the cells. This study demonstrates that melatonin in vitro has no direct effect on testosterone production by adult rat interstitial cells. It would seem, therefore, that the well known inhibitory influence of melatonin on rat reproductive function is not produced by a direct effect on Leydig cells.

  9. 21 CFR 556.710 - Testosterone propionate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  10. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    Directory of Open Access Journals (Sweden)

    Johanna Abrigo

    2016-01-01

    Full Text Available Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.

  11. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    Science.gov (United States)

    Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando

    2016-01-01

    Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes. PMID:27579157

  12. Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model

    Science.gov (United States)

    Nahata, M; Saegusa, Y; Sadakane, C; Yamada, C; Nakagawa, K; Okubo, N; Ohnishi, S; Hattori, T; Sakamoto, N; Takeda, H

    2014-01-01

    Background Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice. Methods Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress. Key Results Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist. Conclusions & Inferences Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress. PMID:24684160

  13. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer.

    Science.gov (United States)

    Pompe, Raisa S; Karakiewicz, Pierre I; Zaffuto, Emanuele; Smith, Ariane; Bandini, Marco; Marchioni, Michele; Tian, Zhe; Leyh-Bannurah, Sami-Ramzi; Schiffmann, Jonas; Delouya, Guila; Lambert, Carole; Bahary, Jean-Paul; Beauchemin, Marie Claude; Barkati, Maroie; Ménard, Cynthia; Graefen, Markus; Saad, Fred; Tilki, Derya; Taussky, Daniel

    2017-07-01

    Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported. To examine testosterone kinetics in a large series of contemporary patients after EBRT. The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses. Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence. Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence. EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism. We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study

  14. Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice.

    Science.gov (United States)

    Jalili, Cyrus; Salahshoor, Mohammad Reza; Naseri, Ali

    2014-06-01

    Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. In this study, hydro-alcoholic extract of U.dioica was prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56 male mice for 28 consequent days. These mice were randomly assigned to 8 groups (n=7) and sperm parameters (sperm cells viability, count, motility, and morphology), testis and prostate weight, testis histology and testosterone hormone were analyzed and compared. The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperm cells, and testis weight compared to control group (p=0.00). However, increasing the dose of U.dioica significantly boosted motility, count, normal morphology of sperm cells, seminiferous tubules diameter, and testosterone in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg doses in comparison with control group (p=0.00). It seems that U.dioica hydro-alcoholic extract administration could increase the quality of spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters.

  15. Effect of obestatin on morphometry of testes and testosterone ...

    African Journals Online (AJOL)

    This study was designed to evaluate the effects of chronic intra peritoneal administration of obestatin on plasma testosterone concentrations and cellular morphometry of the testes in male Sprague Dawly rats. The treatment groups were injected with obestatin (1 nmol/100 μl saline i.p), while the control groups received ...

  16. Transdermal testosterone replacement therapy in men

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  17. Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

    Science.gov (United States)

    Pongkan, Wanpitak; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2015-01-01

    Background Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R) periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV) function and heart rate variability (HRV), and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX) rats. Methodology ORX or sham-operated male Wistar rats (n = 24) were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered) or the vehicle for 8 weeks. The ejection fraction (EF) and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. Results Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats. Conclusions Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats. PMID:25822979

  18. Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats.

    Science.gov (United States)

    Kataoka, Tomoya; Hotta, Yuji; Maeda, Yasuhiro; Kimura, Kazunori

    2017-12-01

    Testosterone is believed to mediate the penile erectile response by producing adequate nitric oxide; therefore, testosterone deficiency results in erectile dysfunction through decreased nitric oxide bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone deficiency remain unclear. To investigate the mechanism of endothelial dysfunction in a rat model of testosterone deficiency. Rats were distributed into 3 groups: castrated (Cast), castrated and supplemented with testosterone (Cast + T), and sham (Sham). In the Cast + T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats received only the vehicle. Erectile function using intracavernosal pressure and mean arterial pressure measurements after electrical stimulation of the cavernous nerve, endothelial function using isometric tension, asymmetric dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and tandem mass spectrometry, and inflammatory biomarker expression were performed 4 weeks after the operation. In the Cast group, the ratio of intracavernosal pressure to mean arterial pressure significantly decreased, acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and inflammation biomarker levels were significantly increased (P Testosterone injection significantly improved each of these parameters (P testosterone deficiency on erectile function and the effect of testosterone replacement therapy. This study provides evidence of the influence of testosterone deficiency on endothelial function by investigating ADMA and oxidative stress. A major limitation of this study is the lack of a direct link of increased ADMA by oxidative stress to inflammation. Testosterone deficiency increased not only ADMA levels but also oxidative stress and inflammation in castrated rats, which can cause damage to the corpus cavernosum, resulting in erectile dysfunction. Kataoka T, Hotta Y

  19. Testosterone signaling and the regulation of spermatogenesis

    OpenAIRE

    Walker, William H

    2011-01-01

    Spermatogenesis and male fertility are dependent upon the presence of testosterone in the testis. In the absence of testosterone or the androgen receptor, spermatogenesis does not proceed beyond the meiosis stage. The major cellular target and translator of testosterone signals to developing germ cells is the Sertoli cell. In the Sertoli cell, testosterone signals can be translated directly to changes in gene expression (the classical pathway) or testosterone can activate kinases that may reg...

  20. TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

    Directory of Open Access Journals (Sweden)

    Rodrigo NITSCHE

    2014-03-01

    Full Text Available Context Hypogonadism is a common clinical situation in male patients with liver cirrhosis. Objectives The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD score. Methods In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Results Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10 and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD ≤18 - group (A (P<0.05. Conclusions Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD ≤18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation.

  1. A brief history of testosterone.

    Science.gov (United States)

    Freeman, E R; Bloom, D A; McGuire, E J

    2001-02-01

    We explore the history of testosterone in the context of medical and scientific developments. A review of the scientific and historical literature was conducted. The origins and effects of testosterone have been recognized throughout the history of humankind. Hunter performed testicular transplantation experiments in 1767 while studying tissue transplantation techniques, and almost a century later Berthold linked the physiological and behavioral changes of castration to a substance secreted by the testes. Brown-Séquard gave birth to the field of organotherapy in 1889 when he announced that his auto-injection of testicular extracts resulted in rejuvenated physical and mental abilities. Steinach and Niehans expanded upon Brown-Séquard's work with rejuvenation treatments involving vasoligation, tissue grafts and cellular injections. In 1935 David et al isolated the critical ingredient in organotherapeutic treatments, testosterone. The effects of the powerful hormone testosterone continue to inspire research and controversy 65 years later.

  2. Low Testosterone and Men's Health

    Science.gov (United States)

    ... typical male characteristics, such as facial, pubic, and body hair as well as muscle. This hormone also helps ... low testosterone may cause a man to lose body hair, muscle bulk, and strength and to gain body ...

  3. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice.

    Directory of Open Access Journals (Sweden)

    Neira Sáinz

    Full Text Available Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001. This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a (P<0.05, and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx (P<0.05 and muscle RING finger 1 (MuRF1 (P<0.05. Moreover, leptin increased (P<0.01 protein expression levels of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha, a regulator of muscle fiber type, and decreased (P<0.05 myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01 the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA and cyclin D1, and increased (P<0.01 myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation.

  4. Controversies in testosterone supplementation therapy

    Directory of Open Access Journals (Sweden)

    Mohit Khera

    2015-04-01

    Full Text Available Testosterone has now become one of the most widely used medications throughout the world. The rapid growth of the testosterone market in the past 10 years is due to many factors. We currently have a worldwide aging population. In the US, the number of men 65 years old or older is increasing 2-3 times faster than the number of men younger than 65 years. In addition, poor general health and certain medical conditions such as diabetes/metabolic syndrome (MetS, cardiovascular disease (CVD, and osteoporosis have been associated with low serum testosterone levels. [1],[2],[3] There are now fewer concerns regarding the development of prostate cancer (PCa after testosterone therapy, making it a more attractive treatment option. Finally, the introduction of different forms of testosterone supplementation therapy (TST with increased promotion, marketing, and direct-to-consumer advertising is also driving market growth. As the demand for TST continues to grow, it is becoming more important for clinicians to understand how to diagnose and treat patients with low testosterone.

  5. Effects of testosterone and estradiol on anxiety and depressive-like behavior via a non-genomic pathway

    OpenAIRE

    Filova, Barbora; Malinova, Maria; Babickova, Janka; Tothova, Lubomira; Ostatnikova, Daniela; Celec, Peter; Hodosy, Julius

    2015-01-01

    Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genomic pathway of testosterone and estradiol in the amygdala in relation to anxiety and depressive-like behavior. Sham-operated and gonadectomized male rats (GDX) supplemented with testosterone propionate, estradiol, or olive oil were used. Five minutes after administration, anxiety ...

  6. Carotenoids, birdsong and oxidative status: administration of dietary lutein is associated with an increase in song rate and circulating antioxidants (albumin and cholesterol and a decrease in oxidative damage.

    Directory of Open Access Journals (Sweden)

    Stefania Casagrande

    Full Text Available Despite the appealing hypothesis that carotenoid-based colouration signals oxidative status, evidence supporting the antioxidant function of these pigments is scarce. Recent studies have shown that lutein, the most common carotenoid used by birds, can enhance the expression of non-visual traits, such as birdsong. Nevertheless, the underlying physiological mechanisms remain unclear. In this study we hypothesized that male European starlings (Sturnus vulgaris fed extra lutein increase their song rate as a consequence of an improved oxidative status. Although birdsong may be especially sensitive to the redox status, this has, to the best of our knowledge, never been tested. Together with the determination of circulating oxidative damage (ROMs, reactive oxygen metabolites, we quantified uric acid, albumin, total proteins, cholesterol, and testosterone, which are physiological parameters potentially sensitive to oxidation and/or related to both carotenoid functions and birdsong expression. We found that the birds fed extra lutein sang more frequently than control birds and showed an increase of albumin and cholesterol together with a decrease of oxidative damage. Moreover, we could show that song rate was associated with high levels of albumin and cholesterol and low levels of oxidative damage, independently from testosterone levels. Our study shows for the first time that song rate honestly signals the oxidative status of males and that dietary lutein is associated with the circulation of albumin and cholesterol in birds, providing a novel insight to the theoretical framework related to the honest signalling of carotenoid-based traits.

  7. The roles of testosterone and cortisol in friendship formation.

    Science.gov (United States)

    Ketay, Sarah; Welker, Keith M; Slatcher, Richard B

    2017-02-01

    Although research has investigated the neuroendocrine correlates of romantic relationships, the neuroendocrine correlates of friendship formation are largely unexplored. In two conditions, participants' salivary testosterone and cortisol were measured before and after a high versus low closeness activity with another same-sex participant. In the high closeness task, participants took turns answering questions that fostered increases in self-disclosure. The low closeness task fostered low levels of self-disclosure. Dyadic multilevel models indicated that lower basal testosterone and decreases in testosterone were associated with increased closeness between recently acquainted strangers. Our results suggest that people high in testosterone felt less close to others and desired less closeness. Further, lower basal cortisol and dynamic cortisol decreases were associated with greater closeness and desired closeness in the high closeness condition. Finally, we found that the partners of those who had lower cortisol desired more closeness. These findings suggest that lower testosterone and cortisol are linked to the facilitation of initial social bonds and that these social bonds may, in turn, be associated with changes in these hormones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism.

    Science.gov (United States)

    Graves, Steven M; Clark, Mary J; Traynor, John R; Hu, Xiu-Ti; Napier, T Celeste

    2015-02-01

    Methamphetamine profoundly increases brain monoamines and is a widely abused psychostimulant. The effects of methamphetamine self-administration on neuron function are not known for the nucleus accumbens, a brain region involved in addictive behaviors, including drug-seeking. One therapeutic target showing preclinical promise at attenuating psychostimulant-seeking is 5-HT2C receptors; however, the effects of 5-HT2C receptor ligands on neuronal physiology are unclear. 5-HT2C receptor agonism decreases psychostimulant-mediated behaviors, and the putative 5-HT2C receptor inverse agonist, SB 206553, attenuates methamphetamine-seeking in rats. To ascertain the effects of methamphetamine, and 5-HT2C receptor inverse agonism and agonism, on neuronal function in the nucleus accumbens, we evaluated methamphetamine, SB 206553, and the 5-HT2C receptor agonist and Ro 60-0175, on neuronal excitability within the accumbens shell subregion using whole-cell current-clamp recordings in forebrain slices ex vivo. We reveal that methamphetamine self-administration decreased generation of evoked action potentials. In contrast, SB 206553 and Ro 60-0175 increased evoked spiking, effects that were prevented by the 5-HT2C receptor antagonist, SB 242084. We also assessed signaling mechanisms engaged by 5-HT2C receptors, and determined that accumbal 5-HT2C receptors stimulated Gq, but not Gi/o. These findings demonstrate that methamphetamine-induced decreases in excitability of neurons within the nucleus accumbens shell were abrogated by both 5-HT2C inverse agonism and agonism, and this effect likely involved activation of Gq-mediated signaling pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

    Science.gov (United States)

    Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-07-01

    This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging.

  10. The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.

    Science.gov (United States)

    Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

    2015-02-01

    For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines

  11. Testosterone undecanoate and depo medroxyprogesterone acetate induced azoospermia through increased expression of spermatogenic cell caspase 3

    Directory of Open Access Journals (Sweden)

    Nukman Moeloek

    2008-09-01

    Full Text Available The administration of a combination of testosterone undecanoate (TU, a long-acting androgen and depo-medroxyprogesterone acetate (DMPA were investigated in term of suppression of rat sperm concentration in vivo to azoospermia through increasing activity of spermatogenic cell caspase 3. Adult Sprague Dawley rats received TU and DMPA of 2.5 mg and 1.25 mg, respectively, a regimen known to rapidly reduce intra testicular testosterone and to produce azoospermia within 12 weeks. Caspase 3 positive sperm cells increased compared with control levels during 6 weeks post-injection and increased further through 60 weeks. Immunohistochemistry for caspase 3 revealed that spermatocytes represented the predominant caspase 3 positive germ cells. Modest immunoreactivity for caspase-3 was localized to nuclear region of the germ cells of control and treated testes. Immunohistochemistry study revealed significantly increased caspase-3 expression in nuclei of germ cells during administration of TU+DMPA to rats. Additionally, the caspase 3 content was significantly increased in germ cells during rats were administered TU+DMPA (453.90±84.88 cells/200 seminiferous tubules and caspase 3 significant increase in immunoreactivity was localized to the nuclei of spermatogonia, spermatocytes, and spermatids. Taken together, these results indicated that azoospermia due to reduced intratesticular testosterone concentration was caspase-3 activation dependent and suggested that the increase in active caspase-3 in the nucleus may be involved in the induction of decreased sperm production. (Med J Indones 2008; 17: 149-56Keywords: TU, DMPA, sperm concentration, germ cells

  12. Determination of testosterone esters in the hair of male greyhound dogs using liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Devi, Jayasree Leela; Zahra, Paul; Vine, John H; Whittem, Ted

    2017-06-28

    The doping of greyhound dogs with testosterone is done in an attempt to improve their athletic performance, but such doping cannot easily be confirmed, especially in male dogs owing to the natural presence of endogenous testosterone. As testosterone is usually administered as its esters, their direct detection in hair would provide confirmatory evidence of the administration of a pharmaceutical product. This article demonstrates that the use of a liquid chromatography-high resolution mass spectrometry method with heated electrospray ionisation (HESI) combined with the use of amino solid-phase extraction (SPE) cartridges for sample clean-up, is suitable for the sensitive determination of propionate, phenyl propionate, isocaproate, decanoate, and enanthate esters of testosterone in greyhound hair. The method is linear over the range, 0.1 μg/kg-10 μg/kg, for all the testosterone esters analysed. The limits of detection (LOD) are 0.05 μg/kg for testosterone phenyl propionate, isocaproate, and decanoate, 0.025 μg/kg for testosterone propionate, and 0.25 μg/kg for testosterone enanthate. This method was applied to hair samples collected from male greyhounds before and after a single administration of a product containing several testosterone esters, each of which could be detected up to 100 days post-administration. The study also demonstrates that tail hair is the specimen of choice for the analysis of testosterone in dog hair and that washing of dogs does not impact the analysis of testosterone esters in hair. This method may be useful in racing regulation for the detection of illegitimate use of testosterone in all species. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

    Directory of Open Access Journals (Sweden)

    Dániel eVarga

    2015-06-01

    Full Text Available L-Kynurenine (L-KYN is a central metabolite of tryptophan degradation through the kynurenine pathway (KP. The systemic administration of L-KYN sulfate (L-KYNs leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA. An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs.In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i. p. would produce alterations in behavioral tasks (open field or object recognition in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus.We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice.

  14. The neuropeptide-Y Y5 receptor antagonist L-152,804 decreases alcohol self-administration in inbred alcohol-preferring (iP) rats.

    Science.gov (United States)

    Schroeder, Jason P; Overstreet, David H; Hodge, Clyde W

    2005-07-01

    Neuropeptide-Y (NPY) is the most abundant and widely distributed peptide in the mammalian central nervous system and increases feeding behavior through actions at the Y5 receptor subtype. Recent pharmacological evidence indicates that NPY activity at this receptor subtype can modulate ethanol reinforcement. The purpose of this study was to determine if NPY Y5 receptor antagonism reduces ethanol self-administration and reinforcement in a rodent genetic animal model of alcoholism. Selectively inbred alcohol-preferring (iP) rats were trained to voluntarily consume ethanol (10% vol/vol) versus H2O in a 24-h two-bottle choice test. An additional group of iP rats was trained in operant ethanol self-administration to lever press on a fixed-ratio 1 schedule for ethanol (10% vol/vol) reinforcement. Following establishment of baseline intake or ethanol-reinforced responding, iP rats were injected with L-152,804 (0-20 mg/kg) prior to two-bottle or operant ethanol self-administration sessions. In the two-bottle choice test, L-152,804 (3 and 10 mg/kg, ip) significantly reduced ethanol intake (g/kg) at 4- and 6-h postinjection and had no effect on food intake. In the operant procedure, L-152,804 (10 and 20 mg/kg, ip) significantly reduced both the dosage of self-administered ethanol (g/kg/1-h) and the total number of ethanol-reinforced responses. No effect was observed on latency to the first response or the number of inactive lever presses. These results indicate that blockade of NPY Y5 receptor activity decreases both voluntary ethanol drinking and ethanol reinforcement in a rodent genetic animal model of alcoholism. For this reason, NPY Y5 receptor antagonists may be useful in medical management of alcohol abuse and alcoholism in the human population.

  15. A Case of Thyroid Papillary Carcinoma: Remarkable Decrease in Multiple Lung Metastases within 40 Years after a Single Administration of Radioiodine without Thyroidectomy and with Later Anaplastic Transformation

    Directory of Open Access Journals (Sweden)

    Chio Okuyama

    2017-10-01

    Full Text Available Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.

  16. Oral administration of soluble β-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice.

    Science.gov (United States)

    Masuda, Yuki; Inoue, Hiroko; Ohta, Hiroya; Miyake, Ayumi; Konishi, Morichika; Nanba, Hiroaki

    2013-07-01

    Maitake D (MD)-Fraction is a highly purified soluble β-glucan derived from Grifola frondosa (an oriental edible mushroom). Intraperitoneal (i.p.) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system. In this study, we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models. After oral administration, MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells (DCs) present in the Peyer's patch. The captured MD-Fraction was then transported to the spleen, thereby inducing the systemic immune response. Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway. The therapeutic response of orally administered MD-Fraction was associated with (i) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs, (ii) increased infiltration of the activated T cells into the tumor and (iii) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer. Copyright © 2012 UICC.

  17. Systemic treatment with epidermal growth factor but not insulin-like growth factor I decreases the involution of the prostate in castrated rats

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Sørensen, Flemming Brandt

    2000-01-01

    -linked immunosorbent assay (ELISA). Treatment with EGF inhibited the involution of the prostate (P cellular...... proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration....... Compared with testosterone, the effects of EGF treatment on the prostate involution were moderate, and the effects of EGF were not related to cellular proliferation....

  18. Activational action of testosterone on androgen receptors protects males preventing temporomandibular joint pain.

    Science.gov (United States)

    Fanton, L E; Macedo, C G; Torres-Chávez, K E; Fischer, L; Tambeli, C H

    2017-01-01

    Testosterone protects male rats from Temporomandibular Joint (TMJ) pain. This study investigated whether this protective effect is mediated by an organizational action of testosterone during nervous system development, by central estrogen and androgen receptors and by the 5α-reduced metabolite of testosterone, dihydrotestosterone. A pharmacological approach was used to assess the ability of the androgen receptor antagonist flutamide, the estrogen receptor antagonist ICI 182 780 and the 5-α reductase inhibitor dutasteride to block the protective effect of testosterone, evaluated through the behavioral response induced by a TMJ injection of 0.5% formalin. Flutamide and ICI 182 780 were injected into the medullary subarachnoid space, and dutasteride and testosterone were systemically administered. The TMJ injection of 0.5% formalin induced a significant nociceptive behavioral response in gonadectomized male and naïve female, but not in sham gonadectomized male rats, confirming that endogenous testosterone prevents TMJ nociception in males. Testosterone administration prevented formalin-induced TMJ nociception in males gonadectomized either in the neonatal (at the day of birth) or adult period and in naïve female rats, suggesting that the protective effect of testosterone on TMJ nociception does not depend on its organizational actions during critical periods of development. The administration of flutamide and dutasteride but not of ICI 182 780 blocked the protective effect of testosterone. We conclude that the protective effect of testosterone on TMJ nociception depends on activational actions of dihydrotestosterone on androgen receptors rather than on organizational androgenic actions during central nervous system development or estrogenic actions. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Testosterone deficiency: a historical perspective

    Directory of Open Access Journals (Sweden)

    Eberhard Nieschlag

    2014-02-01

    Full Text Available The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial (and other oriental courts employed castrates as overseers in harems who often obtained high-ranking political positions. The era of testis transplantation and organotherapy was initiated by John Hunter in London who transplanted testes into capons in 1786. The intention of his experiments was to prove the 'vital principle' as the basis for modern transplantation medicine, but Hunter did not consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849 in Göttingen and is thus considered the father of endocrinology. Following his observations, testicular preparations were used for therapy, popularized by self-experiments by Charles-Edouard Brown-Séquard in Paris (1889, which can at best have placebo effects. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproved. Today testicular transplantation is being refined by stem cell research and germ cell transplantation. Modern androgen therapy started in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam. In the same year testosterone was chemically synthesized independently by Adolf Butenandt in Göttingen and Leopold Ruzicka in Basel. Since testosterone was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl testosterone, now obsolete because of liver toxicity. The early phases of testosterone treatment coincide with the first description of the most prominent syndromes of hypogonadism by Klinefelter, by

  20. Efek ekstrak akar ginseng Jawa dan Korea terhadap libido mencit jantan pada prakondisi testosteron rendah

    Directory of Open Access Journals (Sweden)

    Dwi Winarni

    2012-02-01

    Full Text Available This research was designed to compare the potency and duration effect of Java ginseng and Korean ginseng root extract administration on sexual behavior of male mice. It was done experimentally on male mice (strain BALB, aged 8–10 weeks, weighed 25–35 g. Thirty eight mice were grouped to 4 (four groups: First group was treated with solvent (as positive control, 2nd group was treated ethynilestradiol (EE2 (as negative control, 3rd group was treated with Java ginseng root extract, and 4th group was treated with Korean ginseng root extract. All groups were administered with EE2 0.56 mg/20 g bw/day for 9 days as pretreatment to decrease the testosteron level. After pretreatment, each group divided to 3 subgroups (each would receive treatment for 9, 18, and 27 days. Ethynilestradiol 0.56 mg/20 g bw/day was administered along treatment to keep testosterone level low, except to positive control group. Java ginseng and Korean ginseng root extract (equal with 1.4 mg ginseng root powder/ 20 g bw/day and EE2 were administered orally. The level of testosterone after pretreatment was measured by RIA (radioimmuoassay and changes in libido were determined by libido test. After the last treatment, 1 male mouse kept singly in individual cage. Libido test was carried out for 20 minutes. All of these activities during test recorded by handycam. The mice were observed for time from the introduction of female into the cage of male upto the first mount (mounting latency/ ML and for the number of mounts (mounting frequency/MF. The results indicated that at low testosterone level, Java ginseng root extract administration at the dose equal with 1.4 mg ginseng root powder/20 g bw/day shortened mounting latency and increased mounting frequency but Korean ginseng extract root at the same dose gave negative effects. Duration of administration of both Java and Korean ginseng root extract didn’t give effect on libido.

  1. Neuroprotective effects of testosterone treatment in men with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Florian Kurth

    2014-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory and neurodegenerative disease of the central nervous system. While current medication reduces relapses and inflammatory activity, it has only a modest effect on long-term disability and gray matter atrophy. Here, we have characterized the potential neuroprotective effects of testosterone on cerebral gray matter in a pilot clinical trial. Ten men with relapsing–remitting MS were included in this open-label phase II trial. Subjects were observed without treatment for 6 months, followed by testosterone treatment for another 12 months. Focal gray matter loss as a marker for neurodegeneration was assessed using voxel-based morphometry. During the non-treatment phase, significant voxel-wise gray matter decreases were widespread (p≤ 0.05 corrected. However, during testosterone treatment, gray matter loss was no longer evident. In fact, a significant gray matter increase in the right frontal cortex was observed (p≤ 0.05 corrected. These observations support the potential of testosterone treatment to stall (and perhaps even reverse neurodegeneration associated with MS. Furthermore, they warrant the investigation of testosterone's neuroprotective effects in larger, placebo controlled MS trials as well as in other neurodegenerative diseases. This is the first report of gray matter increase as the result of treatment in MS.

  2. Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep.

    Science.gov (United States)

    Chowdhuri, Susmita; Bascom, Amy; Mohan, David; Diamond, Michael P; Badr, M Safwan

    2013-12-01

    Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. Randomization to oral finasteride vs. sham, single-center study. Sleep research laboratory. Fourteen healthy young males without sleep apnea. Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. The apnea threshold (AT) was defined as the end-tidal CO₂(P(ET)CO₂) that demarcated the central apnea closest to the eupneic P(ET)CO₂. The CO₂ reserve was defined as the difference in P(ET)CO₂ between eupnea and AT. The apneic threshold and CO₂ reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO₂ reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations.

  3. Testosterone reduces amygdala-orbitofrontal cortex coupling.

    NARCIS (Netherlands)

    Wingen, G.A. van; Mattern, C.; Verkes, R.J.; Buitelaar, J.K.; Fernandez, G.S.E.

    2010-01-01

    Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered

  4. Testosterone reduces amygdala-orbitofrontal cortex coupling

    NARCIS (Netherlands)

    van Wingen, Guido; Mattern, Claudia; Verkes, Robbert Jan; Buitelaar, Jan; Fernández, Guillén

    2010-01-01

    Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered

  5. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Science.gov (United States)

    Purves-Tyson, Tertia D; Owens, Samantha J; Double, Kay L; Desai, Reena; Handelsman, David J; Weickert, Cynthia Shannon

    2014-01-01

    Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s) by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase), breakdown (catechol-O-methyl transferase; monoamine oxygenase), transport [vesicular monoamine transporter (VMAT), dopamine transporter (DAT)] and receptors (DRD1-D5)] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen receptor

  6. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Directory of Open Access Journals (Sweden)

    Tertia D Purves-Tyson

    Full Text Available Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase, breakdown (catechol-O-methyl transferase; monoamine oxygenase, transport [vesicular monoamine transporter (VMAT, dopamine transporter (DAT] and receptors (DRD1-D5] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen

  7. Testosterone Deficiency - Establishing A Biochemical Diagnosis

    OpenAIRE

    Krakowsky, Yonah; Grober, Ethan D.

    2015-01-01

    Testosterone deficiency is a common and often unrecognized disorder impacting the lives of many men. Symptoms related to low testosterone are relatively non-specific and clinicians must therefore ensure that a patients? symptomatology is supported by a biochemical profile suggestive of testosterone deficiency. There are many options available to determine a patient?s testosterone level and laboratories will vary in the type of biochemical assessment they provide. In assessing patients with su...

  8. Gender-Typed Play and Amniotic Testosterone

    Science.gov (United States)

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  9. Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease.

    Science.gov (United States)

    Kanoke, Atsushi; Fujimura, Miki; Niizuma, Kuniyasu; Fujimura, Taku; Kakizaki, Aya; Ito, Akira; Sakata, Hiroyuki; Sato-Maeda, Mika; Kure, Shigeo; Tominaga, Teiji

    2016-07-01

    Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by an abnormal vascular network at the base of the brain. Recent studies identified the RNF213 gene (RNF213) as an important susceptibility gene for MMD; however, the mechanisms underlying the RNF213 abnormality related to MMD have not yet been elucidated. We previously reported that Rnf213-deficient mice and Rnf213 p. R4828K knock-in mice did not spontaneously develop MMD, indicating the importance of secondary insults in addition to genetic factors in the pathogenesis of MMD. The most influential secondary insult is considered to be an immunological reaction because RNF213 is predominantly expressed in immunological tissues. Therefore, we herein attempted to evaluate the role of an immunological stimulation as a supplementary insult to the target disruption of RNF213 in the pathophysiology of MMD. Rnf213-deficient mice were treated with strong immunological adjuvants including muramyl dipeptide (MDP)-Lys (L18), and then underwent time-sequential magnetic resonance angiography (MRA) up to 40 weeks of age. The results obtained did not reveal any characteristic finding of MMD, and no significant difference was observed in MRA findings or the anatomy of the circle of Willis between Rnf213-deficient mice and wild-type mice after the administration of MDP-Lys (L18). The ratio of regulatory T cells after the administration of MDP-Lys (L18) was significantly decreased in Rnf213-deficient mice (p<0.01), suggesting the potential role of the RNF213 abnormality in the differentiation of regulatory T cells. Although the mechanisms underlying the development of MMD currently remain unclear, the RNF213 abnormality may compromise immunological self-tolerance, thereby contributing to the development of MMD. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

    Directory of Open Access Journals (Sweden)

    Dantzer Robert

    2011-02-01

    Full Text Available Abstract Exogenous administration of insulin-like growth factor (IGF-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng was administered intracerebroventricularly (i.c.v. to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng. Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST. Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß, tumor necrosis factor-(TNFα, inducible nitric oxide synthase (iNOS and glial fibrillary acidic protein (GFAP. Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.

  11. Modulating testosterone pathway: a new strategy to tackle male skin aging?

    OpenAIRE

    Bernard P; Scior T; Do QT

    2012-01-01

    Philippe Bernard1, Thomas Scior2, Quoc Tuan Do11Greenpharma SAS, Orléans, France; 2Pharmacy Department, Benemerita Universidad Autonoma de Puebla, Puebla, MexicoAbstract: In men, the level of testosterone decreases with age. At the skin level, the result is observed as a decrease in density and in a lower elasticity. Identifying compounds that are able to increase the level of testosterone appears to be an attractive strategy to develop new antiaging bioactive ingredients for men. ...

  12. Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA).

    Science.gov (United States)

    Heijboer, Annemieke C; Zimmerman, Yvette; de Boer, Theo; Coelingh Bennink, Herjan; Blankenstein, Marinus A

    2014-03-20

    Total testosterone is considered to be decreased during the use of combined oral contraceptives. There is, however, considerable concern about the quality of testosterone assays, especially at low levels. We aimed to confirm testosterone levels measured by direct radioimmunoassay in a recent clinical trial with a state-of-the-art LC-MSMS method. Surplus specimens with known testosterone levels collected during the study (Clinical Trial Registration number ISRCTN06414473) were reanalyzed with an LC-MSMS method. This method was compared to another LC-MSMS method that had shown to concur excellently to a reference method. Follow-up experiments were designed to explain the results. In contrast to our expectation, LC-MSMS measurements did not corroborate the data obtained by radioimmunoassay. Subsequent experiments showed that this could be attributed to a strong dependency of the radioimmunoassay on SHBG. Testosterone results (n = 198) obtained by direct radioimmunoassay showed a negative correlation to SHBG levels (r = -0.676; p<0.001). By contrast, testosterone results obtained by LC-MSMS were not related to SHBG (r = 0.100; NS). In conclusion, our results indicate that total testosterone measurements during oral contraceptive use are unreliable when performed with assays sensitive to the SHBG concentration. The discrepancy with the literature can most likely be explained by the sensitivity of the immunoassay used to SHBG. Given the sharp increase in SHBG during the use of many oral contraceptives, total testosterone may not decrease, whereas its bioavailability, estimated by free testosterone levels, will be diminished. Studies aiming at restoration of testosterone homeostasis during oral contraception need to take this into account. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Low free testosterone predicts frailty in older men: the health in men study.

    Science.gov (United States)

    Hyde, Zoë; Flicker, Leon; Almeida, Osvaldo P; Hankey, Graeme J; McCaul, Kieran A; Chubb, S A Paul; Yeap, Bu B

    2010-07-01

    The prevalence of frailty increases, whereas testosterone decreases, as men age. Low testosterone may be a risk factor for development of this syndrome. Our objective was to determine whether testosterone levels are associated with frailty. We conducted a prospective cohort study. Between 2001 and 2004, frailty was assessed in 3616 community-dwelling men aged 70-88 yr. Frailty was reassessed in 1586 men aged 76-93 yr in 2008-2009. Frailty was assessed with the FRAIL scale, comprising five domains: fatigue, difficulty climbing a flight of stairs, difficulty walking more than 100 m, more than five illnesses present, or weight loss greater than 5%. Testosterone, SHBG, and LH were assayed at baseline. Free testosterone was calculated using mass action equations. At baseline, 15.2% of men (n = 548) were frail (at least three deficits), increasing to 23.0% (n = 364) at follow-up. At baseline, each 1 sd decrease in total or free testosterone level was associated with increased odds of frailty [odds ratio (OR) = 1.23; 95% confidence interval (CI) = 1.11-1.38, and OR = 1.29; 95% CI = 1.15-1.44 for total and free testosterone, respectively]. Lower LH was associated with reduced odds of frailty (OR = 0.88; 95% CI = 0.81-0.95). Adjustments were made for age, body mass index, smoking, diabetes, social support, and other covariates. At follow-up, only lower free testosterone levels (OR = 1.22; 95% CI = 1.05-1.42) predicted frailty. Lower free testosterone was independently associated with frailty at baseline and follow-up. Randomized trials should explore whether testosterone therapy can prevent the development of frailty.

  14. Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

    Science.gov (United States)

    Lau, Chi-Fai; Ho, Yuen-Shan; Hung, Clara Hiu-Ling; Poon, Chun-Hei; Chiu, Kin; Yang, Xifei

    2014-01-01

    Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer's disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD. PMID:25045655

  15. Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Chi-Fai Lau

    2014-01-01

    Full Text Available Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD, there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ, but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

  16. The hidden dimensions of the competition effect: basal cortisol and basal testosterone jointly predict changes in salivary testosterone after social victory in men.

    Science.gov (United States)

    Zilioli, Samuele; Watson, Neil V

    2012-11-01

    Dominance struggles appear to affect hormone concentrations in many mammalian species, such that higher concentrations of testosterone are seen in winners of competitions, compared to losers. This so-called, "competition effect" has received inconsistent empirical support, suggesting that additional psychological (e.g., mood), situational (i.e., nature of the competition) and physiological (e.g., cortisol) variables might intervene in modulating testosterone fluctuations after social contests. We investigated possible interactions between the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-adrenal (HPA) stress axis in predicting transient changes in testosterone after social victory or defeat on a familiar competitive task. In particular, the present study examined the dual-hormone hypothesis - proposing that baseline cortisol potently modulates the competition effect (Mehta and Josephs, 2010) - in a sample of healthy young men engaged in head-to-head competition on a widely played commercial videogame, Tetris. We found a significant interaction between HPG and HPA axes status and the competition effect on testosterone in the randomly assigned videogame winners, such that winners with a pre-competition combination of high baseline testosterone and low baseline cortisol exhibited significantly greater post-competition testosterone concentrations. The randomly assigned videogame losers showed significantly decreased post-competition levels of testosterone. Possible biological and evolutionary mechanisms underlying this phenomenon are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  18. Testosterone in biosociology: A memoir.

    Science.gov (United States)

    Mazur, Allan

    2017-06-01

    A contribution to a special issue on Hormones and Human Competition. The author looks back at his four decades of research on testosterone in the context of biosociology - its accomplishments, pitfalls, outstanding questions, and future directions. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Encapsulation of testosterone by chitosan nanoparticles.

    Science.gov (United States)

    Chanphai, P; Tajmir-Riahi, H A

    2017-05-01

    The loading of testosterone by chitosan nanoparticles was investigated, using multiple spectroscopic methods, thermodynamic analysis, TEM images and modeling. Thermodynamic parameters showed testosterone-chitosan bindings occur mainly via H-bonding and van der Waals contacts. As polymer size increased more stable steroid-chitosan conjugates formed and hydrophobic contact was also observed. The loading efficacy of testosterone-nanocarrier was 40-55% and increased as chitosan size increased. Testosterone encapsulation markedly alters chitosan morphology. Chitosan nanoparticles are capable of transporting testosterone in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Systemic treatment with Epidermal Growth Factor (EGF)but not Insulin like Growth Factor (IGF-I) decrease the involution of the Prostate in Castrated Rats

    DEFF Research Database (Denmark)

    Tørring, Niels; Lars, Vinter-Jensen; Sørensen, Flemming Brandt

    2000-01-01

    Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrated...... Wistar rats were treated with growth factors (EGF 35 microg/rat per day; IGF-I 350 microg/rat per day) or testosterone (2 mg/rat per day) for 3 days either immediately after or 10 days after castration. Prostate tissue was examined by stereological and immunohistochemical techniques and by enzyme...... proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration...

  1. Systemic treatment with epidermal growth factor but not insulin-like growth factor I decreases the involution of the prostate in castrated rats

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Sørensen, Flemming Brandt

    2000-01-01

    Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrated...... Wistar rats were treated with growth factors (EGF 35 microg/rat per day; IGF-I 350 microg/rat per day) or testosterone (2 mg/rat per day) for 3 days either immediately after or 10 days after castration. Prostate tissue was examined by stereological and immunohistochemical techniques and by enzyme...... proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration...

  2. Testosterone in women-the clinical significance

    DEFF Research Database (Denmark)

    Davis, Susan R; Jacobsen, Sarah Wåhlin

    2015-01-01

    Testosterone is an essential hormone for women, with physiological actions mediated directly or via aromatisation to oestradiol throughout the body. Despite the crucial role of testosterone and the high circulating concentrations of this hormone relative to oestradiol in women, studies of its...... action and the effects of testosterone deficiency and replacement in women are scarce. The primary indication for the prescription of testosterone for women is loss of sexual desire, which causes affected women substantial concern. That no formulation has been approved for this purpose has not impeded...... the widespread use of testosterone by women-either off-label or as compounded therapy. Observational studies indicate that testosterone has favourable cardiovascular effects measured by surrogate outcomes; however, associations between endogenous testosterone and the risk of cardiovascular disease and total...

  3. Reduction of calprotectin and phosphate during testosterone therapy in aging men: a randomized controlled trial.

    Science.gov (United States)

    Pedersen, L; Christensen, L L; Pedersen, S M; Andersen, M

    2017-05-01

    To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 (FGF23), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. Randomized, double-blinded, placebo-controlled study. Odense Androgen Study-the effect of Testim and training in hypogonadal men. Men aged 60-78 years old with a low normal concentration of free of bioavailable testosterone 94 cm recruited from 2008 to 2009 (N = 48) by advertisement. Participants were randomized to receive 5-10 g gel/50-100 mg testosterone (Testim®, Ipsen, France) or 5-10 g gel/placebo. The plasma levels of calprotectin and phosphate were significantly reduced in the group receiving testosterone therapy (gel) compared to the placebo group (p Testosterone treatment did not have any significant effect on plasma levels of FGF23 or soluble Klotho. The reduction in phosphate levels was inversely associated with bioavailable testosterone. Compared to the placebo group, 6 months of testosterone therapy (gel) reduced calprotectin and phosphate levels suggesting decreased inflammation and decreased cardiovascular risk.

  4. Association of Obesity-Related Hemodilution of Prostate-Specific Antigen, Dihydrotestosterone, and Testosterone.

    Science.gov (United States)

    Klaassen, Zachary; Howard, Lauren E; Moreira, Daniel M; Andriole, Gerald L; Terris, Martha K; Freedland, Stephen J

    2017-04-01

    Prostate-specific antigen (PSA) hemodilution is the leading theory for lower PSA values in obese men. However, testosterone and dihydrotestosterone (DHT), which are necessary for PSA production, are reduced in obese men. We assessed the relationship of body mass index (BMI) and PSA, taking into consideration the effect of testosterone and DHT. Among 8,122 participants in Reduction by Dutasteride of Prostate Cancer Events (REDUCE), complete data were available for 7,275. BMI was categorized as normal (testosterone, and DHT and the outcome variable of PSA were examined using linear regression. There were 1,964 (27.0%) normal weight, 3,826 (52.6%) overweight, 1,200 (16.5%) obese, and 285 (3.9%) moderately + severely obese patients. With increasing BMI, there was a progressive decrease in PSA (P = 0.02), increase in prostate volume (P testosterone (P testosterone and DHT, as well as when adjusting for testosterone and DHT in the same model. Decreased androgen levels accounted for only 19% of the lower PSA in men with higher BMI. Only a fraction of lower PSA in obese men could be attributed to testosterone and DHT levels. The remaining factors explaining lower PSA are unaccounted for, presumably secondary to hemodilution associated with increased plasma volume in obese men. Prostate 77:466-470, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity.

    Science.gov (United States)

    Kooptiwut, Suwattanee; Hanchang, Wanthanee; Semprasert, Namoiy; Junking, Mutita; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2015-03-01

    Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin-angiotensin-aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47(phox) mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47(phox) mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47(phox). In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway. © 2015 Society for

  6. Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    C.Q. Conceição

    2017-11-01

    Full Text Available The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days. After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

  7. Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats.

    Science.gov (United States)

    Conceição, C Q; Engi, S A; Cruz, F C; Planeta, C S

    2017-11-17

    The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

  8. Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse.

    Directory of Open Access Journals (Sweden)

    Olivier Salamin

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that regulate gene expression and thus influence many cellular and physiological processes. miRNAs are also present in cell-free body fluids such as plasma or serum, and these circulating miRNAs are very stable, sensitive, and specific biomarkers of pathophysiological states. In this study, we investigated whether circulating miRNAs could serve as biomarkers of exogenous testosterone administration. Misuse of testosterone as a performance-enhancing drug is thought to be widespread in sports. Detection of testosterone through the urinary steroid profile of the Athlete Biological Passport faces several obstacles, indicating that new biomarkers are required. To this end, we analyzed plasma miRNA levels by high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after transdermal and oral testosterone administration. Screening identified three potential candidate miRNAs that were altered by both routes of testosterone administration. Longitudinal monitoring of these candidates revealed that variation in two of them (miR-150 and miR-342, relative to the corresponding levels in control samples, was testosterone-independent. However, levels of the liver-specific miR-122 increased 3.5-fold 1 day after drug intake. Given that testosterone is metabolized by the liver, this observation suggests that miR-122 in cell-free fluids may be used as a sensitive biomarker of testosterone misuse via multiple dosing routes and could therefore be integrated into a blood-based multiparametric follow-up.

  9. Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats

    National Research Council Canada - National Science Library

    Tang-Christensen, Mads; Vrang, Niels; Ortmann, Sylvia; Bidlingmaier, Martin; Horvath, Tamas L; Tschöp, Matthias

    2004-01-01

    .... ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY...

  10. Maximal testosterone suppression in prostate cancer--free vs total testosterone.

    Science.gov (United States)

    Rove, Kyle O; Crawford, E David; Perachino, Massimo; Morote, Juan; Klotz, Laurence; Lange, Paul H; Andriole, Gerald L; Matsumoto, Alvin M; Taneja, Samir S; Eisenberger, Mario A; Reis, Leonardo O

    2014-06-01

    Testosterone remains a key target in the treatment of advanced prostate cancer. The relationship of free testosterone to prostate cancer treatment and outcomes remains largely unexplored. A consensus of prostate cancer experts was convened in 2013 to review current knowledge surrounding relationship of total and free testosterone to prostate cancer, discuss the free hormone hypothesis, and highlight future avenues for therapeutics. Free testosterone may better reflect prostate cancer tissue androgen levels than serum total testosterone concentration. Free testosterone deserves more research regarding its relation to clinical outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study

    National Research Council Canada - National Science Library

    Caminiti, Giuseppe; Volterrani, Maurizio; Iellamo, Ferdinando; Marazzi, Giuseppe; Massaro, Rosalba; Miceli, Marco; Mammi, Caterina; Piepoli, Massimo; Fini, Massimo; Rosano, Giuseppe M C

    2009-01-01

    This study investigated the effect of a 12-week long-acting testosterone administration on maximal exercise capacity, ventilatory efficiency, muscle strength, insulin resistance, and baroreflex sensitivity (BRS...

  12. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue

    2015-01-01

    PURPOSE: We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. METHODS: Double-blinded, placebo-controlled study in 54 men aged 60-78 years...... central fat mass (r = 0.84). CONCLUSIONS: Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass....

  13. The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Bennett, Patrick

    1988-01-01

    Seventy-three euthyroid male patients with alcoholic cirrhosis of the liver were randomly allocated to oral testosterone (200 mg t.i.d.) or placebo and followed for up to 36 months. Triiodothyronine (T3), tetraiodothyronine (T4), thyroxine binding globulin (TBG) and T4/TBG ratio were determined......, it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function...

  14. [Contribution of bioavailable testosterone assay for the diagnosis of androgen deficiency in elderly men].

    Science.gov (United States)

    Lejeune, H; Déchaud, H; Pugeat, M

    2003-04-01

    With age, some men develop symptoms resembling hypogonadism. Several cross-sectional and longitudinal studies have shown a decrease in testosterone levels with ageing in men. This finding has equally been observed in elderly men in good health. Testosterone levels decline progressively as of the thirties, at a rate which remains constant throughout life. While total testosterone levels decrease, sex hormone binding globulin (SHBG) levels on the contrary increase with age, with the result that the levels of free and non-SHBG-bound testosterone (corresponding to the fraction which is bioavailable to target cells) decrease more abruptly than that of total testosterone. Higher LH levels, decreased testosterone response to hCG and less Leydig cells all indicate that ageing induces partial testicular failure. However, the gonadotropic function is also affected in ageing. The hypothalamus-pituitary becomes more sensitive to gonad steroid feedback, LH pulse amplitude decreases, and the LH response to GnRH is blunted compared to the situation in young men. Thus LH level is not a valid index of androgen deficiency in elderly males. None of the androgen-dependent functions (libido, erection, sense of well-being, muscle mass and strength, fat mass, bone mass, erythropoiesis, etc.) are under exclusively androgen control, and there is no elderly male symptom which is completely specific to androgen deficiency. Thus, in elderly men, when clinical symptoms might indicate androgen deficiency, biological confirmation is needed. An assay which is independent of SHBG fluctuations is mandatory. Bioavailable testosterone assay by ammonium sulfate precipitation seems to us to be the optimum method for diagnosing androgen deficiency: it gives a reliable measurement for the testosterone fraction available to target cells, is adapted to clinical practice, and provides results that can be directly compared with current reference values for healthy young men.

  15. High free testosterone index increases lung function in adult males

    Directory of Open Access Journals (Sweden)

    Martiem Mawi

    2012-08-01

    Full Text Available Background Increasing age and decreased testosterone concentrations in males influence muscle strength and muscle mass, particularly in skeletal muscle. There have been few studies on decreased lung function resulting from reduced mass and strength of respiratory muscles. The aim of the present study was to investigate the existence of an association between free testosterone index (FTI and lung function in males aged between 40 and 80 years. Methods This cross-sectional study involved 167 males aged between 40 and 80 years in Cilandak subdistrict, South Jakarta. Total serum testosterone and sex hormone-binding globulin (SHBG concentrations were determined by electrochemiluminescence immunoassay (ECLIA using Roche Elecsys Reagent Kit Cat 11776061 and Elecsys 2010 reagent (Cobas e601, respectively FTI was calculated using the formula free testosterone/SHBG x 100%. Forced expiratory volume in 1 second (VEP1 was assessed by means of an AS 500 spirometer. Results Mean age of the subjects was 53.32 ± 8.26 years, mean total serum testosterone concentration was 532.59 ± 206.92 ng/dL, mean SHBG concentration 41.26 ± 21.14 nmol/L, mean FTI 48.22 ± 14.34 %, and mean VEP1 was 1.63 ± 0.54 L. There was a significant association between both SHBG and FTI on the one hand and VEP1 on the other, with Pearson correlation coefficients of -0.199 (p=0.010 and 0.271 (p=0.000, respectively. Linear multiple regression analysis indicated that FTI was the most influential variable on lung function (VEP1, higher FTI values indicating higher VEP1 (â=0.008: p=0.004. Conclusion In males aged 40-80 years, higher FTI values indicate better lung function as determined by means of VEP1.

  16. Marketing and Testosterone Treatment in the USA: A Systematic Review.

    Science.gov (United States)

    Bandari, Jathin; Ayyash, Omar M; Emery, Sherry L; Wessel, Charles B; Davies, Benjamin J

    2017-10-01

    Testosterone replacement therapy (TRT) is currently approved by the Food and Drug Administration only for classic hypogonadism, although off-label indications have resulted in a dramatic expansion in prescriptions in the USA. Marketing may significantly affect prescriber behavior. To systematically review all available evidence on marketing and TRT in the USA. PubMed, Embase, and Scopus were searched up to July 2017 for all relevant publications reporting on assessments of the TRT market size, economic costs associated with hypogonadism, trends in TRT prescriptions, drug discontinuation rates, and advertising and sales efforts in the USA. Twenty retrospective studies were included in the final analysis. The market size for hypogonadism constitutes 5.6-76.8% of men in the USA, with the lower end of the range representing the strictest criteria for diagnosis. Men with a diagnosis of hypogonadism consume $14 118 in direct and indirect costs to the payer. Over the last 2 decades, TRT prescriptions have increased between 1.8- and 4-fold. After 1 yr, 80-85% of men discontinue TRT. There is an association between direct-to-consumer advertising and testosterone testing, TRT prescriptions, and TRT without testosterone testing. There is a high prevalence of misinformation on Internet advertising. Off-label indications have driven the dramatic expansion of TRT prescriptions over the last 2 decades. Direct-to-consumer advertising poses a unique challenge in the USA. Overtreatment can be avoided by applying strict diagnostic criteria for hypogonadism, which limits the addressable market for TRT. In this report, we reviewed the relationship between marketing and testosterone therapy in the USA. We found that many patients are prescribed testosterone without an appropriate diagnosis of hypogonadism, which may be related to the marketing efforts for off-label prescribing. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  17. Testosterone suppresses oxidative stress via androgen receptor-independent pathway in murine cardiomyocytes.

    Science.gov (United States)

    Zhang, Li; Wu, Saizhu; Ruan, Yunjun; Hong, Lei; Xing, Xiaowen; Lai, Wenyan

    2011-01-01

    Evidence supports that oxidative stress exerts significant effects on the pathogenesis of heart dysfunction. On the other hand, the presence of specific androgen receptor (AR) in mammalian cardiomyocytes implies that androgen plays a physiological role in cardiac function, myocardial injury and the regulation of the redox state in the heart. This study used the testicular feminized (Tfm) and castrated male mice to investigate the effects of testosterone deficiency, physiological testosterone therapy and AR on oxidative stress in cardiomyocytes. Tfm mice have a non-functional AR and reduced circulating testosterone levels. Male littermates and Tfm mice were separated into 5 experimental groups: non-castrated littermate controls, castrated littermates, sham-operated Tfm, testosterone-treated castrated littermates and testosterone-treated sham-operated Tfm mice. Cardiomyocytes that were isolated from the left ventricle were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) enzyme activities, and malondialdehyde (MDA) levels. Additionally, mitochondrial DNA (mtDNA) deletion mutations were detected by nested PCR. The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the proportion of mtDNA mutations were increased in castrated and sham-operated Tfm mice compared to control mice. However, an increase was observed in the activities of SOD and GSH-Px enzyme as well as a decrease in MDA levels and the proportion of mtDNA mutations in the mice that had received testosterone therapy. These changes were statistically similar in castrated and sham-operated Tfm mice after testosterone therapy. In conclusion, it is testosterone deficiency that induces oxidative stress in cardiomyocytes. Physiological testosterone therapy is able to suppress oxidative stress mediated via the AR-independent pathway.

  18. Polycystic Ovary Induction in Mouse by Testosterone Enanthate

    Directory of Open Access Journals (Sweden)

    Zahra Kalhori

    2014-03-01

    Full Text Available Background &Objective: Polycystic ovary is the most common cause of infertility in Women. Animal models are required for understanding the pathogenesis of polycystic ovary. The objective of this study then was to develop an animal model for inducing the polycystic ovaries using testosterone enanthate.Materials & Methods: In this study, for inducing the polycystic ovary phenotype, female rats about12-14 days-old were injected daily with testosterone enanthate for 2 and 4 weeks (experiment groups: 1 and 2, while the control groups (1 and 2 were injected only with vehicle.The ovaries from both groups were fixed and then were used for histological studies.Results: Testosterone enanthate treatment causes the histological changes in mouse ovary and significantly increased the percentage of preantral and cystic follicles and decreased the percentage of antral follicles in the experiment group, comparing with the control group (P<0.05.Conclusion: It concluded that testosterone enanthate can induces polycystic ovary in mouse.

  19. The many faces of testosterone

    OpenAIRE

    Bain, Jerald

    2007-01-01

    Jerald BainDepartment of Medicine, Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario, CanadaAbstract: Testosterone is more than a “male sex hormone”. It is an important contributor to the robust metabolic functioning of multiple bodily systems. The abuse of anabolic steroids by athletes over the years has been one of the major detractors from the investigation an...

  20. 21 CFR 862.1680 - Testosterone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  1. Provider and Site-Level Determinants of Testosterone Prescribing in the Veterans Healthcare System.

    Science.gov (United States)

    Jasuja, Guneet K; Bhasin, Shalender; Rose, Adam J; Reisman, Joel I; Hanlon, Joseph T; Miller, Donald R; Morreale, Anthony P; Pogach, Leonard M; Cunningham, Francesca E; Park, Angela; Wiener, Renda S; Gifford, Allen L; Berlowitz, Dan R

    2017-09-01

    Testosterone prescribing rates have increased substantially in the past decade. However, little is known about the context within which such prescriptions occur. We evaluated provider- and site-level determinants of receipt of testosterone and of guideline-concordant testosterone prescribing. This study was cross-sectional in design. This study was conducted at the Veterans Health Administration (VA). Study participants were a national cohort of male patients who had received at least one outpatient prescription within the VA during fiscal year (FY) 2008 to FY 2012. A total of 38,648 providers and 130 stations were associated with these patients. This study measured receipt of testosterone and guideline-concordant testosterone prescribing. Providers ranging in age from 31 to 60 years, with less experience in the VA [all adjusted odds ratio (AOR), testosterone compared with older providers, providers of longer VA tenure, and primary care providers, respectively. Sites located in the West compared with the Northeast [AOR, 1.75; 95% confidence interval (CI), 1.45-2.11] and care received at a community-based outpatient clinic compared with a medical center (AOR, 1.22; 95% CI, 1.20-1.24) also predicted testosterone use. Although they were more likely to prescribe testosterone, endocrinologists were also more likely to obtain an appropriate workup before prescribing compared with primary care providers (AOR, 2.14; 95% CI, 1.54-2.97). Our results highlight the opportunity to intervene at both the provider and the site levels to improve testosterone prescribing. This study also provides a useful example of how to examine contributions to prescribing variation at different levels of the health care system.

  2. Influence of testosterone on mean arterial pressure: A physiological study in male and female normotensive WKY and hypertensive SHR rats.

    Science.gov (United States)

    Loh, S Y; Salleh, N

    2017-03-01

    Introduction Testosterone plays an important role in the blood pressure regulation. However, information with regard to the effect of this hormone on blood pressure in normotensive and hypertensive conditions is limited. Therefore, in this study, the relationship between plasma testosterone level and mean arterial pressure (MAP) was investigated under these conditions. Methods Normotensive Wistar-Kyoto (WKY) and hypertensive Spontaneous Hypertensive (SHR) male and female rats were gonadectomized with female rats treated with testosterone. Estrous cycle stages of intact female rats of both strains were identified by vaginal smear. Pressure in the carotid artery of anesthetized rats was measured via direct cannulation technique. The blood was withdrawn for plasma testosterone level measurement by enzyme-linked immunosorbent assay. Results Treatment of ovariectomized female WKY and SHR rats with testosterone for 6-week duration has resulted in MAP to increase (P testosterone levels decreased by orchidectomy (P testosterone levels were observed in intact female WKY and SHR rats between stages of the estrous cycle. Conclusions The effects seen in testosterone-treated ovariectomized female rats and in orchidectomized male rats suggested that testosterone could play an important role in causing the blood pressure to increase.

  3. Longitudinal relationships among endogenous testosterone, estradiol, and Quetelet index with high and low density lipoprotein cholesterols in adolescent boys.

    Science.gov (United States)

    Laskarzewski, P M; Morrison, J A; Gutai, J; Khoury, P R; Glueck, C J

    1983-08-01

    In a 1-year longitudinal study of 19 adolescent boys, our major aim was to assess whether, and to what degree, testosterone, estradiol, Quetelet index, and their interactions related to concentrations of high and low density lipoprotein cholesterol (HDLC, LDLC). During the 1-year followup, mean HDLC and estradiol levels fell and triglycerides, LDLC, Quetelet index, and testosterone levels rose. For large decreases in estradiol, increases in testosterone were associated with decreases in HDLC. These decreases in HDLC were moderated by small decreases in Quetelet index. For boys with small decreases in estradiol, as the changes in testosterone increased, the change in HDLC varied from an increase to a decrease, except in those boys who also had a small decrease in Quetelet index, for whom the change in HDLC was positive. The greatest increases in LDLC were observed in boys having the largest increase in Quetelet index and a small decrease in estradiol; however, as the decrease in estradiol became large, the positive association of Quetelet with LDLC was moderated or nullified. For boys having large decreases in estradiol, the LDLC/HDLC ratio changed from small increments to substantial decrements as testosterone increased. As the decreases in estradiol became smaller, increases in the change of testosterone moderated the decreases in the LDLC/HDLC ratio, and large increases in Quetelet index tended to diminish this moderation. As the change in testosterone increased, the change in triglyceride increased, unless the decrease in estradiol was small. The overall pattern of change of HDLC and LDLC during sexual maturation in boys can be associated with changes in testosterone, estradiol, and Quetelet index.

  4. Testosterone Deficiency, Cardiac Health, and Older Men

    Directory of Open Access Journals (Sweden)

    G. Hackett

    2014-01-01

    Full Text Available Low levels of testosterone are manifested by erectile dysfunction, reduced sexual desire, and loss of morning erections with increasing numbers of men are being diagnosed and require treatment. The prevalence rates of testosterone deficiency vary according to different studies but may be as high as 40% in populations of patients with type 2 diabetes. There is increasing evidence that testosterone deficiency is associated with increased cardiovascular and all-cause mortality. Screening for low testosterone is recommended in a number of high risk groups including those with type 2 diabetes and metabolic syndrome. There are recent data to suggest that testosterone replacement therapy may reduce cardiovascular mortality as well as improving multiple surrogate markers for cardiovascular events. Specific clinical trials of testosterone replacement therapy are needed in selected populations but in the meantime we must treat patients based on the best current evidence.

  5. Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men

    Science.gov (United States)

    Basaria, Shehzad; Traustadottir, Tinna; Harman, S. Mitchell; Pencina, Karol; Li, Zhuoying; Travison, Thomas G.; Miciek, Renee; Tsitouras, Panayiotis; Hally, Kathleen; Huang, Grace; Bhasin, Shalender

    2017-01-01

    Context: Findings of studies of testosterone’s effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied. Objective: To determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability, and physical function. Design, Setting, and Participants: This was a double-blind, placebo-controlled, randomized trial of healthy men ≥60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels testosterone or placebo gel daily for 3 years. Outcome Measures: Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months. Results: The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean estimated between-group difference, 10.7 W [95% confidence interval (CI), −4.0 to 25.5], P = 0.026; and 22.4 W [95% CI, 4.6 to 40.3], P = 0.027), respectively. Changes in chest-press strength (estimated mean difference, 16.3 N; 95% CI, 5.5 to 27.1; P testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group. Conclusion: Compared with placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass, and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied. PMID:27754805

  6. Performance of total testosterone measurement to predict free testosterone for the biochemical evaluation of male hypogonadism.

    Science.gov (United States)

    Anawalt, Bradley D; Hotaling, James M; Walsh, Thomas J; Matsumoto, Alvin M

    2012-04-01

    Guidelines recommend serum total testosterone measurement as the initial test to evaluate male hypogonadism, reserving free testosterone assessment for men with suspected sex hormone-binding globulin abnormalities or total testosterone near the lower limit of normal. We determined the performance of total testosterone measurement as a test to identify men with normal vs low free testosterone. We examined the electronic medical records of all 3,672 men evaluated for hypogonadism by a serum testosterone panel, including total testosterone, sex hormone-binding globulin, albumin and calculated free testosterone, from January 1, 1997 through December 31, 2007 in a network that serves veterans in Washington. The sensitivity and specificity of low total testosterone (less than 280 ng/dl) to rule out and predict low calculated free testosterone was 91.0% and 73.7%, respectively. At thresholds of less than 350 and less than 400 ng/dl the sensitivity of total testosterone for low calculated free testosterone increased to 96.8% and 98.2%, and at thresholds of less than 150 and less than 200 ng/dl specificity increased to 98.9% and 92.6%, respectively. Total testosterone between 280 and 350 ng/dl is not sensitive enough to reliably exclude hypogonadism. Total testosterone must exceed 350 to 400 ng/dl to reliably predict normal free testosterone. Except when levels are less than 150 ng/dl total testosterone measurement has low specificity for the biochemical diagnosis of hypogonadism. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Maximal Testosterone Suppression in Prostate Cancer—Free vs Total Testosterone

    OpenAIRE

    Rove, Kyle O.; Crawford, E. David; Perachino, Massimo; Morote, Juan; Klotz, Laurence; Lange, Paul H.; Andriole, Gerald L.; Matsumoto, Alvin M.; Taneja, Samir S.; Eisenberger, Mario A.; Reis, Leonardo O.

    2014-01-01

    Testosterone remains a key target in the treatment of advanced prostate cancer. The relationship of free testosterone to prostate cancer treatment and outcomes remains largely unexplored. A consensus of prostate cancer experts was convened in 2013 to review current knowledge surrounding relationship of total and free testosterone to prostate cancer, discuss the free hormone hypothesis, and highlight future avenues for therapeutics. Free testosterone may better reflect prostate cancer tissue a...

  8. Decreased Absorption of Dolutegravir and Tenofovir Disoproxil Fumarate, But Not Emtricitabine, in an HIV-Infected Patient Following Oral and Jejunostomy-Tube Administration.

    Science.gov (United States)

    Brooks, Kristina M; Garrett, Katy L; Kuriakose, Safia S; George, Jomy M; Balba, Gayle; Bailey, Bria; Anderson, Megan; Lane, H Clifford; Maldarelli, Frank; Pau, Alice K

    2017-08-01

    The use of enteral feeding tubes to administer antiretroviral medications is necessary in certain patients with human immunodeficiency virus (HIV) infection. However, adequacy of drug exposures after these administration routes are largely unknown, making dosing recommendations and the attainment of viral suppression challenging in this patient population. This report describes a patient with advanced HIV infection and a complicated medical history including long-term intractable nausea/vomiting necessitating antiretroviral medication administration via a Roux-en-Y jejunostomy (J)-tube. Pharmacokinetic assessments were performed to compare differences in antiretroviral drug absorption and plasma exposure following oral and J-tube administration of dolutegravir, tenofovir disoproxil fumarate, and emtricitabine. Results were also compared with published pharmacokinetic data in HIV-infected individuals. Exposure to dolutegravir and tenofovir were similar between J-tube and oral administration routes, whereas emtricitabine exposure was 38% lower when administered via J-tube. However, in comparison with reference data in HIV-infected individuals taking these medications orally, exposure to dolutegravir and tenofovir was 75-76% and 55-61% lower, respectively, following both routes of administration. Emtricitabine exposure was similar to and 71% higher than reference data following J-tube and oral administration, respectively. This report highlights the importance of performing pharmacokinetic assessments in patients with the potential for impaired drug absorption to ensure antiretroviral treatment success. © 2017 Pharmacotherapy Publications, Inc.

  9. Testosterone a female hormone : Testing the function and evolution of testosterone in female birds

    NARCIS (Netherlands)

    de Jong, Berber

    2013-01-01

    Hoewel testosteron vaak het mannelijk geslachtshormoon wordt genoemd produceren vrouwen van heel veel diersoorten ook testosteron, zij het veelal in mindere mate. Wat de functie van dit hormoon is in vrouwtjes is, in tegenstelling tot bij mannetjes, slecht onderzocht. Hebben vrouwtjes testosteron,

  10. 17β-estradiol and testosterone sorption in soil with and without poultry litter.

    Science.gov (United States)

    Bera, M; Radcliffe, D E; Cabrera, M L; Vencill, W K; Thompson, A; Hassan, S

    2011-01-01

    17β-estradiol and testosterone are naturally occurring steroids that co-occur in poultry litter. The effects of litter on sorption of these hormones to soil are not known. Sorption isotherms were developed for C-labeled testosterone and H-labeled estradiol in a Cecil sandy clay loam with and without poultry litter addition. The effect of applying the hormones alone (single-sorbate) or together (multisorbate) was also investigated. C-testosterone sorption in soil increased from 2 to 48 h and remained relatively constant thereafter. H-estradiol sorption in soil was relatively constant from 2 to 24 h and then decreased to 72 h. These differences may reflect transformation of the parent hormones to products with different solid-phase affinity. The maximum sorption coefficient () in soil for C-testosterone (20.2 mL g) was similar to that for H-estradiol (19.6 mL g) in single-sorbate experiments. When hormones were applied together, sorption of both hormones in soil decreased, but the C-testosterone (12.5 mL g) was nearly twice as large as the H-estradiol (7.4 mL g). We propose this resulted from competition between the hormones and their transformation products for sorption sites, with C-testosterone and its expected transformation product (androstenedione) being better competitors than H-estradiol and its expected transformation product (estrone). When poultry litter was mixed with soil, sorption increased for H-estradiol but decreased for C-testosterone. This may have been because poultry litter slowed the transformation of parent hormones. Our results show that poultry litter could have important effects on the mobility of estradiol and testosterone. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  11. Influence of paradoxical sleep deprivation and sleep recovery on testosterone level in rats of different ages.

    Science.gov (United States)

    Oh, Mi Mi; Kim, Jin Wook; Jin, Myeong Heon; Kim, Je Jong; Moon, Du Geon

    2012-03-01

    This study was performed to assess serum testosterone alterations induced by paradoxical sleep deprivation (PSD) and to verify their attenuation during sleep recovery (SR) based on different durations and ages. Wistar male rats aged 12 weeks for the younger group and 20 weeks for the elder group were randomly distributed into one of the following groups: a control group (cage and platform), 3-day SD, 5-day SD, 7-day SD, 1-day SR, 3-day SR and 5-day SR groups. For PSD, the modified multiple platform method was used to specifically limit rapid eye movement (REM) sleep. Differences in the testosterone and luteinizing hormone levels between the younger group and the elder group according to duration of PSD and SR recovery were analysed. Testosterone continued to fall during the sleep deprivation period in a time-dependent manner in both the younger (P=0.001, correlation coefficient r=-0.651) and elder groups (P=0.001, correlation coefficient r=-0.840). The elder group showed a significantly lower level of testosterone compared with the younger group after PSD. Upon SR after 3 days of PSD, the testosterone level continued to rise for 5 days after sleep recovery in the younger group (P=0.013), whereas testosterone concentrations failed to recover until day 5 in the elder group. PSD caused a more detrimental effect on serum testosterone in the elder group compared to the younger group with respect to decreases in luteinizing hormone (LH) levels. The replenishment of serum testosterone level was prohibited in the elder group suggesting that the effects of SD/SR may be age-dependent. The mechanism by which SD affects serum testosterone and how age may modify the process are still unclear.

  12. Evidence for a positive association between serum carnitine and free testosterone levels in uremic men with hemodialysis.

    Science.gov (United States)

    Sakai, Kazuko; Fukami, Kei; Yamagishi, Sho-Ichi; Kaida, Yusuke; Adachi, Takeki; Ando, Ryotaro; Manabe, Rie; Otsuka, Aki; Sugi, Kenzo; Ueda, Seiji; Okuda, Seiya

    2013-06-01

    Low free testosterone levels are associated with sexual dysfunction and an increased risk of cardiovascular disease in male hemodialysis patients. Carnitine deficiency is frequently observed in hemodialysis patients as well. However, the relationship between carnitine and testosterone levels remains unknown. In this study, we examined whether carnitine deficiency was independently associated with low free testosterone levels in male hemodialysis patients. Nineteen male hemodialysis patients underwent determinations of blood chemistries, including serum levels of free testosterone, carnitine, and pentosidine, one of the well-characterized advanced glycation end products. Mean free testosterone levels in hemodialysis patients were significantly lower than those in healthy controls (4.67±2.69 vs. 9.50±3.67 pg/mL, pfree testosterone values. Multiple stepwise regression analysis revealed that carnitine (p=0.001) and statin use (inversely, p=0.002) were the independent determinants of age-adjusted free testosterone levels in hemodialysis patients (r² =0.612). The present study gives the first evidence that decreased carnitine levels were independently associated with low free testosterone values in male hemodialysis patients. Our study suggests that decreased carnitine levels may be a novel therapeutic target for uremic men with hemodialysis.

  13. Reduction in 24-Hour Plasma Testosterone Levels in Subjects Who Showered 15 or 30 Minutes After Application of Testosterone Gel

    NARCIS (Netherlands)

    de Ronde, W.; Vogel, S.; Bui, H.N.; Heijboer, A.C.

    2011-01-01

    Study Objective. To investigate whether showering, to prevent the involuntary transfer of testosterone to others through skin contact, either 15 or 30 minutes after application of testosterone gel would significantly affect plasma testosterone levels. Design. Prospective 3-way crossover trial.

  14. Effects of In Vivo Testosterone Manipulation on Ovarian Morphology, Follicular Development, and Follicle Yolk Testosterone in the Homing Pigeon

    NARCIS (Netherlands)

    Goerlich, Vivian C.; Dijkstra, Cor; Groothuis, Ton G. G.

    2010-01-01

    To date, our understanding of the function of testosterone in female reproductive physiology is only marginal although there are indications that testosterone is involved in modulating follicular recruitment, growth, atresia, and ovulation. Studies elevating testosterone in breeding female birds

  15. Pengaruh Tepung Teripang Pasir (Holothuria Scabra Terhadap Perilaku Seksual dan Kadar Testosteron Darah Mencit (Mus musculus

    Directory of Open Access Journals (Sweden)

    Sarifah Nurjanah

    2009-09-01

    Full Text Available Sea cucumber is generally believed as a natural material that can be used as a tonic food to increase man vitality. The aim of this study was to investigate the effect of sandfish powder on sexual behavior and blood testosterone level of male mice. Method applied in the study was laboratory experimental method. Mature male mice were treated with administration of sandfish powder with three dosage rate of steroid content (10, 30 and 50 ìg/100 g body weight during 12 days, whereas for control treatment were without hormone administration and with the metil testosterone administration. Parameters that were investigated were kissing vagina and mounting for sexual behavior and the blood testosterone level of male mice. It was found that administration of sandfish powder significantly give effect on the number of kissing vagina and mounting compared to control. Administration of 10 ìg/100 g body weight on male mice showed the highest sexual behavior with 25 kissing vagina for and 6 mounting for 30 minutes. Moreover, administration of sandfish powder increased the testosterone level in the male mice blood. This may due to the steroid contained in sandfish powder and nutrition value that increase mice libido. The study proved that the sandfish powder has a potential as a nature aphrodisiac.

  16. Testosterone and alcoholic cirrhosis. Epidemiologic, pathophysiologic and therapeutic studies in men

    DEFF Research Database (Denmark)

    Gluud, C

    1988-01-01

    testosterone concentrations, but 20% have values above and 20% have values below the normal limits. The majority of patients have raised sex hormone binding globulin (SHBG) concentrations. This increase accounts for the supranormal plasma testosterone concentrations. With decreasing liver function, plasma...... as well. Oral testosterone treatment significantly reduces the prevalence of gynecomastia, but is without significant effects on liver biochemistry, morphology, haemodynamics, and function, general well being, sexual dysfunction and survival of alcoholic cirrhotic men. A pooled estimate of the mortality...... risk of cirrhotic patients treated with anabolic-androgenic steroids does not disclose any significant difference compared with placebo treatment (relative risk 0.98; 95% confidence limits 0.77-1.22). Seldom, but serious, side-effects of oral testosterone treatment can not be excluded....

  17. Pola Diurnal Metabolit Testosteron dan Kortisol di dalam Feses Owa Jawa (Hylobates moloch di Penangkaran

    Directory of Open Access Journals (Sweden)

    PUDJI ASTUTI

    2006-06-01

    Full Text Available The aims of this research were to determine diurnal patterns of testosterone and cortisol metabolites to predict the testis functional status. In this study, fecal testosterone and cortisol were quantified in 77 samples from three male Hylobates moloch during a course of three months period. These data showed that the highest concentration of fecal testosterone occured at 18.00-06.00 (23.61 ng/g dried feces, then declined gradually. The lowest concentration was in the evening (5.54 ng/g dried feces. Our tests showed that there was a decrease in the mean testosterone concentration from 06.00-10.00 to 10.00-14.00 to 14.00-18.00. For cortisol, the highest concentration occured at 06.00-10.00 (597.84 ng/g dried feces, then decline gradually in the evening (225.73 ng/g dried feces.

  18. Modulating testosterone pathway: a new strategy to tackle male skin aging?

    Directory of Open Access Journals (Sweden)

    Bernard P

    2012-09-01

    Full Text Available Philippe Bernard1, Thomas Scior2, Quoc Tuan Do11Greenpharma SAS, Orléans, France; 2Pharmacy Department, Benemerita Universidad Autonoma de Puebla, Puebla, MexicoAbstract: In men, the level of testosterone decreases with age. At the skin level, the result is observed as a decrease in density and in a lower elasticity. Identifying compounds that are able to increase the level of testosterone appears to be an attractive strategy to develop new antiaging bioactive ingredients for men. Reverse pharmacognosy was successfully applied to identify new natural compounds able to modulate testosterone levels. Among several in silico hits, honokiol was retained as a candidate as it has the greatest potential to become an active ingredient. This result was then validated in vitro on aromatase and 5-alpha-reductase type 1 and 2, which are two types of enzymes implicated in the degradation of free testosterone. Indeed, honokiol was identified as an inhibitor of aromatase, with a half-maximal inhibitory concentration (IC50 of about 50 µM. In addition, honokiol was shown to be an inhibitor of 5-alpha-reductase type 1, with an IC50 of about 75 µM. Taken together, these data indicate that honokiol modulates testosterone levels, and its structure has the potential to serve as a lead for future designs of highly selective inhibitors of 5-alpha-reductase type 1.Keywords: reverse pharmacognosy, honokiol, testosterone, man cosmetics, dermopharmacy

  19. Does exposure to testosterone significantly alter endogenous metabolism in the marine mussel Mytilus galloprovincialis?

    Science.gov (United States)

    Fernandes, Denise; Navarro, Juan Carlos; Riva, Consuelo; Bordonali, Silvia; Porte, Cinta

    2010-11-15

    Mussels (Mytilus galloprovincialis) were exposed to different concentrations of testosterone (T: 20, 200 and 2000ng/L) in a semi-static water regime (1-day dosing intervals) for up to 5 days in an attempt to see whether endogenous steroid levels and steroid metabolism were altered by exogenous exposure to testosterone. Whole tissue levels of total testosterone (free+esterified) sharply increased in a concentration-dependent manner, from 2ng/g in controls to 290ng/g in organisms exposed to the highest concentration. In contrast, levels of free testosterone were only significantly elevated at the high-exposure group (5-fold increase with respect to controls). Increased activity of palmitoyl-CoA:testosterone acyltransferase (ATAT) was detected in organisms exposed to the highest concentration of testosterone, while those exposed to low and medium concentrations showed significant alterations in their polyunsaturated fatty acid profiles. The obtained results suggest that esterification of the excess of T with fatty acids might act as a homeostatic mechanism to maintain endogenous levels of free T stable. Interestingly, a decrease in CYP3A-like activity was detected in T-exposed mussels together with a significant decrease in the metabolism of the androgen precursor androstenedione to dihydrotestosterone (5α-DHT). Overall, the work contributes to the better knowledge of androgen metabolism in mussels. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction.

    Science.gov (United States)

    Wang, Fengyue; Yang, Jing; Sun, Junfeng; Dong, Yanli; Zhao, Hong; Shi, Hui; Fu, Lu

    2015-05-01

    Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses. © 2015 Society for Endocrinology.

  1. Alfa-lipoic acid protects testosterone secretion pathway and sperm quality against 4-tert-octylphenol induced reproductive toxicity.

    Science.gov (United States)

    Othman, Azza I; El-Missiry, Mohamed A; Koriem, Khaled M; El-Sayed, Aml A

    2012-07-01

    The protective effect of α-lipoic acid (LA) (50 mg/kg bw) against 4-tert-octylphenol (OP) (50 mg/kg bw) induced reproductive toxicity in male rats was studied. LA was injected 1h prior to OP administration three times a week. OP caused significant increase in oxidative stress in hypothalamus and epididymal sperm, disturbed hormonal levels in serum, decreased sperm quality, increased DNA fragmentation and loss of 35 and 95 kDa proteins in sperm, as well as elevated proliferating index in testis. LA protected against oxidative stress through promoting the levels of glutathione and glutathione-S-transferase in hypothalamus and sperm. In addition, LA prevented the decrease in testosterone, dehydroepiandrosterone sulfate, 3β-hydroxysteroid dehydrogenase, and inhibited the elevations in sex-hormone-binding globulin levels and showed normal sperm quality. LA modulated proliferation of germ cell, protected against DNA fragmentation and maintained membrane protein organization in the sperm. In conclusion, LA normalized oxidative stress and protected testosterone synthesis pathway across hypothalamus-testicular axis and sperm quality indicating its defensive influence against OP-induced oxidative reproductive dysfunction in male rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Cardiovascular complications following chronic treatment with cocaine and testosterone in adolescent rats.

    Directory of Open Access Journals (Sweden)

    Sheila A Engi

    Full Text Available Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR, and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.

  3. Relationship between 22-kHz calls and testosterone in male rats.

    Science.gov (United States)

    Inagaki, Hideaki; Mori, Yuji

    2014-01-01

    Ultrasonic calls in rats induced by the presence of a predator, referred to as "22-kHz calls," are mainly emitted by socially dominant male rats. Testosterone levels are closely related to social dominance in male rats. In the present study, we investigated the relationship between the emission of stress-induced 22-kHz calls and circulating testosterone levels in male rats, using a combination of surgery (castration or sham operation) and chronic steroid administration (testosterone or cholesterol) to modify circulating testosterone levels. We also assessed the effects of androgen and/or estrogen receptor antagonists on the emission of 22-kHz calls in male rats. An air puff stimulus, known to reliably induce 22-kHz calls in rats, was used as a stressor. Castrated rats with cholesterol implants exhibited significantly fewer 22-kHz calls than rats that had received a sham operation and cholesterol implants, and there was no significant difference between castrated rats with testosterone implants and rats that had received a sham operation and cholesterol implants. Only male rats pretreated with a binary mixture of androgen and estrogen antagonists exhibited significantly fewer 22-kHz calls than controls. These results show that testosterone in male rats has a positive effect on the emission of stress-induced 22-kHz calls, and the calls may be regulated by the activation of both androgen and estrogen receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. "PRELIMINARY SCREENING FOR THE LEVELS OF TESTOSTERONE HORMONE IN THE MARKET MEAT IN TEHRAN "

    Directory of Open Access Journals (Sweden)

    M. R. Oveisi

    2007-06-01

    Full Text Available Many xenobiotic and natural compounds such as testosterone have been used and sometime misused to improve the growth of cattle and other livestock animals. In order to control the testosterone hormone residues in meat and to ensure the safety of Iranian consumers, a monitoring system must be put in place to address the concerns. The present study was undertaken to detect and quantify the levels of testosterone residue in the market meat. Cattle meat samples were collected randomly from the market in Tehran. A total of 120 samples of cattle meat were analyzed for the level of testosterone by Enzyme-linked immuno sorbent assay (ELISA method. The average experimental value of testosterone in cattle meat was 810.9 ng/kg. The average value of cattle meat testosterone was significantly upper than FDA (Food and Drug Administration allowable level but was in agreement with the values proposed by JESFA (Joint Expert Committee on Food Additives. So it seems that the present status of this anabolic hormone in market meat is not at risk but there is need to routinely monitor this chemical as a food quality control measure.

  5. Cardiovascular complications following chronic treatment with cocaine and testosterone in adolescent rats.

    Science.gov (United States)

    Engi, Sheila A; Cruz, Fábio C; Leão, Rodrigo M; Spolidorio, Luís C; Planeta, Cleopatra S; Crestani, Carlos C

    2014-01-01

    Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.

  6. Review Article: Practical Aspects of Testosterone Deficiency ...

    African Journals Online (AJOL)

    In this review we describe the clinical manifestations associated with testosterone deficiency in aging men, termed the testosterone deficiency syndrome (TDS). Since aging men suffer from multiple urological and andrological symptoms, TDS is an important medical condition to be suspected, recognized, clinically ...

  7. [Salivary testosterone and cognitive ability in children].

    Science.gov (United States)

    Ostatnikova, D; Dohnanyiova, M; Mataseje, A; Putz, Z; Laznibatova, J; Hajek, J

    2000-01-01

    There are suggestive data with indicate the link of testosterone levels with specific cognitive abilities in humans. As soon as during intrauterine development, testosterone is supposed to influence to organization of fetal specific brain structures. This influence is permanent and it is reflected in cognitive abilities during prepubetal period. In puberty, the testosterone level rapidly increases mainly in boys and it appears to influence the definitive development of cognitive functions. In this paper, results of the first four years of our logitudinal study are presented. Salivary testosterone levels in children were determined, and their effect on spatial ability was studied. Radioimmunoanalytical method of testosterone determination in saliva was developed, since saliva reflects free fraction of testosterone directly available for uptake by receptors in the central nervous system. The sampling of saliva is non-invasive and unstressful, which is important for relevant evaluation of cognitive performance. One hundred and forty-seven children (78 boys and 69 girls) at the ae of 8 to 12 were examined. The data received from intellectually gifted children attending the School for gifted children in Bratislava (100 measurements) were compared with the data received from age-matched children attending randomly chosen elementary schools (151 measurements). Lower salivary testosterone levels were found in intellectually gifted children of both sexes, and negative relationship between testosterone levels and cognitive abilities in preadolescent children was observed.

  8. Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

    Science.gov (United States)

    Eriksson, C J P; Etelälahti, T J; Apter, S J

    2017-06-01

    A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational

  9. Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway.

    Science.gov (United States)

    Chen, Yan-qing; Zhao, Jing; Jin, Cheng-wei; Li, Yi-hui; Tang, Meng-xiong; Wang, Zhi-hao; Zhang, Wei; Zhang, Yun; Li, Li; Zhong, Ming

    2016-06-01

    Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.

  10. Testosterone-induced modulation of nitric oxide-cGMP signaling pathway and androgenesis in the rat Leydig cells.

    Science.gov (United States)

    Andric, Silvana A; Janjic, Marija M; Stojkov, Natasa J; Kostic, Tatjana S

    2010-09-01

    Testosterone, acting as a systemic and local factor, is one of the major regulatory molecules that initiate and maintain testicular function. In the present study, different experimental approaches were used to evaluate the role of testosterone in regulation of the nitric oxide (NO)-cGMP pathway in Leydig cells derived from normal and hypogonadotropic male rats treated with testosterone for 24 h and 2 wk. Real-time quantitative PCR and Western blot analysis revealed increased inducible NO synthase (NOS2) expression followed by increased NO secretion from Leydig cells ex vivo after continuous treatment with testosterone for 2 wk in vivo. The cGMP-specific phosphodiesterases Pde5, Pde6, and Pde9 were up-regulated, whereas PRKG1 protein was decreased after a 2-wk testosterone treatment. Induction of Nos2 and Pde5 in Leydig cells was blocked by androgen receptor antagonist. In experimental hypogonadotropic hypogonadism, expression of NOS2 was significantly reduced, and treatment with testosterone increased NOS2 expression above control levels. PDE5 protein level was unchanged in hypogonadal rats, whereas treatment of hypogonadal rats with testosterone significantly increased it. In contrast, hypogonadism and testosterone replacement reduced PRKG1 protein in Leydig cells. In vitro treatment with testosterone caused gradually increased Nos2 gene expression followed by increased nitrite and cGMP production by purified Leydig cells. In summary, testosterone up-regulated NO signaling via increased NOS2 expression and contributed to down-regulation of cGMP signaling in Leydig cells. Thus, testosterone-induced modulation of NO-cGMP signaling may serve as a potent autocrine regulator of testicular steroidogenesis.

  11. Effects of testosterone and estradiol on anxiety and depressive-like behavior via a non-genomic pathway.

    Science.gov (United States)

    Filova, Barbora; Malinova, Maria; Babickova, Janka; Tothova, Lubomira; Ostatnikova, Daniela; Celec, Peter; Hodosy, Julius

    2015-06-01

    Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genomic pathway of testosterone and estradiol in the amygdala in relation to anxiety and depressive-like behavior. Sham-operated and gonadectomized male rats (GDX) supplemented with testosterone propionate, estradiol, or olive oil were used. Five minutes after administration, anxiety and depression-like behavior were tested. Estradiol increased anxiolytic behavior in the open-field test compared to the GDX group, but administration of testosterone had no significant effect. Besides, c-Fos expression in the medial nucleus of the amygdala significantly increased after testosterone treatment compared to the GDX group, while no significant difference was observed in the central and the basolateral nuclei of the amygdala in the testosterone-treated group compared to the GDX group. In conclusion, estradiol had an anxiolytic effect via a rapid pathway, but no rapid effect of testosterone on anxiety was found. Further studies elucidating whether the rapid effect is mediated by a non-genomic pathway are needed.

  12. Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

    Science.gov (United States)

    Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

    2017-01-01

    The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Testosterone Replacement Therapy and the Cardiovascular System.

    Science.gov (United States)

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  14. Live birth of twins after performing early hCG administration as a modification of natural cycle in vitro fertilization, in a women with decreased ovarian reserve.

    Science.gov (United States)

    Hyman, Jordana H; Sokal-Arnon, Tamar; Son, Weon-Young; Tan, Seang Lin; Dahan, Michael H

    2015-01-01

    This case reports the first twin live births achieved in a woman with a serum FSH of such magnitude -80 IU/L, after following early hCG administration in natural cycle in vitro fertilization (IVF). Case report. A 27-year-old with 2 years of primary infertility presented with regular menses since menarche. FSH following clomiphene citrate challenge test was 80 IU/L. Antral follicle count was 1. After failing two IVF cycles, natural cycle IVF with early hCG administration was attempted. Ovulation with 10,000 IU hCG was triggered when the dominant follicle was 10 mm in mean diameter. Two smaller follicles were also present. Oocyte collection was performed 38 h after hCG injection. Three mature oocytes were retrieved. Two oocytes fertilized normally. Two good-quality embryos were transferred on day 2. Bichorionic biamniotic pregnancy was achieved and healthy twins were delivered at term. This case suggests that natural cycles with early hCG administration should be investigated further as an option for poor responders to retrieve more than one mature oocyte, and prevent premature ovulation. We believe this case to represent the patient with the highest serum FSH level, reflective of ovarian reserve at the time of treatment, to achieve a live birth. It is also the first case report to describe this modification on the traditional natural cycle.

  15. Salivary Testosterone Levels Under Psychological Stress and Its Relationship with Rumination and Five Personality Traits in Medical Students

    Science.gov (United States)

    Afrisham, Reza; Sadegh-Nejadi, Sahar; SoliemaniFar, Omid; Kooti, Wesam; Ashtary-Larky, Damoon; Alamiri, Fatima; Najjar-Asl, Sedigheh; Khaneh-Keshi, Ali

    2016-01-01

    Objective The purpose of this study was to evaluate the salivary testosterone levels under psychological stress and its relationship with rumination and five personality traits in medical students. Methods A total of 58 medical students, who wanted to participate in the final exam, were selected by simple random sampling. Two months before the exam, in the basal conditions, the NEO Inventory short form, and the Emotional Control Questionnaire (ECQ) were completed. Saliva samples were taken from students in both the basal conditions and under exam stress. Salivary testosterone was measured by ELISA. Data was analyzed using multivariate analysis of variance with repeated measures, paired samples t-test, Pearson correlation and stepwise regression analysis. Results Salivary testosterone level of men showed a significant increase under exam stress (pstress. Conclusion Salivary testosterone reactivity to stress can be determined by sexual differences, personality traits, and emotional control variables which may decrease or increase stress effects on biological responses, especially the salivary testosterone. PMID:27909455

  16. Salivary Testosterone Levels Under Psychological Stress and Its Relationship with Rumination and Five Personality Traits in Medical Students.

    Science.gov (United States)

    Afrisham, Reza; Sadegh-Nejadi, Sahar; SoliemaniFar, Omid; Kooti, Wesam; Ashtary-Larky, Damoon; Alamiri, Fatima; Aberomand, Mohammad; Najjar-Asl, Sedigheh; Khaneh-Keshi, Ali

    2016-11-01

    The purpose of this study was to evaluate the salivary testosterone levels under psychological stress and its relationship with rumination and five personality traits in medical students. A total of 58 medical students, who wanted to participate in the final exam, were selected by simple random sampling. Two months before the exam, in the basal conditions, the NEO Inventory short form, and the Emotional Control Questionnaire (ECQ) were completed. Saliva samples were taken from students in both the basal conditions and under exam stress. Salivary testosterone was measured by ELISA. Data was analyzed using multivariate analysis of variance with repeated measures, paired samples t-test, Pearson correlation and stepwise regression analysis. Salivary testosterone level of men showed a significant increase under exam stress (pstress. Salivary testosterone reactivity to stress can be determined by sexual differences, personality traits, and emotional control variables which may decrease or increase stress effects on biological responses, especially the salivary testosterone.

  17. Effect of testosterone deficiency on cholesterol metabolism in pigs fed a high-fat and high-cholesterol diet.

    Science.gov (United States)

    Cai, Zhaowei; Xi, Haitao; Pan, Yongming; Jiang, Xiaoling; Chen, Liang; Cai, Yueqin; Zhu, Keyan; Chen, Cheng; Xu, Xiaoping; Chen, Minli

    2015-03-07

    Testosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet. Sexually mature male miniature pigs (6-7 months old) were randomly divided into 3 groups as follows: intact male pigs fed an HFC diet (IM+HFC), castrated male pigs fed an HFC diet (CM+HFC), and castrated pigs with testosterone replacement fed an HFC diet (CM+HFC+T). Serum testosterone levels and lipid profiles were measured, and gene expression levels associated with hepatic cholesterol metabolism were determined. Furthermore, total hepatic cholesterol contents and the activities of enzymes mediating hepatic cholesterol metabolism were measured. Serum testosterone levels were significantly decreased in CM+HFC pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. Castration significantly increased the serum levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as hepatic lipid contents in pigs fed an HFC diet. Compared with IM+HFC and CM+HFC+T pigs, low-density lipoprotein receptor (LDLR) mRNA expression and protein levels were significantly decreased in the livers of CM+HFC pigs. In contrast, we found that compared with IM+HFC pigs, hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and serum PCSK9 protein levels were significantly increased in CM+HFC pigs. Moreover, testosterone treatment reversed the increase in PCSK9 expression in CM+HFC pigs. However, neither castration nor testosterone replacement affected the expression of the other hepatic genes that were tested. This study demonstrated that castration-induced testosterone deficiency caused severe hypercholesterolemia in pigs fed an HFC diet; furthermore, these

  18. Cortisol, testosterone and mood state variation during an official female football competition.

    Science.gov (United States)

    Casanova, Natalina; Palmeira-DE-Oliveira, Ana; Pereira, Ana; Crisóstomo, Luís; Travassos, Bruno; Costa, Aldo M

    2016-06-01

    Endogenous hormones are essential on the control of physiological reactions and adaptations during sport performance. This study aims to compare the mood state and the salivary levels of cortisol and testosterone during an official female association football tournament. Twenty female football players (22.85±4.2 years) from the Portuguese women's national team were included in the study. Mood, salivary cortisol and testosterone levels were examined in five moments over the championship (M1, neutral measures; M2-M5, on every match day). Saliva samples were collected before breakfast and immediately after each match. Mood was measured by the profile of mood states questionnaire (POMS); hormone levels were measure by immunoassay methods. Iceberg Profiles of POMS were observed during all the moments of evaluation (M2-M5), showing a decrease in vigor and an increase in tension and depression in both team defeats (M2 and M5). There is no relationship between the hormones levels and the outcome of the competition, once cortisol and testosterone decrease from pre-match to post-match in both wins (M2 and M5) and defeats (M3 and M4). For testosterone the observed decrease is significantly different (Pmood states behavior. Cortisol and testosterone decrease after match and throughout the tournament, independently of the match outcome. The absence of hormone fluctuations related to competition performance points out that top-level professional football players training systematically and regularly seem to be very well adapted to competition stress effect.

  19. Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

    Science.gov (United States)

    Tirabassi, G; delli Muti, N; Gioia, A; Biagioli, A; Lenzi, A; Balercia, G

    2014-04-01

    The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

  20. Testosterone and cortisol jointly regulate dominance: evidence for a dual-hormone hypothesis.

    Science.gov (United States)

    Mehta, Pranjal H; Josephs, Robert A

    2010-11-01

    Traditional theories propose that testosterone should increase dominance and other status-seeking behaviors, but empirical support has been inconsistent. The present research tested the hypothesis that testosterone's effect on dominance depends on cortisol, a glucocorticoid hormone implicated in psychological stress and social avoidance. In the domains of leadership (Study 1, mixed-sex sample) and competition (Study 2, male-only sample), testosterone was positively related to dominance, but only in individuals with low cortisol. In individuals with high cortisol, the relation between testosterone and dominance was blocked (Study 1) or reversed (Study 2). Study 2 further showed that these hormonal effects on dominance were especially likely to occur after social threat (social defeat). The present studies provide the first empirical support for the claim that the neuroendocrine reproductive (HPG) and stress (HPA) axes interact to regulate dominance. Because dominance is related to gaining and maintaining high status positions in social hierarchies, the findings suggest that only when cortisol is low should higher testosterone encourage higher status. When cortisol is high, higher testosterone may actually decrease dominance and in turn motivate lower status. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response.

    Science.gov (United States)

    White, Hillary D; Brown, Lin A J; Gyurik, Robert J; Manganiello, Paul D; Robinson, Thomas D; Hallock, Linda S; Lewis, Lionel D; Yeo, Kiang-Teck J

    2015-08-01

    To test our hypothesis that testosterone deficiency plays an important role in chronic pain, a Phase I/II pilot study was initiated with 12 fibromyalgia patients to verify that a daily dose for 28days with transdermal testosterone gel would 1) significantly and safely increase mean serum testosterone concentrations from low baseline levels to mid/high-normal levels, and 2) effectively treat the pain and fatigue symptoms of fibromyalgia. Pharmacokinetic data confirmed that serum free testosterone concentrations were raised significantly above baseline levels, by assessment of maximum hormone concentration (Cmax) and area under the curve (AUC) parameters: free testosterone Cmax was significantly raised from a mean of 2.64pg/mL to 3.91pg/mL (pfibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment. These results are consistent with the hypothesized ability of testosterone to relieve the symptoms of fibromyalgia. Symptoms not tightly related to fibromyalgia were not improved. Copyright © 2015. Published by Elsevier B.V.

  2. Endogenous testosterone, muscle strength, and fat-free mass in men with chronic kidney disease.

    Science.gov (United States)

    Cigarrán, Secundino; Pousa, Montserrat; Castro, María Jesús; González, Berta; Martínez, Aurelia; Barril, Guillermina; Aguilera, Abelardo; Coronel, Francisco; Stenvinkel, Peter; Carrero, Juan Jesús

    2013-09-01

    Testosterone deficiency is a common finding in men with chronic kidney disease (CKD). Testosterone is thought to play an important anabolic role in muscle synthesis, and muscle wasting is an important and deleterious characteristic of protein-energy wasting (PEW) in CKD. It is presently unknown if reduced endogenous testosterone associates with features of muscle wasting in men with CKD. This was a cross-sectional observational study of 267 men with CKD stages 2-4 (mean ± standard deviation age 67 ± 13 years, estimated glomerular filtration rate 42.9 [interquartile range 30.2-56.7] mL/min/1.73 m²) with measurements of endogenous testosterone and surrogates of PEW such as albumin, prealbumin, high-sensitivity C-reactive protein (CRP) and normalized protein nitrogen appearance (nPNA). Fat-free mass was estimated by bioelectrical impedance vector analysis (BIVA) and muscle strength by handgrip dynamometry. Across decreasing thirds of testosterone distribution, patients were incrementally older and CRP levels rose significantly. Prealbumin, hemoglobin, nPNA, handgrip strength, and BIVA estimated surrogates of muscle mass and nutritional status (fat-free mass, body cell mass, and phase angle) were progressively reduced (P testosterone significantly and independently contributed to explain the variances of handgrip strength and fat-free mass (P testosterone independently associates with muscle strength and fat-free mass in men with moderate CKD. It is plausible that the reduction in testosterone levels that accompanies CKD may further contribute to the procatabolic environment leading to muscle wasting. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  3. Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

    Science.gov (United States)

    Soljancic, Andrea; Ruiz, Arnaldo Lopez; Chandrashekar, Kiran; Maranon, Rodrigo; Liu, Ruisheng; Juncos, Luis A.

    2013-01-01

    Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol. PMID:23552495

  4. Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men.

    Science.gov (United States)

    Atkinson, Ross A; Srinivas-Shankar, U; Roberts, Stephen A; Connolly, Martin J; Adams, Judith E; Oldham, Jackie A; Wu, Frederick C W; Seynnes, Olivier R; Stewart, Claire E H; Maganaris, Constantinos N; Narici, Marco V

    2010-11-01

    Testosterone increases lean mass and may help to counter the changes in muscle architecture associated with sarcopenia. This study was designed to investigate the effects of testosterone replacement therapy on skeletal muscle architecture in intermediate-frail and frail elderly men. A subgroup of 30 intermediate-frail and frail elderly men (65-89 years) with low to borderline-low testosterone levels were enrolled from a single-center randomized, double-blind placebo-controlled trial. Participants received either a transdermal testosterone (50 mg) or placebo gel daily for 6 months. Architecture (muscle thickness, fascicle length, and pennation angle) of the gastrocnemius medialis muscle was assessed by ultrasound imaging at baseline and after 6 months of treatment. Serum testosterone increased from 11.6 ± 3.5 to 18.0 ± 8.1 nmol/L by 10 days after randomization in the active group (but not the placebo group) and was maintained throughout the treatment period. Testosterone treatment resulted in a preservation of muscle thickness at 6 months while it decreased in the placebo group (effect size 1.4 [95% confidence interval = 0.3-2.5; p = .015]). There was no significant effect of treatment on fascicle length (effect size 1.9 mm [95% confidence interval = -1.2 to 5.0 mm; p = .22]) or pennation angle (effect size 1.2° [95% confidence interval = -1.3 to 3.7°; p = .32]). Testosterone replacement in intermediate-frail and frail elderly men is associated with preservation of muscle thickness. The results suggest that testosterone mitigates sarcopenia by improving muscle tissue to maintain a state of normality in aging men.

  5. Marital sex frequency and midcycle female testosterone.

    Science.gov (United States)

    Morris, N M; Udry, J R; Khan-Dawood, F; Dawood, M Y

    1987-02-01

    The purpose of the study was to attempt to replicate a finding of Persky et al. (1978) that midcycle peak values of testosterone (T) in women predicted differences in frequency of intercourse among married couples. Luteinizing hormone (LH), total testosterone (TT), and free testosterone (FT) values from 10 to 14 daily midcycle blood samples donated by 43 volunteering wives were analyzed against sexual activity patterns reported by the couples over a longer period of time. All couples were contracepting by means other than exogenous hormones or the rhythm method. Each morning through three menstrual cycles husbands and wives recorded independently and on separate forms answers to a series of questions concerning sexual activity in the previous 24 hr. Wives also recorded basal body temperatures (BBT). We designated midcycle values of TT and FT according to several definitions of midcycle. Total testosterone levels at the day of the BBT nadir and the day before the nadir correlated significantly with average intercourse frequency. Correlations with FT were statistically significant regardless of which midcycle measure was used; the day before the BBT nadir gave the highest correlation, 0.618, p = 0.01. Mean testosterone (TT or FT) values were not significantly related. We conclude that female midcycle total testosterone or free testosterone is indexing some unobserved event that affects the frequency of intercourse of couples. We speculate that this event affects the motivation of females, which influences the set point of the compromise frequency characteristic of couples.

  6. Testosterone and cardiovascular disease in men

    Science.gov (United States)

    Morris, Paul D; Channer, Kevin S

    2012-01-01

    Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ‘Perspectives' article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ‘cause' versus ‘effect' controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease. PMID:22522504

  7. Systemic administration of two different anxiolytic drugs decreases local field potential theta frequency in the medial entorhinal cortex without affecting grid cell firing fields.

    Science.gov (United States)

    Monaghan, Caitlin K; Chapman, G William; Hasselmo, Michael E

    2017-11-19

    Neurons coding spatial location (grid cells) are found in medial entorhinal cortex (MEC) and demonstrate increasing size of firing fields and spacing between fields (grid scale) along the dorsoventral axis. This change in grid scale correlates with differences in theta frequency, a 6-10Hz rhythm in the local field potential (LFP) and rhythmic firing of cells. A relationship between theta frequency and grid scale can be found when examining grid cells recorded in different locations along the dorsoventral axis of MEC. When describing the relationship between theta frequency and grid scale, it is important to account for the strong positive correlation between theta frequency and running speed. Plotting LFP theta frequency across running speeds dissociates two components of this relationship: slope and intercept of the linear fit. Change in theta frequency through a change in the slope component has been modeled and shown experimentally to affect grid scale, but the prediction that change in the intercept component would not affect grid scale has not been tested experimentally. This prediction about the relationship of intercept to grid scale is the primary hypothesis tested in the experiments presented here. All known anxiolytic drugs decrease hippocampal theta frequency despite their differing mechanisms of action. Specifically, anxiolytics decrease the intercept of the theta frequency-running speed relationship in the hippocampus. Here we demonstrate that anxiolytics decrease the intercept of the theta frequency-running speed relationship in the MEC, similar to hippocampus, and the decrease in frequency through this change in intercept does not affect grid scale. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Re: Could Testosterone Replacement Therapy in Hypogonadal Men Ameliorate Anemia, a Cardiovascular Risk Factor? An Observational, 54-week Cumulative Registry Study

    Directory of Open Access Journals (Sweden)

    Emre Bakırcıoğlu

    2016-09-01

    Full Text Available Testosterone deficiency syndrome may associate with erectile dysfunction, increased abdominal fat and reduced muscle mass. Low serum testosterone is also related with anemia, metabolic syndrome and cardiovascular disease. In this study, the authors investigated if testosterone undecanoate (TU reduces anemia and the risk of cardiovascular disease in patients with hypogonadism A total of 58 participants with a total testosterone level of less than 2.35 ng/ml received an injection of 1.000 mg TU 6 times; at initial visit, 6, 18, 30, 42 and 54 weeks. They observed that total testosterone and free testosterone levels were restored by TU. Hemoglobin and hematocrit levels significantly increased while anemia and total cholesterol levels significantly reduced. Although there are some limitations of this study e.g. it is not a randomized controlled and a long-term study, TU treatment in hypogonadal men decreased the prevalence of anemia, improved lipid profiles and lowered the risk of cardiovascular disease.

  9. Testosterone Regulates NUCB2 mRNA Expression in Male Mouse Hypothalamus and Pituitary Gland.

    Science.gov (United States)

    Seon, Sojeong; Jeon, Daun; Kim, Heejeong; Chung, Yiwa; Choi, Narae; Yang, Hyunwon

    2017-03-01

    Nesfatin-1/NUCB2 is known to take part in the control of the appetite and energy metabolism. Recently, many reports have shown nesfatin-1/NUCB2 expression and function in various organs. We previously demonstrated that nesfatin-1/NUCB2 expression level is higher in the pituitary gland compared to other organs and its expression is regulated by 17β-estradiol and progesterone secreted from the ovary. However, currently no data exist on the expression of nesfatin-1/NUCB2 and its regulation mechanism in the pituitary of male mouse. Therefore, we examined whether nesfatin-1/NUCB2 is expressed in the male mouse pituitary and if its expression is regulated by testosterone. As a result of PCR and western blotting, we found that a large amount of nesfatin-1/NUCB2 was expressed in the pituitary and hypothalamus. The NUCB2 mRNA expression level in the pituitary was decreased after castration, but not in the hypothalamus. In addition, its mRNA expression level in the pituitary was increased after testosterone treatment in the castrated mice, whereas, the expression level in the hypothalamus was significantly decreased after the treatment with testosterone. The in vitro experiment to elucidate the direct effect of testosterone on NUCB2 mRNA expression showed that NUCB2 mRNA expression was significantly decreased with testosterone in cultured hypothalamus tissue, but increased with testosterone in cultured pituitary gland. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the male mouse pituitary and was regulated by testosterone. This data suggests that reproductive-endocrine regulation through hypothalamus-pituitary-testis axis may contribute to NUCB2 mRNA expression in the mouse hypothalamus and pituitary gland.

  10. Decreased oxidative stress and greater bone anabolism in the aged, when compared to the young, murine skeleton with parathyroid hormone administration.

    Science.gov (United States)

    Jilka, Robert L; Almeida, Maria; Ambrogini, Elena; Han, Li; Roberson, Paula K; Weinstein, Robert S; Manolagas, Starros C

    2010-10-01

    Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. Parathyroid hormone produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26- when compared to 6 -month-old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae, and the toughness of both vertebrae and femora in old, but not young, mice. Parathyroid hormone also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species, p66(Shc) phosphorylation, and expression of the lipoxygenase Alox15, and it increased glutathione and stimulated Wnt signaling in bone of old mice. Parathyroid hormone also antagonized the effects of oxidative stress on p66(Shc) phosphorylation, Forkhead Box O transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N-acetyl cysteine or pegylated catalase reduced osteoblast progenitors and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation, it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling. © 2010 Blackwell Munksgaard No claim to original US government works.

  11. Testosterone and aggressive behavior in man.

    Science.gov (United States)

    Batrinos, Menelaos L

    2012-01-01

    Atavistic residues of aggressive behavior prevailing in animal life, determined by testosterone, remain attenuated in man and suppressed through familial and social inhibitions. However, it still manifests itself in various intensities and forms from; thoughts, anger, verbal aggressiveness, competition, dominance behavior, to physical violence. Testosterone plays a significant role in the arousal of these behavioral manifestations in the brain centers involved in aggression and on the development of the muscular system that enables their realization. There is evidence that testosterone levels are higher in individuals with aggressive behavior, such as prisoners who have committed violent crimes. Several field studies have also shown that testosterone levels increase during the aggressive phases of sports games. In more sensitive laboratory paradigms, it has been observed that participant's testosterone rises in the winners of; competitions, dominance trials or in confrontations with factitious opponents. Aggressive behavior arises in the brain through interplay between subcortical structures in the amygdala and the hypothalamus in which emotions are born and the prefrontal cognitive centers where emotions are perceived and controlled. The action of testosterone on the brain begins in the embryonic stage. Earlier in development at the DNA level, the number of CAG repeats in the androgen receptor gene seems to play a role in the expression of aggressive behavior. Neuroimaging techniques in adult males have shown that testosterone activates the amygdala enhancing its emotional activity and its resistance to prefrontal restraining control. This effect is opposed by the action of cortisol which facilitates prefrontal area cognitive control on impulsive tendencies aroused in the subcortical structures. The degree of impulsivity is regulated by serotonin inhibiting receptors, and with the intervention of this neurotransmitter the major agents of the neuroendocrine

  12. Incidence of dye coupling among magnocellular paraventricular nucleus neurons in male rats is testosterone dependent.

    Science.gov (United States)

    Cobbett, P; Yang, Q Z; Hatton, G I

    1987-03-01

    Recently published work in the rat has shown that: the incidence of electrical coupling, as measured by dye coupling, is decreased from control levels by 8 days of drinking hypertonic saline; an index of circulating testosterone, seminal vesicle weight, is also decreased by 8 days of saline drinking; and both plasma and urinary vasopressin levels are reduced in castrated males, but can be returned to normal with testosterone replacement. These findings have led to the hypothesis that dye coupling, particularly that involving vasopressinergic cells, may be affected by gonadal steroids. We have investigated the effects of castration and testosterone replacement on the incidence of dye coupling among the neurons of the predominantly vasopressinergic magnocellular lateral paraventricular nucleus in slices of male rat hypothalamus. Incidence of dye coupling in this nucleus of castrated rats was found to be decreased by 67% from sham castrated control levels. Testosterone-filled Silastic capsules (but not empty capsules) implanted subcutaneously at the time of castration abolished the effect of castration on dye coupling. We conclude that testosterone has a powerful influence upon coupling among PVN vasopressinergic neurons and may participate in the control of vasopressin release in intact animals.

  13. Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes

    Science.gov (United States)

    Dhindsa, Sandeep; Ghanim, Husam; Batra, Manav; Kuhadiya, Nitesh D.; Abuaysheh, Sanaa; Sandhu, Sartaj; Green, Kelly; Makdissi, Antoine; Hejna, Jeanne; Chaudhuri, Ajay; Punyanitya, Mark

    2016-01-01

    OBJECTIVE One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (−3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat. PMID:26622051

  14. Co-administration of paroxetine increased the systemic exposure of pravastatin in diabetic rats due to the decrease in liver distribution.

    Science.gov (United States)

    Li, Feng; Xu, Dan; Shu, Nan; Zhong, Zeyu; Zhang, Mian; Liu, Can; Ling, Zhaoli; Liu, Li; Liu, Xiaodong

    2015-01-01

    1. Liver distribution and systemic exposure of pravastatin were the determinant factors of efficacy and toxicity of pravastatin. Aim of the present study was to investigate the effect of paroxetine on the liver distribution and systemic exposure of pravastatin in diabetic rats induced by combining high fat diet (HFD) and low-dose streptozotocin (STZ). 2. Plasma concentrations and liver distribution of pravastatin were measured in the presence of paroxetine. Effect of paroxetine on pravastatin excretion via bile, intestine, feces and urine, as well as pravastatin absorption via intestine was documented. Freshly isolated hepatocytes and Caco-2 cells were used to investigate the effect of paroxetine on pravastatin transport. 3. Paroxetine increased the systemic exposure of pravastatin and decreased hepatic distribution of pravastatin in diabetic rats. In vitro, paroxetine inhibited the hepatic uptake of pravastatin and promoted the efflux of pravastatin in freshly isolated hepatocytes, which may partly explain the decreased hepatic distribution of pravastatin by paroxetine. It was also observed that paroxetine promoted the absorption of pravastatin via jejunum and the uptake of pravastatin in Caco-2 cells. 4. We concluded that paroxetine increased the systemic exposure of pravastatin partly via promoting absorption via jejunum and inhibiting hepatic uptake of pravastatin.

  15. Central administration of ghrelin and agouti-related protein (83-132) increases food intake and decreases spontaneous locomotor activity in rats.

    Science.gov (United States)

    Tang-Christensen, Mads; Vrang, Niels; Ortmann, Sylvia; Bidlingmaier, Martin; Horvath, Tamas L; Tschöp, Matthias

    2004-10-01

    Ghrelin was recently identified as an endogenous ligand of the GH secretagogue receptor. The novel peptide hormone is produced by gastric A-like cells, and circulating levels rise before feeding, suggestive of ghrelin as an endogenous hunger factor. ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AGRP). To examine whether ghrelin-induced feeding resembles NPY and AGRP [AGRP fragment (83-132)] induced orexia, we compared the short- and long-term orexigenic capacity of the three peptides. A single intracerebroventricular injection of ghrelin (0.2, 1.0, and 5.0 microg) increased food intake in a dose-dependent manner. A prolonged and uncompensated increase in feeding was seen after the highest dose of ghrelin. The prolonged effects on feeding (+72 h) closely resembled those of AGRP (83-132) but not NPY. Surprisingly, ghrelin injections reduced overall locomotor activity by 20% during the first 24-h observation period. AGRP (83-132) had similar effects on locomotor behavior, whereas NPY had no effect. In summary, ghrelin causes long-term increases of food intake and, like AGRP, plays a previously unknown role as a suppressor of spontaneous physical activity. Expanding the current model of food intake control to include mechanisms regulating physical activity may promote our understanding of two major etiological factors causing obesity.

  16. Non-classical actions of testosterone and spermatogenesis

    OpenAIRE

    Walker, William H.

    2010-01-01

    Testosterone is essential to maintain spermatogenesis and male fertility. In the absence of testosterone stimulation, spermatogenesis does not proceed beyond the meiosis stage. After withdrawal of testosterone, germ cells that have progressed beyond meiosis detach from supporting Sertoli cells and die, whereas mature sperm cannot be released from Sertoli cells resulting in infertility. The classical mechanism of testosterone action in which testosterone activates gene transcription by causing...

  17. The relationship between health-related quality of life, obesity and testosterone levels in older men

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Nielsen, Torben Leo; Wraae, Kristian

    2014-01-01

    quality of life evaluated by Short-Form 36 (SF-36) is decreased in obesity and hypogonadism, but the importance of regional fat mass is unknown. In the present study, we evaluated associations between SF-36, regional fat deposits and bioavailable testosterone (BioT) in ageing men.......quality of life evaluated by Short-Form 36 (SF-36) is decreased in obesity and hypogonadism, but the importance of regional fat mass is unknown. In the present study, we evaluated associations between SF-36, regional fat deposits and bioavailable testosterone (BioT) in ageing men....

  18. Effect of Voluntary Ethanol Consumption Combined with Testosterone Treatment on Cardiovascular Function in Rats: Influence of Exercise Training.

    Science.gov (United States)

    Engi, Sheila A; Planeta, Cleopatra S; Crestani, Carlos C

    2016-01-01

    This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6), animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α1-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances.

  19. Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats.

    Science.gov (United States)

    Mahesh, Malleswarapu; Bharathi, Munugala; Reddy, Mooli Raja Gopal; Kumar, Manchiryala Sravan; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

  20. Neonatal administration of N-omega-nitro-L-arginine induces permanent decrease in NO levels and hyperresponsiveness to locomotor activity by D-amphetamine in postpubertal rats.

    Science.gov (United States)

    Morales-Medina, Julio César; Mejorada, Alejandro; Romero-Curiel, Alejandra; Aguilar-Alonso, Patricia; León-Chávez, Bertha Alicia; Gamboa, Citlalli; Quirion, Remi; Flores, Gonzalo

    2008-12-01

    Nitric oxide (NO) is associated with dopamine (DA) release. Previously, we demonstrated that rats treated with a non-selective nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (L-NNA) at postnatal days 4-6 (PD4-6) show increased locomotion and disrupt neuronal cytoarchitecture after puberty (PD60). Here, we investigate whether the modulation of NO production in rats at PD4-6 causes long term changes of NO system, its impact on DA innervation, and schizophrenia-like behaviors. NO levels were measured in seven brain areas at PD35, PD60, PD90, and PD120. Autoradiographic studies explored the effect of l-NNA on the expression of D1 and D2 receptors in the caudate-putamen (CPu) and nucleus accumbens (NAcc) at PD60. Locomotor activity was assessed at PD60 using the non-selective DA agonists, amphetamine and apomorphine, and the selective DA receptor agonist [D2, quinpirole; D3, 7-hydroxy-N,N-di-n-propylaminotetralin ((+/-)-7-OH-DPAT)]. L-NNA treatment produced decreases in NO levels in the frontal cortex, striatum, brainstem and cerebellum, while in the occipital cortex changes were observed at PD120. Hippocampus and temporoparietal cortex showed differential levels of NO. Receptor autoradiography revealed increases in D1 receptor levels in the NAcc (shell), while decreases in D2 receptor binding were observed in the CPu and NAcc (core). Amphetamine and quinpirole treatments resulted in increases in locomotion. In contrast, treatment with 7-OH-DPAT produced hypolocomotion at low doses, while increased locomotion was seen at the highest dose. These results show that modulation of NO levels early postnatally (PD4-6) produces long term alteration in NO levels, with possible consequences on DA transmission, and related behaviors relevant to schizophrenia.

  1. Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuraminic acid concentration in cerebrum of young rats

    Directory of Open Access Journals (Sweden)

    Brusque A.M.

    2001-01-01

    Full Text Available Levels of methylmalonic acid (MMA comparable to those of human methylmalonic acidemia were achieved in blood (2-2.5 mmol/l and brain (1.35 µmol/g of rats by administering buffered MMA, pH 7.4, subcutaneously twice a day from the 5th to the 28th day of life. MMA doses ranged from 0.76 to 1.67 µmol/g as a function of animal age. Control rats were treated with saline in the same volumes. The animals were sacrificed by decapitation on the 28th day of age. Blood was taken and the brain was rapidly removed. Medulla, pons, the olfactory lobes and cerebellum were discarded and the rest of the brain ("cerebrum" was isolated. Body and "cerebrum" weight were measured, as well as the cholesterol and triglyceride concentrations in blood and the content of myelin, total lipids, and the concentrations of the lipid fractions (cholesterol, glycerolipids, phospholipids and ganglioside N-acetylneuraminic acid (ganglioside-NANA in the "cerebrum". Chronic MMA administration had no effect on body or "cerebrum" weight, suggesting that the metabolites per se neither affect the appetite of the rats nor cause malnutrition. In contrast, MMA caused a significant reduction of plasma triglycerides, but not of plasma cholesterol levels. A significant diminution of myelin content and of ganglioside-NANA concentration was also observed in the "cerebrum". We propose that the reduction of myelin content and ganglioside-NANA caused by MMA may be related to the delayed myelination/cerebral atrophy and neurological dysfunction found in methylmalonic acidemic children.

  2. Kinetics of removal of intravenous testosterone pulses in normal men.

    Science.gov (United States)

    Veldhuis, Johannes D; Keenan, Daniel M; Liu, Peter Y; Takahashi, Paul Y

    2010-04-01

    Testosterone is secreted into the bloodstream episodically, putatively distributing into total, bioavailable (bio) nonsex hormone-binding globulin (nonSHBG-bound), and free testosterone moieties. The kinetics of total, bio, and free testosterone pulses are unknown. Design Adrenal and gonadal steroidogenesis was blocked pharmacologically, glucocorticoid was replaced, and testosterone was infused in pulses in four distinct doses in 14 healthy men under two different paradigms (a total of 220 testosterone pulses). Testosterone kinetics were assessed by deconvolution analysis of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone concentration-time profiles. Independently of testosterone dose or paradigm, rapid-phase half-lives (min) of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone were comparable at 1.4+/-0.22 min (grand mean+/-S.E.M. of geometric means). Slow-phase testosterone half-lives were highest for SHBG-bound testosterone (32 min) and total testosterone (27 min) with the former exceeding that of free testosterone (18 min), bioavailable testosterone (14 min), and albumin-bound testosterone (18 min; Pmimicry of physiological pulses, and deconvolution analysis may have utility in estimating the in vivo kinetics of other hormones, substrates, and metabolites.

  3. the effect of orchidectomy and administration of testosterone ...

    African Journals Online (AJOL)

    20 g/day of Mouse Comproid meal (Rhomil, Ltd., Salis- bury) (Ration B) ... These differences were greater for rats fed Ration A than .... ly in excess (P < 0,00 I) of the level noted in control intact rats as regards mass of secondary sex organs. No difference in androgenic potency was detectable between the two steroids used.

  4. The effects of competition and implicit power motive on men's testosterone, emotion recognition, and aggression.

    Science.gov (United States)

    Vongas, John G; Al Hajj, Raghid

    2017-06-01

    A contribution to a special issue on Hormones and Human Competition. We investigated the effects of competition on men's testosterone levels and assessed whether androgen reactivity was associated with subsequent emotion recognition and reactive and proactive aggression. We also explored whether personalized power (p Power) moderated these relationships. In Study 1, 84 males competed on a number tracing task and interpreted emotions from facial expressions. In Study 2, 72 males competed on the same task and were assessed on proactive and reactive aggression. In both studies, contrary to the biosocial model of status (Mazur, 1985), winners' testosterone levels decreased significantly while losers' levels increased, albeit not significantly. Personalized power moderated the effect of competition outcome on testosterone change in both studies. Using the aggregate sample, we found that the effect of decreased testosterone levels among winners (compared to losers) was significant for individuals low in p Power but not for those with medium or high p Power. Testosterone change was positively related to emotion recognition, but unrelated to either aggression subtype. The testosterone-mediated relationship between winning and losing and emotion recognition was moderated by p Power. In addition, p Power moderated the direct (i.e., non-testosterone mediated) path between competition outcome and emotion recognition and both types of aggression: high p-Power winners were more accurate at deciphering others' emotions than high p-Power losers. Finally, among high p-Power men, winners aggressed more proactively than losers, whereas losers aggressed more reactively than winners. Collectively, these studies highlight the importance of implicit power motivation in modulating hormonal, cognitive, and behavioral outcomes arising from human competition. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring.

    Science.gov (United States)

    Intapad, Suttira; Dasinger, John Henry; Fahling, Joel M; Backstrom, Miles A; Alexander, Barbara T

    2017-01-01

    Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis.

  6. Relationship between Testosterone, Oxidative Stress Biomarkers ...

    African Journals Online (AJOL)

    Hypogonadism attributable to males with metabolic syndrome was also observed in automechanics occupationally exposed to mixed chemicals accompanied by oxidative stress (OS). We evaluated associations among testosterone, OS biomarkers, enzymatic and non-enzymatic antioxidants in normal weight ...

  7. Testosterone and disinhibited personality in healthy males.

    Science.gov (United States)

    Aluja, Anton; García, Luis F; García, Óscar; Blanco, Eduardo

    2016-10-01

    The relationship among testosterone (T), free testosterone (FT), bioavailable testosterone (BT) and personality were studied in a sample of 105 healthy males (26.71±9.68years old). The possible effects of age and other hormones, such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), and albumin (ALB) were controlled. Personality was assessed by the novelty seeking scale of Cloninger's Temperament-Character Inventory (TCI), and a reduced version of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Main results show that there is a weak association among three measures of testosterone with novelty seeking, sociability and, to a lesser extent, with impulsive sensation seeking. Our data, as expected, confirmed previous results and also suggest that these relationships are strongly affected by the age variable. LH, FSH and SHBG hormones play no role in the reported relationships. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. [Patient with testosterone deficit syndrome and dyslipemia].

    Science.gov (United States)

    Sola Galarza, Ignacio; López López, Borja; Llorente Abarca, Carlos

    2013-09-01

    We define dyslipemia as the abnormally elevated presence of lipids in the blood. The main ones are hypercholesterolemia (cholesterol over 240 mg/dl), hypertrigliceridemia (triglicerides level over 200 mg/dl) and hipo-alphalipoproteinemia (High density lipoproteins,also called HDL Cholesterol, below 40 mg/dl). The presence of excessive lipids contributes to arteriosclerosis and they are an independent cardiovascular risk factor. It may be primary, if they have genetic origin and they are not associated with other diseases, but in most cases they are secondary to other pathological entities such as diabetes, hypothyroidism, obesity and metabolic syndrome (MS). In our current society, sedentary lifestyle and unadequatelly hypercaloric diets are making obesity and MS prevalences grow, and their relation to dyslipemias has become tighter. Obesity is related with all the criteria for MS. But obesity is not at all synonymous of MS. On the one hand neither fat distribution is the same in all individualas nor confers the same risk. Accordingly, we know that abdominal localization of fat is related to higher intensity of insulin resistance (IR) and MS. On the other hand, it seems that certain components of MS are determined by genetic factors, since there are morbid obese persons that are metabolically healthy and other patients develop insulin resistance without obesity. So that, it seems that the excess in visceral adiposity in the presence of certain genetic factors would be the most related cause of the appearance of peripheral insulin resistance and diabetes mellitus, hyperlipidemia (increase of very low density pipoproteins (VLDL), decrease of highdensity lipoproteins (HDL) arterial hypertension, and hypogonadotropic hypogonadism, composing what we call metabolic syndrome. In this scenario, we urologists are being first-hand witnesses.On the one hand, and in relation with cardiovascular risk factors, we know that all of them, and independently,not only can produce

  9. The Association of Serum Testosterone Levels and Urinary Incontinence in Women.

    Science.gov (United States)

    Kim, Michelle M; Kreydin, Evgeniy I

    2017-08-26

    Pelvic floor integrity is an important predictor of stress urinary incontinence. Androgen receptors have been found in the pelvic floor musculature and fascia, and testosterone administration has been shown to increase levator ani hypertrophy and improve stress incontinence in a rodent model. We examined the relationship between serum total testosterone levels and self-reported urinary incontinence in women. We included women older than 20 years in the 2012 NHANES (National Health and Nutrition Examination Survey) cycle who underwent serum total testosterone measurement and answered self-reported urinary incontinence questions. A weighted, multivariate logistic regression model was used to determine the association between incontinence and serum testosterone levels after adjusting for age, body mass index, diabetes, race, parity, menopause and time of venipuncture. A total of 2,321 women were included in analysis, of whom 37.5% had stress incontinence, 29.8% had urge incontinence and 16.4% had mixed incontinence. Women in the lowest quartile of serum testosterone were more likely to complain of stress and mixed incontinence (OR 1.45, 95% CI 1.03-2.12 and OR 1.68, 95% CI 1.23-2.22, respectively). No association was noted between serum testosterone levels and urge incontinence. Low serum testosterone is associated with an increased likelihood of stress and mixed incontinence in women. Given the role of pelvic musculature in maintaining urethral support and the anabolic effect of androgens on skeletal muscle, a physiological mechanism for this relationship can be proposed and further evaluated in prospective and translational studies. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. The conjoint effect of reduced crystalloid administration and decreased damage-control laparotomy use in the development of abdominal compartment syndrome.

    Science.gov (United States)

    Joseph, Bellal; Zangbar, Bardiya; Pandit, Viraj; Vercruysse, Gary; Aziz, Hassan; Kulvatunyou, Narong; Wynne, Julie; O'Keeffe, Terence; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2014-02-01

    Anticipation of abdominal compartment syndrome (ACS) is a factor for performing damage-control laparotomy (DCL). Recent years have seen changes in resuscitation patterns and a decline in the use of DCL. We hypothesized that reductions in both crystalloid resuscitation and the use of DCL is associated with a reduced rate of ACS in trauma patients. We reviewed the records of all patients who underwent trauma laparotomies at our Level 1 trauma center over a 6-year period (2006-2011). We defined DCL as a trauma laparotomy in which the fascia was not closed at the initial operation. We defined ACS by elevated intravesical pressures and end-organ dysfunction. Our primary outcome measure was a development of ACS. A total of 799 patients were included. We noted a significant decrease in the DCL rate (39% in 2006 vs. 8% in 2011, p product volume per patient (p = 0.67). On multivariate regression analysis, crystalloid resuscitation (p = 0.01) was the only significant factor associated with the development of ACS. Minimizing the use of crystalloids and DCL was associated with better outcomes and virtual elimination of ACS in trauma patients. With the adaption of new resuscitation strategies, goals for a trauma laparotomy should be definitive surgical care with abdominal closure. ACS is a rare complication in the era of damage-control resuscitation and may have been iatrogenic. Epidemiologic/therapeutic study, level IV.

  11. Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression.

    Science.gov (United States)

    Wang, Xueting; Pan, Longlu; Zou, Zhiran; Wang, Dan; Lu, Yapeng; Dong, Zhangji; Zhu, Li

    2017-03-07

    Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis.

  12. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells.

    Science.gov (United States)

    Rato, Luís; Alves, Marco G; Duarte, Ana I; Santos, Maria S; Moreira, Paula I; Cavaco, José E; Oliveira, Pedro F

    2015-09-01

    The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Parental care, loss of paternity and circulating levels of testosterone and corticosterone in a socially monogamous song bird.

    Science.gov (United States)

    Villavicencio, Camila P; Apfelbeck, Beate; Goymann, Wolfgang

    2014-02-12

    In biparental birds testosterone levels of males are typically high during the mating phase and decrease during the parental phase. Testosterone implants may enhance mating behaviors, increase the likelihood of males to engage in extra-pair mating behavior and may reduce paternal care. Thus, sex steroids such as testosterone influence reproductive behaviors. Little is known, however, as to whether the more subtle differences in physiological concentrations of testosterone that occur between individuals are related to differences in paternal care, extra-pair behavior, and genetic paternity between those males. Here, we investigate these relationships in the male black redstart (Phoenicurus ochruros), a socially monogamous songbird with a low breeding synchrony. We used nestling provisioning as a proxy for parental care behavior and genetic paternity loss as a proxy for the efficiency of mate-guarding. There was no relationship between nestling provisioning and paternity loss of males. Baseline and gonadotropin releasing hormone (GnRH)-induced levels of testosterone, but not baseline corticosterone, were significantly higher during the mating than during the provisioning phase. Males fed more often when temperatures decreased and fed less when they sang more, but we found no correlation between parental behavior and baseline or GnRH-induced testosterone, and baseline corticosterone - both measured during either the mating or the parental phase. However, males that experienced loss of paternity had lower levels of testosterone during the provisioning phase than males that did not lose paternity. Further, males that lost paternity also expressed higher baseline levels of corticosterone. Physiological differences in testosterone or baseline corticosterone were not related to differences in parental care, suggesting that the variation of testosterone within a physiological range may not relate to the degree of paternal care in this species. However, the profile of both

  14. Physiological testosterone retards cardiomyocyte aging in Tfm mice via androgen receptor-independent pathway.

    Science.gov (United States)

    Zhang, Li; Lei, Da; Zhu, Gui-Ping; Hong, Lei; Wu, Sai-Zhu

    2013-06-01

    To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor (AR)-dependent pathway or conversion to estradiol. Male littermates and testicular feminized (Tfm) mice were randomly separated into 4 experimental groups littermate controls (n=8), Tfm mice (n=7), testosterone-treated Tfm mice (n=8), and Tfm mice treated with testosterone in combination with the aromatase inhibitor anastrazole (n=7). Cardiomyocytes were isolated from mouse left ventricles, the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the amount of malondialdehyde (MDA) were measured using colorimetry method, and expression of p16(INK4α) and retinoblastoma (Rb) proteins were detected by Western blotting. The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p16(INK4α) and Rb proteins were increased in Tfm mice compared with control mice. An increase was observed in the activities of SOD and GSH-Px enzyme as well as a decrease in MDA levels and the expression of p16(INK4α) and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhibited. Physiological testosterone replacement can delay cardiomyocyte aging in Tfm mice, an effect that is independent of the AR pathway and in part conversion to estradiol.

  15. Modulating testosterone pathway: a new strategy to tackle male skin aging?

    Science.gov (United States)

    Bernard, Philippe; Scior, Thomas; Do, Quoc Tuan

    2012-01-01

    In men, the level of testosterone decreases with age. At the skin level, the result is observed as a decrease in density and in a lower elasticity. Identifying compounds that are able to increase the level of testosterone appears to be an attractive strategy to develop new antiaging bioactive ingredients for men. Reverse pharmacognosy was successfully applied to identify new natural compounds able to modulate testosterone levels. Among several in silico hits, honokiol was retained as a candidate as it has the greatest potential to become an active ingredient. This result was then validated in vitro on aromatase and 5-alpha-reductase type 1 and 2, which are two types of enzymes implicated in the degradation of free testosterone. Indeed, honokiol was identified as an inhibitor of aromatase, with a half-maximal inhibitory concentration (IC(50)) of about 50 μM. In addition, honokiol was shown to be an inhibitor of 5-alpha-reductase type 1, with an IC(50) of about 75 μM. Taken together, these data indicate that honokiol modulates testosterone levels, and its structure has the potential to serve as a lead for future designs of highly selective inhibitors of 5-alpha-reductase type 1.

  16. [Acne fulminans following high-dose testosterone treatment in tall boys].

    Science.gov (United States)

    von Mühlendahl, K E; Brämswig, J; Traupe, H; Happle, R

    1989-05-05

    In three boys, aged 12.5, 14 and 16 years, respectively, acne of the fulminans type developed after eight to twelve months' administration of 250 mg testosterone weekly or 500 mg every second week. Numerous deep and painful pustules grew, dominantly on the chest and back, in one of the boys also in the face. In addition fever and fatiguability set in, as well as bone and joint pains in some. Erythrocyte sedimentation rate and leukocyte counts were raised. Testosterone was at once discontinued and isotretinoin, in one boy also antibiotics, administered, this treatment lasting for 8 to 13 months. All three boys were left with disfiguring scars. Before testosterone is given to arrest growth in tall boys both patient and parents should be told of these potentially severe side effects.

  17. KAJIAN TINGKAT KECENDERUNGAN PRIA DENGAN TESTOSTERON DEFICIENSI SYNDROM TERHADAP RISIKO MENDERITA METABOLIC SYNDROM

    Directory of Open Access Journals (Sweden)

    Bambang Wasito

    2012-11-01

    Full Text Available Man above 50 years old, as women who experience menopause, will show certain and specific problems. Middle age man often has a group of complaints, symptoms and syndromes that almost the same as women. The total populationof old citizen in the whole world keeps on increasing from year to year; so in Indonesia. There was prediction that the increment of total of old population in Indonesia will increase into 41% in 2020 (WHO report. With the addition of age, there is a decrease of testosterone production and it will be followed with the decrease of production of other hormones, enzymes, bio active that needed by body to be able to survive in performing active and healthy life. Massachusetts Male Aging Study (MMAS, 1991 and Vermeulen (1992 report that start from 40 years old, a man will experience the decrease of active blood testosterone level around 1.2% per year and it happens until the age 70 years old, in which the man will experience blood testosterone level decrease into 35% from previous normal level. Testosterone Deficiency Syndrome (TDS or Hypogonadism can be diagnosed well by measuring active testosterone level in laboratory Metabolic syndrome is a group of metabolic disorder, in which lipid or non lipid can be the factor of coronary disease, that consists of centralobesity, displipedimia alerogenic (high trigliserid level and low level of HDL cholesterol, hypertension, and abnormal glucoseplasma, and it often experienced by man above 40 years old. A man with erection dysfunction is initial manifestation of vascular disease. Risk factor for cardiovascular disease such as hypertension, dislipidemia, central obesity and insulin resistance is also the same risk factor for erection dysfunction that caused by vascular. Risk factor of erection dysfunction will increase for metabolic syndrome. Key words: Aging man, metabolic syndrome, Testosterone Deficiency Syndrome

  18. Testosterone increases renal anti-aging klotho gene expression via the androgen receptor-mediated pathway.

    Science.gov (United States)

    Hsu, Shih-Che; Huang, Shih-Ming; Lin, Shih-Hua; Ka, Shuk-Man; Chen, Ann; Shih, Meng-Fu; Hsu, Yu-Juei

    2014-12-01

    Gender is known to be associated with longevity and oestrogen administration induced longevity-associated gene expression is one of the potential mechanisms underlying the benefits of oestrogen on lifespan, whereas the role of testosterone in the regulation of longevity-associated gene expressions remains largely unclear. The klotho gene, predominantly expressed in the kidney, has recently been discovered to be an aging suppressor gene. In the present study, we investigated the regulatory effects of testosterone on renal klotho gene expression in vivo and in vitro. In testosterone-administered mouse kidney and NRK-52E cells, increased klotho expression was accompanied by the up-regulation of the nuclear androgen receptor (AR). Overexpression of AR enhanced the expression of klotho mRNA and protein. Conversely, testosterone-induced klotho expression was attenuated in the presence of flutamide, an AR antagonist. A reporter assay and a chromatin immunoprecipitation (ChIP) assay demonstrated that AR directly binds to the klotho promoter via androgen response elements (AREs) which reconfirmed its importance for AR binding via the element mutation. In summary, our study demonstrates that testosterone up-regulates anti-aging klotho together with AR expression in the kidney in vivo and in vitro by recruiting AR on to the AREs of the klotho promoter.

  19. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    Science.gov (United States)

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats. Copyright © 2015. Published by Elsevier Ltd.

  20. BINGE ALCOHOL ADMINISTRATION ON PREGNANT RATS RESULTS IN DECREASING OF INSULIN LIKE GROWTH FACTOR-1 AND ALDEHYDE DEHYDROGENASE, INCREASING APOPTOSIS INDEX, AND FETAL ALCOHOL SYNDROME IN OFFSPRINGS

    Directory of Open Access Journals (Sweden)

    S. Suherman

    2016-01-01

    Full Text Available Background: Addiction of alcoholic beverage by early pregnancy women results in fetal alcohol syndrome of her baby. This study aims to investigate fetal alcoholic syndrome due to binge alcoholic drinking by the early pregnant of wistar rat. Methods: This is an experimental study applying posttest only control group design. Wistar Rats were in preconditioning for pregnancy and divided into two groups, i.e. one group was fed with normal feeding and the other group was fed with normal feeding and 40% of ethanol. The off spring then were observed and divided into three groups, i.e. normal fetal, normal fetal from the mother fed with ethanol, and fetal alcoholic syndrome. Insulin like growth factor (IGF-1, aldehyde dehydrogenase (ALDH, apoptosis index, pathology of their brain and heart were observed. The different of all these parameters were then compared by applying one way anova, and considered significant at p < 0.05. Results: In this study we found that there were fetals alcoholic syndrome (FAS due to the mother of the Wistar Rat fed with ethanol during their pregnancy. There were also a significant different of IGF-1, ALDH, apoptosis index between these three groups (p < 0.05, i.e. normal baby, normal fed with ethanol, and FAS. IGF-1 for these three groups were 56.59±0.52 ng/ml, 55.17±2.41 ng/ml, and 36.64±4.86 ng/ml, respectively. ALDH for the groups were 21.41±2.38 ng/ml, 21.16±4.77 ng/ml, and 17.05±2.68 ng/ml, respectively. Their brain apoptosis indexes were 4.56±0.78, 4.58±1.17, and 7.86±1.31, respectively. Heart apoptosis indexes were found 2.81±1.18, 5.36±1.37, and 7.50±1.43, respectively. Conclusion: Binge alcohol drinking during pregnancy of Wistar Rat results in FAS and identified by decrease of IGF-1, ALDH and increase of brain apoptosis index and heart apoptosis index of the off spring.

  1. Quality improvements in decreasing medication administration errors made by nursing staff in an academic medical center hospital: a trend analysis during the journey to Joint Commission International accreditation and in the post-accreditation era

    Directory of Open Access Journals (Sweden)

    Wang HF

    2015-03-01

    Full Text Available Hua-fen Wang,1 Jing-fen Jin,1 Xiu-qin Feng,1 Xin Huang,1 Ling-ling Zhu,2 Xiao-ying Zhao,3 Quan Zhou4 1Division of Nursing, 2Geriatric VIP Ward, Division of Nursing, 3Office of Quality Administration, 4Department of Pharmacy, the Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Medication errors may occur during prescribing, transcribing, prescription auditing, preparing, dispensing, administration, and monitoring. Medication administration errors (MAEs are those that actually reach patients and remain a threat to patient safety. The Joint Commission International (JCI advocates medication error prevention, but experience in reducing MAEs during the period of before and after JCI accreditation has not been reported. Methods: An intervention study, aimed at reducing MAEs in hospitalized patients, was performed in the Second Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of China, during the journey to JCI accreditation and in the post-JCI accreditation era (first half-year of 2011 to first half-year of 2014. Comprehensive interventions included organizational, information technology, educational, and process optimization-based measures. Data mining was performed on MAEs derived from a compulsory electronic reporting system. Results: The number of MAEs continuously decreased from 143 (first half-year of 2012 to 64 (first half-year of 2014, with a decrease in occurrence rate by 60.9% (0.338% versus 0.132%, P<0.05. The number of MAEs related to high-alert medications decreased from 32 (the second half-year of 2011 to 16 (the first half-year of 2014, with a decrease in occurrence rate by 57.9% (0.0787% versus 0.0331%, P<0.05. Omission was the top type of MAE during the first half-year of 2011 to the first half-year of 2014, with a decrease by 50% (40 cases versus 20 cases. Intravenous administration error was the

  2. Relationship of testosterone and nonverbal intelligence to hand preference and hand skill in right-handed young adults.

    Science.gov (United States)

    Tan, U

    1990-10-01

    The relationship between serum testosterone level and nonverbal intelligence was studied in right-handed young adults with regard to handedness. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was measured by a peg moving task. Serum testosterone level was determined using tritium-marked-radioimmunoassay. Visual-spatial performance (nonverbal intelligence) was measured by Cattell's Culture Fair Intelligence Test. In men with consistent right-hand preference (GSs: 80 to 100), IQ was found to be positively linearly related to serum testosterone, which exhibited two regression lines belonging to low and high difference in skill between hands. In females with consistent right-handedness, there was a negative linear correlation between IQ and serum testosterone, which also exhibited two different regression lines according to difference in skill between hands. In males with moderate right-hand preference (GSs 50 to 75), IQ was found to be positively linearly related to serum testosterone, exhibiting two different (same slopes) regression lines according to difference in skill between hands. In females with moderate right-hand preference, IQ first increased and then decreased with serum testosterone, exhibiting a quadratic relationship. These results suggested that serum testosterone in young adults may be associated with visual-spatial performance depending upon sex, hand preference, and hand skill.

  3. Total testosterone in young men is more closely associated than free testosterone with prostate cancer disparities

    OpenAIRE

    Alvarado, Louis Calistro

    2011-01-01

    Introduction: Early adulthood has been suggested as the most relevant time to determine the influence of testosterone on prostate carcinogenesis. For a more detailed assessment of this hypothesis, the present study examined whether serum total or free testosterone in young men was more closely associated with prostate cancer disparities.

  4. Quality improvements in decreasing medication administration errors made by nursing staff in an academic medical center hospital: a trend analysis during the journey to Joint Commission International accreditation and in the post-accreditation era.

    Science.gov (United States)

    Wang, Hua-Fen; Jin, Jing-Fen; Feng, Xiu-Qin; Huang, Xin; Zhu, Ling-Ling; Zhao, Xiao-Ying; Zhou, Quan

    2015-01-01

    Medication errors may occur during prescribing, transcribing, prescription auditing, preparing, dispensing, administration, and monitoring. Medication administration errors (MAEs) are those that actually reach patients and remain a threat to patient safety. The Joint Commission International (JCI) advocates medication error prevention, but experience in reducing MAEs during the period of before and after JCI accreditation has not been reported. An intervention study, aimed at reducing MAEs in hospitalized patients, was performed in the Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China, during the journey to JCI accreditation and in the post-JCI accreditation era (first half-year of 2011 to first half-year of 2014). Comprehensive interventions included organizational, information technology, educational, and process optimization-based measures. Data mining was performed on MAEs derived from a compulsory electronic reporting system. The number of MAEs continuously decreased from 143 (first half-year of 2012) to 64 (first half-year of 2014), with a decrease in occurrence rate by 60.9% (0.338% versus 0.132%, Pmedications decreased from 32 (the second half-year of 2011) to 16 (the first half-year of 2014), with a decrease in occurrence rate by 57.9% (0.0787% versus 0.0331%, Pmedication errors. The number of MAEs in surgical wards was twice that in medicinal wards. Compared with non-intensive care units, the intensive care units exhibited higher occurrence rates of MAEs (1.81% versus 0.24%, Pmedication administration. JCI accreditation may help health systems enhance the awareness and ability to prevent MAEs and achieve successful quality improvements.

  5. Fourteen days oral administration of therapeutic dosage of some ...

    African Journals Online (AJOL)

    Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

  6. Adult testosterone and calculated free testosterone reference ranges by tandem mass spectrometry.

    Science.gov (United States)

    Neale, S M; Hocking, R; Biswas, M; Turkes, A; Rees, D; Rees, D A; Evans, C

    2013-03-01

    Testosterone is measured for the investigation of female hyperandrogenism and male hypogonadism. Liquid chromatography-tandem mass spectrometry (tandem MS) is becoming the method of choice but comprehensive reference ranges are lacking. Testosterone was measured by tandem MS on 90 healthy women, 67 young healthy men and pregnant women (59 first trimester and 60 second trimester). The male, male calculated free, first trimester and second trimester testosterone reference ranges (derived using the antilog of mean ± 1.96 SD of log transformed data) were 10.6-31.9, 0.23-0.63, 0.6-4.9 and 0.9-4.9 nmol/L, respectively. The female testosterone upper reference range limit, derived non-parametrically from the 97.5th centile, was testosterone reference ranges to support clinical services.

  7. Low testosterone level increases fasting blood glucose level in adult males

    Directory of Open Access Journals (Sweden)

    Suweino

    2012-12-01

    Full Text Available Background Total testosterone (TT levels in males decrease with age. There has been a vigorous debate on the extent to which low testosterone causally contributes to diabetes and its complications. The aim of the present study was to determine the relationship between sex hormones and blood glucose levels in adult males. Methods A cross-sectional study involving 259 males aged 41 - 70 years was conducted at Cilandak Subdistrict, South Jakarta. Sex hormone binding globulin (SHBG and testosterone levels were measured by means of electro–chemiluminescent immunoassay (ECLIA, while blood glucose levels were measured enzymatically using a spectrophotometer. Free testosterone index (FTI and body massa index (BMI were calculated. Inter-variable relationships were tested by Pearson correlation analysis, followed by multiple linear regression analysis to determine the most influential factor on fasting blood glucose levels. Results BMI was positively correlated with fasting blood glucose, but the correlation was statistically not significant (r=0.105; p=0.106. In contrast, total testosterone (TT (r=-0.258; p=0.000 and SHBG (r=-0.193; p=0.02 had a significant negative correlation with fasting blood glucose level. Multiple linear regression showed that TT was the most influential factor on fasting blood glucose level (â=-0.044; p=0.008. Conclusions Low total testosterone level may increase fasting blood glucose level in adult males. SHBG levels did not predict fasting blood glucose levels.Assessment of testosterone in middle-aged men may allow early intervention for diabetes mellitus.

  8. Low testosterone level increases fasting blood glucose level in adult males

    Directory of Open Access Journals (Sweden)

    Suweino Suweino

    2015-12-01

    Full Text Available BACKGROUND Total testosterone (TT levels in males decrease with age. There has been a vigorous debate on the extent to which low testosterone causally contributes to diabetes and its complications. The aim of the present study was to determine the relationship between sex hormones and blood glucose levels in adult males. METHODS A cross-sectional study involving 259 males aged 41 - 70 years was conducted at Cilandak Subdistrict, South Jakarta. Sex hormone binding globulin (SHBG and testosterone levels were measured by means of electro–chemiluminescent immunoassay (ECLIA, while blood glucose levels were measured enzymatically using a spectrophotometer. Free testosterone index (FTI and body massa index (BMI were calculated. Inter-variable relationships were tested by Pearson correlation analysis, followed by multiple linear regression analysis to determine the most influential factor on fasting blood glucose levels. RESULTS BMI was positively correlated with fasting blood glucose, but the correlation was statistically not significant (r=0.105; p=0.106. In contrast, total testosterone (TT (r=-0.258; p=0.000 and SHBG (r=-0.193; p=0.02 had a significant negative correlation with fasting blood glucose level. Multiple linear regression showed that TT was the most influential factor on fasting blood glucose level (â=-0.044; p=0.008. CONCLUSIONS Low total testosterone level may increase fasting blood glucose level in adult males. SHBG levels did not predict fasting blood glucose levels.Assessment of testosterone in middle-aged men may allow early intervention for diabetes mellitus.

  9. A novel testosterone catabolic pathway in bacteria.

    Science.gov (United States)

    Leu, Yann-Lii; Wang, Po-Hsiang; Shiao, Ming-Shi; Ismail, Wael; Chiang, Yin-Ru

    2011-09-01

    Forty years ago, Coulter and Talalay (A. W. Coulter and P. Talalay, J. Biol. Chem. 243:3238-3247, 1968) established the oxygenase-dependent pathway for the degradation of testosterone by aerobes. The oxic testosterone catabolic pathway involves several oxygen-dependent reactions and is not available for anaerobes. Since then, a variety of anaerobic bacteria have been described for the ability to degrade testosterone in the absence of oxygen. Here, a novel, oxygenase-independent testosterone catabolic pathway in such organisms is described. Steroidobacter denitrificans DSMZ18526 was shown to be capable of degrading testosterone in the absence of oxygen and was selected as the model organism in this study. In a previous investigation, we identified the initial intermediates involved in an anoxic testosterone catabolic pathway, most of which are identical to those of the oxic pathway demonstrated in Comamonas testosteroni. In this study, five additional intermediates of the anoxic pathway were identified. We demonstrated that subsequent steps of the anoxic pathway greatly differ from those of the established oxic pathway, which suggests that a novel pathway for testosterone catabolism is present. In the proposed anoxic pathway, a reduction reaction occurs at C-4 and C-5 of androsta-1,4-diene-3,17-dione, the last common intermediate of both the oxic and anoxic pathways. After that, a novel hydration reaction occurs and a hydroxyl group is thus introduced to the C-1α position of C(19)steroid substrates. To our knowledge, an enzymatic hydration reaction occurring at the A ring of steroid compounds has not been reported before.

  10. Transcriptomic analysis of hepatic responses to testosterone deficiency in miniature pigs fed a high-cholesterol diet.

    Science.gov (United States)

    Cai, Zhaowei; Jiang, Xiaoling; Pan, Yongming; Chen, Liang; Zhang, Lifan; Zhu, Keyan; Cai, Yueqin; Ling, Yun; Chen, Fangming; Xu, Xiaoping; Chen, Minli

    2015-02-06

    Recent studies have indicated that low serum testosterone levels are associated with increased risk of developing hepatic steatosis; however, the mechanisms mediating this phenomenon have not been fully elucidated. To gain insight into the role of testosterone in modulating hepatic steatosis, we investigated the effects of testosterone on the development of hepatic steatosis in pigs fed a high-fat and high-cholesterol (HFC) diet and profiled hepatic gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT). Serum testosterone levels were significantly decreased in CM pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. CM pigs showed increased liver injury accompanied by increased hepatocellular steatosis, inflammation, and elevated serum alanine aminotransferase levels compared with IM pigs. Moreover, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were markedly increased in CM pigs. Testosterone replacement decreased serum and hepatic lipid levels and improved liver injury in CM pigs. Compared to IM and CMT pigs, CM pigs had lower serum levels of superoxide dismutase but higher levels of malondialdehyde. Gene expression analysis revealed that upregulated genes in the livers of CM pigs were mainly enriched for genes mediating immune and inflammatory responses, oxidative stress, and apoptosis. Surprisingly, the downregulated genes mainly included those that regulate metabolism-related processes, including fatty acid oxidation, steroid biosynthesis, cholesterol and bile acid metabolism, and glucose metabolism. KEGG analysis showed that metabolic pathways, fatty acid degradation, pyruvate metabolism, the tricarboxylic acid cycle, and the nuclear factor-kappaB signaling pathway were the major pathways altered in CM pigs. This study demonstrated that testosterone deficiency aggravated

  11. Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

    Science.gov (United States)

    Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

    2016-11-01

    Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled

  12. Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial.

    Science.gov (United States)

    Gianatti, Emily J; Dupuis, Philippe; Hoermann, Rudolf; Strauss, Boyd J; Wentworth, John M; Zajac, Jeffrey D; Grossmann, Mathis

    2014-08-01

    To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35-70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo -0.08 [95% CI -0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0-0.7]; P = 0.05), despite a decrease in fat mass (MAD -2.38 kg [-3.10 to -1.66]; P Testosterone therapy reduced subcutaneous (MAD -320 cm(3) [-477 to -163]; P Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Negative regulation of glucose metabolism in human myotubes by supraphysiological doses of 17β-estradiol or testosterone.

    Science.gov (United States)

    Garrido, Pablo; Salehzadeh, Firoozeh; Duque-Guimaraes, Daniella E; Al-Khalili, Lubna

    2014-09-01

    Exposure of skeletal muscle to high levels of testosterone or estrogen induces insulin resistance, but evidence regarding the direct role of either sex hormone on metabolism is limited. Therefore, the aim of this study was to investigate the direct effect of acute sex hormone exposure on glucose metabolism in skeletal muscle. Differentiated human skeletal myotubes were exposed to either 17β-estradiol or testosterone and metabolic characteristics were assessed. Glucose incorporation into glycogen, glucose oxidation, palmitate oxidation, and phosphorylation of key signaling proteins were determined. Treatment of myotubes with either 17β-estradiol or testosterone decreased glucose incorporation into glycogen. Exposure of myotubes to 17β-estradiol reduced glucose oxidation under basal and insulin-stimulated conditions. However, testosterone treatment enhanced basal palmitate oxidation and prevented insulin action on glucose and palmitate oxidation. Acute stimulation of myotubes with testosterone reduced phosphorylation of S6K1 and p38 MAPK. Exposure of myotubes to either 17β-estradiol or testosterone augmented phosphorylation GSK3β(Ser9) and PKCδ(Thr505), two negative regulators of glycogen synthesis. Treatment of myotubes with a PKC specific inhibitor (GFX) restored the effect of either sex hormone on glycogen synthesis. PKCδ silencing restored glucose incorporation into glycogen to baseline in response to 17β-estradiol, but not testosterone treatment. An acute exposure to supraphysiological doses of either 17β-estradiol or testosterone regulates glucose metabolism, possibly via PKC signaling pathways. Furthermore, testosterone treatment elicits additional alterations in serine/threonine kinase signaling, including the ribosomal protein S6K1 and p38 MAPK. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Genetic Determinants of Serum Testosterone Concentrations in Men

    Science.gov (United States)

    Maggio, Marcello; Coviello, Andrea D.; Ferrucci, Luigi; Heier, Margit; Hofman, Albert; Holliday, Kate L.; Jansson, John-Olov; Kähönen, Mika; Karasik, David; Karlsson, Magnus K.; Kiel, Douglas P.; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Mattias; Lyytikäinen, Leo-Pekka; Meitinger, Thomas; Mellström, Dan; Melzer, David; Miljkovic, Iva; Nauck, Matthias; Nilsson, Maria; Penninx, Brenda; Pye, Stephen R.; Vasan, Ramachandran S.; Reincke, Martin; Rivadeneira, Fernando; Tajar, Abdelouahid; Teumer, Alexander; Uitterlinden, André G.; Ulloor, Jagadish; Viikari, Jorma; Völker, Uwe; Völzke, Henry; Wichmann, H. Erich; Wu, Tsung-Sheng; Zhuang, Wei Vivian; Ziv, Elad; Wu, Frederick C. W.; Raitakari, Olli; Eriksson, Anna; Bidlingmaier, Martin; Harris, Tamara B.; Murray, Anna; de Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender; Vandenput, Liesbeth; Haring, Robin

    2011-01-01

    Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (ptestosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. PMID:21998597

  15. Prenatal Testosterone and Preschool Disruptive Behavior Disorders.

    Science.gov (United States)

    Roberts, Bethan A; Martel, Michelle M

    2013-11-01

    Disruptive Behaviors Disorders (DBD), including Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD), are fairly common and highly impairing childhood behavior disorders that can be diagnosed as early as preschool. Prenatal exposure to testosterone may be particularly relevant to these early-emerging DBDs that exhibit a sex-biased prevalence rate favoring males. The current study examined associations between preschool DBD symptom domains and prenatal exposure to testosterone measured indirectly via right 2D:4D finger-length ratios. The study sample consisted of 109 preschool-age children between ages 3 and 6 (64% males;72% with DBD) and their primary caregivers. Primary caregivers completed a semi-structured interview (i.e., Kiddie Disruptive Behavior Disorder Schedule), as well as symptom questionnaires (i.e., Disruptive Behavior Rating Scale, Peer Conflict Scale); teachers and/or daycare providers completed symptom questionnaires and children provided measures of prenatal testosterone exposure, measured indirectly via finger-length ratios (i.e., right 2D:4D). Study results indicated a significant association of high prenatal testosterone (i.e., smaller right 2D:4D) with high hyperactive-impulsive ADHD symptoms in girls but not boys, suggesting that the effect may be driven by, or might only exist in, girls. The present study suggests that prenatal exposure to testosterone may increase risk for early ADHD, particularly hyperactivity-impulsivity, in preschool girls.

  16. Measurement of cortisol and testosterone in hair of obese and non-obese human subjects.

    Science.gov (United States)

    Chan, J; Sauvé, B; Tokmakejian, S; Koren, G; Van Uum, S

    2014-06-01

    Hair analysis has been demonstrated to accurately reflect exposure to drug abuse, environmental toxins and exogenous hormones. We tested the feasibility of measuring cortisol and testosterone in hair of healthy and obese subjects. A modified immunoassay (ELISA) originally developed for saliva was used. Hair, urine and blood samples were collected from young non-obese and obese patients. Perceived stress (PSS) was measured using a validated questionnaire. There was no difference in PSS between non-obese and obese subjects. Hair cortisol levels were significantly correlated with weight (r = 0.27, p significance (p = 0.063). Hair cortisol levels did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age (r = -0.47, p significance (p = 0.098). The ratio of hair cortisol over hair testosterone (C/T) was higher in the obese group than in the young non-obese group. The C/T ratio correlated positively with age (r = 0.56, p significance. Hair cortisol levels increase, while hair testosterone levels decrease with obesity. The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone. As hair collection is non-invasive and is not influenced by moment-to-moment variations, the measurement of hormones in hair is a useful tool in research and possibly clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Earlier Debridement and Antibiotic Administration Decrease Infection

    Science.gov (United States)

    2010-01-01

    Discussion Gustilo and Anderson stated “[t]here is universal agree- ment that open fractures require emergency treatment including adequate debridement...polymethylmethacrylate beads and hip spacers in vivo. Acta Orthop. 80(2):193– 197, 2009. 10. Gustilo , R. B., Anderson, J. T. Prevention of infection

  18. Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, J H

    1987-01-01

    Liver haemodynamics and liver function were measured in 34 alcoholic cirrhotic men before entry and after 12 months (median) in a double-blind, placebo-controlled study on the effect of oral testosterone treatment (200 mg t.i.d.). Comparing data at entry with those at follow-up in the total patient......, testosterone-treated patients did not differ significantly from placebo-treated patients regarding any of the measured variables. No significant relationships could be demonstrated between ethanol consumption and liver haemodynamics and liver function, but the number of patients consuming more than 100 g...... ethanol per day decreased significantly (P less than 0.001) from 22 (65%) before entry to one (3%) during follow-up. In conclusion, oral testosterone treatment of men with alcoholic cirrhosis does not explain the significant improvement of liver haemodynamics and function observed in this study. However...

  19. Reduction of spermatogonia and testosterone in rat testes flown on Space Lab-3

    Science.gov (United States)

    Philpott, Delbert E.; Stevenson, J.; Black, S.; Sapp, W.; Williams, C.

    1986-01-01

    The effects of space flight on rat testes were investigated. The weight, spermatogonial cell count, and testosterone levels in six rats flown on Space Lab-3 were measured. It is observed that compared to ground control rats the average weight loss was 7.1 percent and the spermatogonial cell count decreased by 7.5 percent. The data reveal that the testosterone level for large control rats was 9.13 ng/ml and 0.31 ng/ml for flight rats; and 2.54 ng/ml and 0.233 ng/ml for smaller control and flight rats, respectively. It is noted that spermatogenesis and testosterone production are reduced during spaceflight.

  20. Testosterone regulates keratin 33B expression in rat penis growth through androgen receptor signaling.

    Science.gov (United States)

    Ma, Yan-Min; Wu, Kai-Jie; Dang, Qiang; Shi, Qi; Gao, Yang; Guo, Peng; Xu, Shan; Wang, Xin-Yang; He, Da-Lin; Gong, Yong-Guang

    2014-01-01

    Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR) protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b). Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.

  1. Effects of dutasteride on serum free-testosterone and clinical significance of testosterone changes.

    Science.gov (United States)

    Enatsu, N; Miyake, H; Haraguchi, T; Chiba, K; Fujisawa, M

    2016-12-01

    Sixty-two patients with benign prostate hyperplasia (BPH) who were being treated with dutasteride participated in this study. Prostate volume, uroflowmetry, blood tests, the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) were determined before and 1, 3 and 12 months after the treatment with dutasteride. Patients were divided into two groups based on changes in serum testosterone after 1 month: Group A (>20% increase; n = 33) or Group B (free-testosterone levels were 20.4% higher after 1 month and remained constant thereafter. When Groups A and B were compared, baseline free-testosterone levels were significantly lower in Group A, IPSS QOL was significantly better in Group A at 3 and 12 months, and no significant differences were observed in uroflowmetry, prostate volume, IPSS or IIEF-5. A univariate analysis identified serum free-testosterone levels and the IPSS storage symptom subscore as significant factors influencing IPSS QOL at 12 months, and only the IPSS storage symptom subscore appeared to be independently related to IPSS QOL. These results indicate that dutasteride increases serum free-testosterone levels in BPH patients, particularly with low baseline free-testosterone levels, and the increase in free-testosterone may have further add-on impacts on their urinary tract symptoms. © 2016 Blackwell Verlag GmbH.

  2. Fathers' decline in testosterone and synchrony with partner testosterone during pregnancy predicts greater postpartum relationship investment.

    Science.gov (United States)

    Saxbe, Darby E; Edelstein, Robin S; Lyden, Hannah M; Wardecker, Britney M; Chopik, William J; Moors, Amy C

    2017-04-01

    The transition to parenthood has been associated with declines in testosterone among partnered fathers, which may reflect males' motivation to invest in the family. Moreover, preliminary evidence has found that couples show correlations in hormone levels across pregnancy that may also be linked to fathers' preparation for parenthood. The current study used repeated-measures sampling of testosterone across pregnancy to explore whether fathers' change in T, and correlations with mothers' T, were associated with fathers' and mothers' postpartum investment. In a sample of 27 couples (54 individuals) expecting their first child, both parents' salivary testosterone was measured multiple times across pregnancy. At approximately 3.5months postpartum, participants rated their investment, commitment, and satisfaction with their partner. A multilevel model was used to measure change in testosterone over time and associations between mother and father testosterone. Fathers who showed stronger declines in T across pregnancy, and stronger correlations with mothers' testosterone, reported higher postpartum investment, commitment, and satisfaction. Mothers reported more postpartum investment and satisfaction if fathers showed greater prenatal declines in T. These results held even after controlling for paternal investment, commitment, and satisfaction measured prenatally at study entry. Our results suggest that changes in paternal testosterone across pregnancy, and hormonal linkage with the pregnant partner, may underlie fathers' dedication to the partner relationship across the transition to parenthood. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Wirkung von Testosteron auf Haut und Haare

    Directory of Open Access Journals (Sweden)

    Kopera D

    2015-01-01

    Full Text Available Testosteron – das wichtigste Androgen – wird ab der Adrenarche bei beiden Geschlechtern in mehr oder weniger großen Mengen gebildet. Die Bildung erfolgt bei Männern in den Hoden, bei Frauen in den Ovarien und bei beiden Geschlechtern in geringen Mengen in den Nebennieren. Im Blut zirkuliert es einerseits SHBG-gebunden, andererseits als wirksames und freies Testosteron, das auf die verschiedenen Organe eine unterschiedlich starke Wirkung ausübt. Es beeinflusst die Ausbildung des männlichen Phänotyps, den Aufbau der Muskelmasse, die Knochendichte sowie den Fett- und Zuckerstoffwechsel. Auf Haut und Hautanhangsgebilde hat Testosteron eine besondere Wirkung: Es stimuliert die Talgdrüsen (führt zu Seborrhö und reguliert das Haarwachstum.

  4. Wirkung von Testosteron auf Haut und Haare

    Directory of Open Access Journals (Sweden)

    Kopera D

    2016-01-01

    Full Text Available Testosteron – das wichtigste Androgen – wird ab der Adrenarche bei beiden Geschlechtern in mehr oder weniger großen Mengen gebildet. Die Bildung erfolgt bei Männern in den Hoden, bei Frauen in den Ovarien und bei beiden Geschlechtern in geringen Mengen in den Nebennieren. Im Blut zirkuliert es einerseits SHBG-gebunden, andererseits als wirksames und freies Testosteron, das auf die verschiedenen Organe eine unterschiedlich starke Wirkung ausübt. Es beeinflusst die Ausbildung des männlichen Phänotyps, den Aufbau der Muskelmasse, die Knochendichte sowie den Fett- und Zuckerstoffwechsel. Auf Haut und Hautanhangsgebilde hat Testosteron eine besondere Wirkung: Es stimuliert die Talgdrüsen (führt zu Seborrhö und reguliert das Haarwachstum.

  5. A Novel Testosterone Catabolic Pathway in Bacteria ▿ ‡

    OpenAIRE

    Leu, Yann-Lii; Wang, Po-Hsiang; Shiao, Ming-Shi; Ismail, Wael; Chiang, Yin-Ru

    2011-01-01

    Forty years ago, Coulter and Talalay (A. W. Coulter and P. Talalay, J. Biol. Chem. 243:3238–3247, 1968) established the oxygenase-dependent pathway for the degradation of testosterone by aerobes. The oxic testosterone catabolic pathway involves several oxygen-dependent reactions and is not available for anaerobes. Since then, a variety of anaerobic bacteria have been described for the ability to degrade testosterone in the absence of oxygen. Here, a novel, oxygenase-independent testosterone c...

  6. A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Jørgensen, Niels; Juul, Anders

    2017-01-01

    with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. Methods/design: This is a single-center, randomized, double-blind, placebo......Background: Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated......-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed...

  7. Association between low serum free testosterone and adverse ...

    African Journals Online (AJOL)

    Background. The association of serum free testosterone (FT) with prostate cancer is not fully understood. Studies on the results of the relationship between serum testosterone level and prostate cancer are conflicting. However, there is a reported association between lower serum testosterone levels and high-grade prostate ...

  8. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol benzoate...

  9. Modulation of serum concentrations and hepatic metabolism of 17{beta}-estradiol and testosterone by amitraz in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Chen-Ping [National Taiwan University, Institute of Toxicology, College of Medicine, Taipei (China); Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung (China); Lu, Shui-Yuan [Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung (China); Ueng, Tzuu-Huei [National Taiwan University, Institute of Toxicology, College of Medicine, Taipei (China)

    2008-10-15

    The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17{beta}-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomized (OVX) and 0.5 mg/kg E2-supplemented female rats for 7 days. E2 and metabolites were analyzed by gas chromatography-electron capture detection and testosterone and metabolites were analyzed by high-pressure liquid chromatography. In OVX and E2-supplemented females, 50 mg/kg amitraz caused an 85% decrease of serum E2 concentration and a marked increase of 2-OH-E2 concentration. Amitraz at 25 and 50 mg/kg produced 9.0-fold or greater increases of serum testosterone and 2{beta}-OH-testosterone levels in males. Amitraz at 25 mg/kg resulted in no or minimal increases of liver microsomal formation of E2 or testosterone metabolites. Amitraz at 50 mg/kg produced 1.4- to 3.6-fold increases of 2-OH-E2; estrone; 2{beta}-, 6{beta}-, and 16{alpha}-OH-testosterone; and androstenedione formation in males and intact females. Amitraz at 50 mg/kg preferentially increased intact female 16{beta}-OH-testosterone production by 8.6-fold. In OVX females, E2 supplement alone or cotreatment with E2 and 50 mg/kg amitraz produced 1.3- to several-fold increases of 2- and 4-OH-E2 formation and 2{beta}- and 16{alpha}-OH-testosterone production. The cotreatment increased 6{beta}- and 16{beta}-OH-testosterone formation by 1.8- and 1.6-fold, respectively. The present findings show that amitraz induces hepatic E2 and testosterone metabolism in male and female rats, decreases serum E2 concentration in OVX and E2-supplemented females, but increases serum testosterone in males. (orig.)

  10. Progressive Improvement of T-Scores in Men with Osteoporosis and Subnormal Serum Testosterone Levels upon Treatment with Testosterone over Six Years

    NARCIS (Netherlands)

    Haider, A.; Meergans, U.; Traish, A.; Saad, F.; Doros, G.; Lips, P.T.A.M.; Gooren, L.

    2014-01-01

    Testosterone deficiency leads to bone loss and testosterone treatment has a beneficial effect. This study investigated the effects of normalizing serum testosterone on bone mineral density in 45 men with osteoporosis, diagnosed with testosterone deficiency (serum testosterone levels <12.1 nmol/L,

  11. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women.

    Science.gov (United States)

    Wang, Xuewen; Smith, Gordon I; Patterson, Bruce W; Reeds, Dominic N; Kampelman, Janine; Magkos, Faidon; Mittendorfer, Bettina

    2012-03-15

    Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (∼10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P > 0.05); the muscle protein fractional synthesis rate, however, increased by ∼45% (P testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women.

  12. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone

    Energy Technology Data Exchange (ETDEWEB)

    Carney, J.M.; Starke-Reed, P.E.; Oliver, C.N.; Landum, R.W.; Cheng, M.S.; Wu, J.F.; Floyd, R.A. (Univ. of Kentucky, Lexington (USA))

    1991-05-01

    Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls.

  13. Baseline blood trihalomethanes, semen parameters and serum total testosterone: a cross-sectional study in China.

    Science.gov (United States)

    Zeng, Qiang; Li, Min; Xie, Shao-Hua; Gu, Long-Jie; Yue, Jing; Cao, Wen-Cheng; Zheng, Dan; Liu, Ai-Lin; Li, Yu-Feng; Lu, Wen-Qing

    2013-04-01

    Toxicological studies showed that trihalomethanes (THMs), the most abundant classes of disinfection by-products (DBPs) in drinking water, impaired male reproductive health, but epidemiological evidence is limited and inconsistent. This study aimed to examine the associations of baseline blood THMs with semen parameters and serum total testosterone in a Chinese population. We recruited 401 men seeking semen examination from the Reproductive Center of Tongji Hospital in Wuhan, China between April 2011 and May 2012. Baseline blood concentrations of THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were measured using SPME-GC/ECD method. Semen quality and serum total testosterone were analyzed. Multivariable linear regressions were used to assess the associations of baseline blood THM concentrations with semen parameters and serum total testosterone levels. We found that baseline blood THM concentrations were not associated with decrements in sperm motility, sperm straight-line and curvilinear velocity. However, moderate levels of BDCM (β=-0.13 million; 95% CI: -0.22, -0.03) and DBCM (β=-4.74%; 95% CI: -8.07, -1.42) were associated with decreased sperm count and declined sperm linearity compared with low levels, respectively. Suggestive dose-response relationships were also observed between elevated blood TCM or ∑ THMs (sum of TCM, BDCM, DBCM and TBM) concentration and decreased sperm concentration (both p for trend=0.07), and between elevated blood DBCM concentration and decreased serum total testosterone (p for trend=0.07). Our results indicate that elevated THM exposure may lead to decreased sperm concentration and serum total testosterone. However, the effects of THM exposure on male reproductive health still warrant further studies in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Testosterone treatment is immunosuppressive in superb fairy-wrens, yet free-living males with high testosterone are more immunocompetent.

    OpenAIRE

    Peters, A

    2000-01-01

    The immunocompetence handicap hypothesis proposes that the immunosuppressive effect of testosterone enforces honesty of sexual signalling via a physiological trade-off between signal intensity and immunocompetence. However, evidence that testosterone is immunosuppressive is scant, particularly in birds. I studied the correlation between immunocompetence and testosterone in superb fairy-wrens (Malurus cyaneus), a species with intense intersexual selection. Males are seasonally dichromatic and ...

  15. Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels.

    Science.gov (United States)

    Morgentaler, Abraham; Polzer, Paula; Althof, Stanley; Bolyakov, Alexander; Donatucci, Craig; Ni, Xiao; Patel, Ankur B; Basaria, Shehzad

    2017-09-01

    Although delayed ejaculation (DE) is typically characterized as a persistently longer than anticipated or desired time to ejaculation (or orgasm) during sexual activity, a timing-based definition of DE and its association with serum testosterone has not been established in a large cohort. To examine in an observational study estimated intravaginal ejaculatory latency time (IELT) and masturbatory ejaculation latency time (MELT) in men self-reporting DE, assess the association of IELT and MELT with serum testosterone levels, and determine whether correlation with demographic and sexual parameters exist. Men who resided in the United States, Canada, and Mexico were enrolled from 2011 to 2013. Self-estimated IELT and MELT were captured using an Ejaculatory Function Screening Questionnaire in a sample of 988 men screened for possible inclusion in a randomized clinical trial assessing testosterone replacement therapy for ejaculatory dysfunction (EjD) and who self-reported the presence or absence of DE and symptoms of hypogonadism. Additional comorbid EjDs (ie, anejaculation, perceived decrease in ejaculate volume, and decreased force of ejaculation) were recorded. Men with premature ejaculation were excluded from this analysis. IELT and MELT were compared between men self-reporting DE and men without DE. The associations of IELT and MELT with serum testosterone were measured. IELT, MELT, and total testosterone levels. Sixty-two percent of screened men self-reported DE with or without comorbid EjDs; 38% did not report DE but did report at least one of the other EjDs. Estimated median IELTs were 20.0 minutes for DE vs 15 minutes for no DE (P IELTs and MELTs. Estimated ejaculation times during vaginal intercourse and/or masturbation were not associated with serum testosterone levels in this study; thus, routine androgen evaluation is not indicated in these men. This large systematic analysis attempted to objectively assess the ejaculation latency in men with self

  16. Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

    Science.gov (United States)

    Ponzetto, Federico; Mehl, Florence; Boccard, Julien; Baume, Norbert; Rudaz, Serge; Saugy, Martial; Nicoli, Raul

    2016-01-01

    The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control

  17. Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: a role beyond drug seeking in addiction?

    Science.gov (United States)

    Cruz, F C; Alves, F H F; Leão, R M; Planeta, C S; Crestani, C C

    2013-12-03

    Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic-anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Testosterone Inhibits Trust but Promotes Reciprocity

    NARCIS (Netherlands)

    Boksem, M.A.S.; Mehta, P.H.; Bergh, B. van den; Son, V. van; Trautmann, S.T.; Roelofs, K.; Smidts, A.; Sanfey, A.G.

    2013-01-01

    The steroid hormone testosterone has been associated with behavior intended to obtain or maintain high social status. Although such behavior is typically characterized as aggressive and competitive, it is clear that high social status is achieved and maintained not only through antisocial behavior

  19. Testosterone inhibits trust, but promotes reciprocity

    NARCIS (Netherlands)

    Boksem, M.A.S.; Mehta, P.H.; van den Bergh, B.; van Son, V.; Trautmann, S.T.; Roelofs, K.; Smids, A.; Sanfey, A.G.

    2013-01-01

    The steroid hormone testosterone has been associated with behavior intended to obtain or maintain high social status. Although such behavior is typically characterized as aggressive and competitive, it is clear that high social status is achieved and maintained not only through antisocial behavior

  20. Postnatal Testosterone Concentrations and Male Social Development

    Directory of Open Access Journals (Sweden)

    Gerianne M Alexander

    2014-02-01

    Full Text Available Converging evidence from over 40 years of behavioral research indicates that higher testicular androgens in prenatal life and at puberty contribute to the masculinization of human behavior. However, the behavioral significance of the transient activation of the hypothalamic-pituitary-gonadal (HPG axis in early postnatal life remains largely unknown. Although early research on nonhuman primates indicated suppression of the postnatal surge in testicular androgens had no measurable effects on the later expression of the male behavioral phenotype, recent research from our laboratory suggests that postnatal testosterone concentrations influence male infant preferences for larger social groups and temperament characteristics associated with the later development of aggression. In later assessment of gender-linked behavior in the second year of life, concentrations of testosterone at 3-4 months of age were unrelated to toy choices and activity levels during toy play. However, higher concentrations of testosterone predicted less vocalization in toddlers and higher parental ratings on an established screening measure for autism spectrum disorder. These findings suggest a role of the transient activation of the HPG axis in the development of typical and atypical male social relations and suggest that it may be useful in future research on the exaggerated rise in testosterone secretion in preterm infants or exposure to hormone disruptors in early postnatal life to include assessment of gender-relevant behavioral outcomes, including childhood disorders with sex-biased prevalence rates.

  1. Serum testosterone concentration in chloroquine- treated rats ...

    African Journals Online (AJOL)

    ONOS

    2010-07-05

    Jul 5, 2010 ... The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2.

  2. Body weight, scrotal circumference and testosterone concentration ...

    African Journals Online (AJOL)

    The aim of this study was to compare testosterone concentration, body weight, scrotal circumference and age to penis detachment from days 30 to 240 in young Boer goat males (n = 22) born during the dry (n = 11) and the rainy (n = 11) seasons. In the dry season the parameters varied as follows: body weight from 3.7 ± 1.1 ...

  3. Serum testosterone concentration in chloroquinetreated rats: effects ...

    African Journals Online (AJOL)

    The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2 ml/kg of normal ...

  4. Testosterone acts as a prohormone to stimulate male copulatory behavior in male deer mice (peromyscus maniculatus bairdi).

    Science.gov (United States)

    Clemens, L G; Pomerantz, S M

    1982-02-01

    In order to determine the importance of reduced and aromatized metabolites of testosterone for male sexual behavior in Peromyscus maniculatus bairdi, castrated males were treated with 5 alpha-reductase and aromatase inhibitors. In the first experiment, testosterone propionate (TP) activation of male copulatory behavior was blocked by the administration of the 5 alpha-reductase inhibitor 4-androsten-3-one-17-beta carboxylic acid (17 beta C). These treatments also prevented TP stimulation of seminal vesicles and ventral prostate gland weight. The inhibitory effects of 17 beta C were specific to testosterone, since 17 beta C did not prevent dihydrotestosterone propionate (DHTP) induction of male sexual behavior or seminal vesicles and ventral prostate gland weight increases. In the second experiment, TP activation of male copulatory behavior was prevented by the administration of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). The ATD did not interfere with DHTP activation of male reproductive behavior. Also, TP and DHTP stimulation of accessory sex organ weight was not blocked by ATD. On the basis of these data, it is suggested that metabolism of testosterone to both 5 alpha-reduced androgens and estrogens is obligatory for testosterone to reliably stimulate male sexual behavior in castrated male deer mice.

  5. Deleterious effects of endogenous and exogenous testosterone on mesenchymal stem cell VEGF production.

    Science.gov (United States)

    Ray, Rinki; Herring, Christine M; Markel, Troy A; Crisostomo, Paul R; Wang, Meijing; Weil, Brent; Lahm, Tim; Meldrum, Daniel R

    2008-05-01

    Modulating the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) may be important for the treatment of ischemic myocardial tissue. In this regard, endogenous estrogen may enhance BMSC vascular endothelial growth factor (VEGF) production. However, little information exists regarding the effect of testosterone on stem cell function. We hypothesized that 1) endogenous or exogenous estrogen will enhance stem cell production of VEGF and 2) endogenous or exogenous testosterone will inhibit BMSC VEGF production. BMSCs were collected from adult male, female, castrated male, and ovariectomized female rats. One hundred thousand cells were incubated with testosterone (1, 10, or 100 nM) or estrogen (0.15, 1.5, or 15 nM) for 48 h. Cell supernatants were collected, and VEGF was measured by ELISA. BMSCs harvested from castrated males, normal females, and ovariectomized females produced more VEGF compared with normal males. Castration was associated with the highest level (1,018 +/- 98.26 pg/ml) of VEGF production by BMSCs, which was significantly more than that produced by BMSCs harvested from normal male and normal female animals. Exogenous testosterone significantly reduced VEGF production in BMSCs harvested from ovariectomized females in a dose-dependent manner. Exogenous estrogen did not alter BMSC VEGF production. These findings suggest that testosterone may work on BMSCs to decrease protective growth factor production and that effective removal of testosterone's deleterious effects via castration may prove to be beneficial in terms of protective factor production. By manipulating the mechanisms that BMSCs use to produce growth factors, we may be able to engineer stem cells to produce maximum growth factors during therapeutic use.

  6. Serum testosterone levels of HbSS (sickle cell disease male subjects in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Adediran Adewumi

    2011-08-01

    Full Text Available Abstract Background Infertility is a major problem in sickle cell disease patients, especially in males. In addition to low serum testosterone, other abnormalities involving the accessory sex organs, such as the seminal vesicles and the prostate gland, as well as marked decrease in ejaculate volume may be observed in male HbSS patients. Hence, the need to study the role of sex hormones as a cause of infertility in male HbSS patients. Methods An unmatched case-control study was performed using seventy-five consenting subjects from Lagos University Teaching Hospital. These included 47 patients with haemoglobin phenotype SS from the Sickle cell clinic and 28 volunteered medical students and members of staff with haemoglobin phenotype AA. Demographic data were obtained using a self-administered questionnaire. A total of 5 mls of blood was collected from each subject between 9.00 am & 11.am, and assayed for serum testosterone concentration. Results The concentrations of serum testosterone in HbSS patients ranged from 0.2 to 4.3 ng/ml with a mean of 1.28 ± 0.72 ng/ml whilst the values in HbAA controls ranged from 1.2 to 6.9 ng/ml with a mean of 2.63 ± 1.04 ng/ml. Seven (25.0% of the 28 controls had serum testosterone concentration lower than the quoted reference (normal range whereas 44 (93.6% of the 47 HbSS subjects had serum testosterone concentration lower than the reference range. Conclusion Overall, subjects with HbSS have significantly lower mean serum testosterone than HbAA controls.

  7. Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway.

    Science.gov (United States)

    He, Ze; Sun, Qin; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yun, Shi-Feng; Yao, Bing

    2016-01-01

    This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR), P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l-1 ) for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.

  8. Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway

    Directory of Open Access Journals (Sweden)

    Ze He

    2016-01-01

    Full Text Available This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR, P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD, 17β-hydroxysteroid dehydrogenase (17β-HSD, and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l−1 for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P < 0.05. Thus, ERK1/2 signaling is involved in the roles of annexin A5 in mediating testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.

  9. Testosterone affects song modulation during simulated territorial intrusions in male black redstarts (Phoenicurus ochruros.

    Directory of Open Access Journals (Sweden)

    Beate Apfelbeck

    Full Text Available Although it has been suggested that testosterone plays an important role in resource allocation for competitive behavior, details of the interplay between testosterone, territorial aggression and signal plasticity are largely unknown. Therefore, we investigated if testosterone acts specifically on signals that communicate the motivation or ability of individuals to engage in competitive situations in a natural context. We studied the black redstart, a territorial songbird species, during two different life-cycle stages, the early breeding phase in spring and the non-breeding phase in fall. Male territory holders were implanted with the androgen receptor blocker flutamide (Flut and the aromatase inhibitor letrozole (Let to inhibit the action of testosterone and its estrogenic metabolites. Controls received a placebo treatment. Three days after implantation birds were challenged with a simulated territorial intrusion (STI. Song was recorded before, during and after the challenge. In spring, both treatment groups increased the number of elements sung in parts of their song in response to the STI. However, Flut/Let-implanted males reacted to the STI with a decreased maximum acoustic frequency of one song part, while placebo-implanted males did not. Instead, placebo-implanted males sang the atonal part of their song with a broader frequency range. Furthermore, placebo-, but not Flut/Let-implanted males, sang shorter songs with shorter pauses between parts in the STIs. During simulated intrusions in fall, when testosterone levels are naturally low in this species, males of both treatment groups sang similar to Flut/Let-implanted males during breeding. The results suggest that song sung during a territorial encounter is of higher competitive value than song sung in an undisturbed situation and may, therefore, convey information about the motivation or quality of the territory holder. We conclude that testosterone facilitates context-dependent changes

  10. Association of Free Testosterone With Hypogonadal Symptoms in Men With Near-normal Total Testosterone Levels.

    Science.gov (United States)

    Ramasamy, Ranjith; Golan, Ron; Wilken, Nathan; Scovell, Jason M; Lipshultz, Larry I

    2015-08-01

    To investigate the association between hypogonadal symptoms and free testosterone (FT) levels in men with near-normal total testosterone (T) levels (250-350 ng/dL) and to determine whether a discriminatory threshold for FT exists below which hypogonadal symptoms become more prevalent. We reviewed the charts of 3167 men who presented to an outpatient men's health clinic. Two hundred thirty-one men had symptoms of "low testosterone" and serum testosterone levels between 250 and 350 ng/dL. We evaluated hypogonadal symptoms using the Androgen Deficiency in the Adult Male (ADAM) and quantitative ADAM (qADAM) questionnaires. Serum levels of T and sex hormone-binding globulin were collected on the same day that men completed their questionnaires. We used linear regression to determine whether a threshold of FT exists for hypogonadal symptoms. We performed univariate and multivariable analyses to evaluate factors that predicted a low FT level. The median age was 43.5 years, and the median testosterone and FT levels were 303 ng/dL and 6.3 ng/dL, respectively. Prevalence and severity of hypogonadal symptoms (ADAM and qADAM) were similar between men with low (testosterone levels. Symptom-specific FT thresholds could not be defined, as age remains an important confounder. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Prevalence of undiagnosed testosterone deficiency in aging athletes: does exercise training influence the symptoms of male hypogonadism?

    Science.gov (United States)

    Di Luigi, Luigi; Sgrò, Paolo; Fierro, Valentina; Bianchini, Serena; Battistini, Giancarlo; Magini, Valter; Jannini, Emmanuele A; Lenzi, Andrea

    2010-07-01

    Worldwide many aging males practice sports. A high prevalence of late-onset male hypogonadism has been observed in general population. Sport-participation influences the neuroendocrine system and may decrease serum testosterone. This preliminary study was designed to estimate the prevalence and the symptoms of undiagnosed testosterone deficiency in aging athletes. This observational survey was performed in 183 caucasian male athletes >50 years, in the setting of pre-participation screening. Pituitary-gonadal hormones and symptoms of hypogonadism were investigated. Serum total testosterone (TT), sex hormone binding globulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), free-T4, and thyroid stimulation hormone (TSH) were assayed, and free T, bioactive T, and the LH/TT ratio were calculated. The International Index of Erectile Dysfunction (IIEF-15) and the Center for Epidemiological Studies Depression Scale (CES-D) were administered. Hypogonadal athletes were compared with eugonadal athletes as controls. Prevalence and clinical symptoms of severe (TT 70 years (27.5% and 25.0%, respectively). TT did not correlate with age, training duration, or questionnaire scores. No differences were observed for nonspecific symptoms of hypogonadism, IIEF-15 and CES-D scores between eugonadal and severe hypogonadal athletes. Independently of its etiology, a significant percentage of aging athletes had undiagnosed testosterone deficiency. In a relevant number of these cases, testosterone deficiency was not overtly symptomatic. Our results suggest that sport-participation per se can influence the symptoms of hypogonadism. The history of clinical symptoms may be inaccurate to diagnose testosterone deficiency in aging athletes. Future research should address the clinical relevance and the specific risks of testosterone deficiency in aging athletes, and the need of a systematic pre-participation serum testosterone evaluation.

  12. Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

    Science.gov (United States)

    Goetz, Laura G; Mamillapalli, Ramanaiah; Devlin, Maureen J; Robbins, Amy E; Majidi-Zolbin, Masoumeh; Taylor, Hugh S

    2017-11-01

    Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency. Copyright © 2017 the American Physiological Society.

  13. Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies.

    Science.gov (United States)

    Neto, Walter Krause; Gama, Eliane Florencio; Rocha, Leandro Yanase; Ramos, Carla Cristina; Taets, Wagner; Scapini, Katia Bilhar; Ferreira, Janaina B; Rodrigues, Bruno; Caperuto, Érico

    2015-02-01

    The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the meta-analysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, 1.61-1.69) to 6.20 (95 % CI, 5.22-7.18) kg, although it was heterogeneous (I (2) = 98 %). Effect estimate was 3.59 [2.38-4.81]. Androgen therapy decreased fat mass; effect estimate was -1.78 [-2.57, -0.99] that analysis had also a high level of heterogeneity (I (2) = 81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.

  14. Genetic determinants of serum testosterone concentrations in men.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    2011-10-01

    Full Text Available Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871 and two de novo replication cohorts (n = 4,620 to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG locus (17p13-p12 were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41 and rs6258, p = 2.3×10(-22. Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16. The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01. Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

  15. Long-term Safety of Testosterone and Growth Hormone Supplementation: A Retrospective Study of Metabolic, Cardiovascular, and Oncologic Outcomes.

    Science.gov (United States)

    Ginzburg, Enrique; Klimas, Nancy; Parvus, Chad; Life, Jeff; Willix, Robert; Barber, Michale J; Lin, Alvin; Comite, Florence

    2010-08-18

    Clinical research into the effects of hormonal supplementation has tended to focus on beneficial changes in anthropometric measures. There are fewer data on long-term safety with extended hormonal supplementation. As part of a retrospective database survey, clinical outcomes were tabulated among patients who received at least 1 year of testosterone and/or growth hormone (GH) supplementation. In patients who were treated for at least 2 years, changes in markers of glucose and lipid metabolism were analyzed with and without concomitant use of oral hypoglycemics and statins. In 263 patients (mean age 56) treated for at least 2 years, the only statistically significant effect on markers of glucose metabolism was an increase in glycated hemoglobin (still within normal limits) in patients receiving GH alone or in combination with testosterone but without oral hypoglycemics; with or without hypoglycemics, insulin levels showed no significant change. The only significant effects on markers of lipid metabolism were decreases in total cholesterol and low-density lipoprotein (LDL) in patients receiving combined testosterone and GH without statins. Decreases in LDL were significant in both the statin and non-statin groups; decreases in triglycerides were significant only in the statin group. In 531 patients treated for at least 1 year (mean age 54), the overall incidence of adverse clinical outcomes (prostate disease, diabetes, cardiovascular disease, cancer) was 1.3%. In this retrospective survey, extended testosterone and/or GH supplementation did not adversely affect metabolic markers or clinical outcomes. Safety; Testosterone; Growth hormone; Supplementation.

  16. Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1-42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus.

    Science.gov (United States)

    Li, Q; Zhao, H F; Zhang, Z F; Liu, Z G; Pei, X R; Wang, J B; Li, Y

    2009-10-20

    The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset of learning and memory deficits along with spontaneous overproduction of soluble beta-amyloid peptide (Abeta) in the brain. In our study, 4 month old male SAMP8 mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months. We found that a supplementation with 0.05% or 0.1% GTC prevented spatial learning and memory impairments of mice in the Morris water maze. Better performance of GTC-treated mice was associated with decreased levels of Abeta(1-42) oligomers in the hippocampus. The activity of the protein kinase A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular targets of Abeta oligomers which is crucial for late long-term potentiation and long-term memory formation, was significantly increased after GTC administration. We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions of three representative proteins of synaptic function and synaptic structure, including brain-derived neurotrophic factor(BDNF), post-synaptic density protein-95 (PSD95) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent spatial learning and memory decline of SAMP8 mice by decreasing Abeta(1-42) oligomers and upregulating synaptic plasticity-related proteins in the hippocampus.

  17. Correlation between fennel- or anise-oil administration and damage ...

    African Journals Online (AJOL)

    ... the boundaries of the nuclear membrane and cytoplasmic vacuoles of various ... distribution of heterochromatin in the inner surface and small lipid droplets in the ... besides decreasing testosterone, T3 and T4 hormones and inhibiting sperm ...

  18. The testosterone metabolism of the estuarine invertebrate Neomysis integer (Crustacea: Mysidacea): Identification of testosterone metabolites and endogenous vertebrate-type steroids

    OpenAIRE

    Verslycke, T.; De Wasch, K.; De Brabander, H.F.; Janssen, C.R.

    2002-01-01

    Testosterone metabolism by Neomysis integer (Crustacea; Mysidacea) was assessed to obtain initial data on its metabolic capacity. N. integer were exposed to both testosterone and [14]testosterone. Identification of testosterone metabolites and endogenous steroids was performed using thin-layer chromatography and liquid chromatography with multiple mass spectrometry. Endogenous production of testosterone in mysids was detected for the first time. N. integer were exposed to testosterone and met...

  19. The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF-I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population

    NARCIS (Netherlands)

    Janssen, JAMJL; Huizenga, NATM; Stolk, RP; Grobbee, DE; Pols, HAP; de Jong, FH; Attanasio, AMF; Blum, WF; Lamberts, SWJ

    OBJECTIVE To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF-I/IGFBP system and leptin levels in healthy elderly humans. METHODS In 209 healthy elderly

  20. Cadmium exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, H. [Kumamoto Univ. (Japan). Faculty of Education; Yamaguchi, S.; Murata, H.; Otagiri, M.; Imamura, Y. [Kumamoto Univ. (Japan). Faculty of Pharmaceutical Sciences

    2002-02-01

    Administration of cadmium (Cd) at a dose of 1.23 mg/kg (2.0 mg/kg as CdCl2) markedly decreased the activity of an enzyme (acetohexamide reductase) catalysing the ketone-reduction of acetohexamide, an oral antidiabetic drug, in liver microsomes of male rats. However, the decreased enzyme activity was increased by repeated treatment with testosterone propionate (TP). When male rats were castrated and TP was given to the castrated ones, a similar decrease and increase, as described above, were observed in the microsomal enzyme activity. Cd exposure to male rats induced haemorrhage and atrophy of the testes and significantly diminished serum testosterone levels. There was no possibility that Cd accumulated in liver microsomes of male rats causing direct inhibition of the microsomal enzyme activity. We conclude that Cd exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity. Cd exposure had no effect on acetohexamide reductase activity in liver cytosol of male rats. (orig.)

  1. Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature.

    Science.gov (United States)

    Rooman, Raoul P A; De Beeck, Lieve Op; Martin, Manou; van Doorn, Jaap; Mohan, Subburaman; Du Caju, Marc V L

    2005-04-01

    Pharmacological doses of estrogens or testosterone are used to limit the final height of girls or boys with constitutional tall stature but the mechanism behind this growth inhibition is still debated. We therefore studied the changes in the circulating components of the insulin-like growth factor (IGF) system during high dose sex steroid therapy. Twenty three girls and twenty boys with constitutional tall stature were treated with 100 microg ethinylestradiol per day or 250 mg testosterone ester every 14 days respectively. In 19 girls and 18 boys, the levels of IGF-I, free IGF-I, IGF-II, acid-labile subunit (ALS) and IGF binding proteins (IGFBP)-2 to -6 were measured before and 3-6 months after the start of therapy (group 1). In 18 girls and 11 boys, samples were collected at the end of therapy and 3 to 6 months afterwards (group 2). Fourteen girls and nine boys belonged to both groups. All parameters were measured by radioimmunoassay or ELISA. Levels of IGF-I were decreased significantly by estrogen treatment but remained unchanged during testosterone treatment. Free IGF-I decreased during estrogen treatment but increased during testosterone therapy. Estrogens increased IGF-II and testosterone reduced it. The important reduction of IGFBP-2 during estrogen therapy is not reproduced by androgen therapy, neither is the stimulation by estrogens of IGFBP-4. IGFBP-3 is not modulated by either sex steroid. We found that IGFBP-6 is up-regulated by testosterone but not by estrogens; the reverse is true for ALS, which increased during estrogen treatment but remained unchanged during testosterone treatment. Our findings demonstrate that androgens and estrogens exert differential effects on the circulating levels of several IGF components.

  2. Blunting of exercise-induced salivary testosterone in elite-level triathletes with a 10-day training camp.

    Science.gov (United States)

    Hough, John; Robertson, Caroline; Gleeson, Michael

    2015-10-01

    This study examined the influence of 10 days of intensified training on salivary cortisol and testosterone responses to 30-min, high-intensity cycling (55/80) in a group of male elite triathletes. Seven elite male triathletes (age 19 ± 1 y, VO2max 67.6 ± 4.5 mL · kg-1 · min-1) completed the study. Swim distances increased by 45%. Running and cycling training hours increased by 25% and 229%, respectively. REST-Q questionnaires assessed mood status before, during, and after the training period. Unstimulated saliva samples were collected before, after, and 30 min after a continuous, high-intensity exercise test. Salivary cortisol and testosterone concentrations were assessed. Compared with pretraining, blunted exercise-induced salivary testosterone responses to the posttraining 55/80 were found (P = .004). The absolute response of salivary testosterone concentrations to the 55/80 decreased pretraining to posttraining from 114% to 85%. No changes were found in exercise-induced salivary cortisol concentration responses to the 55/80. REST-Q scores indicated no changes in the participants' psychological stress-recovery levels over the training camp. The blunted exercise-induced salivary testosterone is likely due to decreased testicular testosterone production and/or secretion, possibly attributable to hypothalamic dysfunction or reduced testicular blood flow. REST-Q scores suggest that the triathletes coped well with training-load elevations, which could account for the finding of no change in the exercise-induced salivary cortisol concentration. Overall, these findings suggest that the 55/80 can detect altered exercise-induced salivary testosterone concentrations in an elite athletic population due to increased training stress. However, this alteration occurs independently of a perceived elevation of training stress.

  3. Involvement of the adrenal glands and testis in gap junction formation via testosterone within the male rat anterior pituitary gland.

    Science.gov (United States)

    Sakuma, Eisuke; Wada, Ikuo; Otsuka, Takanobu; Wakabayashi, Kenjiro; Ito, Kinya; Soji, Tsuyoshi; Herbert, Damon C

    2012-12-01

    We investigated the influence of testicular and adrenal androgens on the presence of gap junctions between folliculo-stellate cells in the anterior pituitary glands of 60-day-old Wistar-Imamichi strain male rats. The animals were separated into six groups: Group A served as the controls and had free access to a normal diet and water, Group B was given a normal diet and 0.9% NaCl for their drinking water as the controls of adrenalectomized groups, Group C was castrated, Group D was adrenalectomized, Group E was both castrated and adrenalectomized, and Group F was also both castrated and adrenalectomized. In addition, the animals of Group F were administered a dose of testosterone that is known to produce high physiological levels of the hormones in plasma. Five rats from each group were sacrificed 1, 2, 3, 4, 5, 6, and 7 days after their respective operation, and the anterior pituitary glands were removed and prepared for observation by transmission electron microscopy. We quantified the number of follicles and gap junctions and calculated the rate of occurrence as the ratio of the number of gap junctions existing between folliculo-stellate cells per intersected follicle profile. Simultaneous removal of adrenal glands with castration resulted in a significantly decrease in the number of gap junctions, whereas the administration of testosterone to these rats compensated for this change. These observations indicate that the preservation of gap junctions between folliculo-stellate cells is mainly dependent on androgens from both the testes and adrenal glands in adult male rats. Copyright © 2012 Wiley Periodicals, Inc.

  4. The TRPM8 Protein Is a Testosterone Receptor

    Science.gov (United States)

    Asuthkar, Swapna; Demirkhanyan, Lusine; Sun, Xiaohui; Elustondo, Pia A.; Krishnan, Vivek; Baskaran, Padmamalini; Velpula, Kiran Kumar; Thyagarajan, Baskaran; Pavlov, Evgeny V.; Zakharian, Eleonora

    2015-01-01

    Testosterone is a key steroid hormone in the development of male reproductive tissues and the regulation of the central nervous system. The rapid signaling mechanism induced by testosterone affects numerous behavioral traits, including sexual drive, aggressiveness, and fear conditioning. However, the currently identified testosterone receptor(s) is not believed to underlie the fast signaling, suggesting an orphan pathway. Here we report that an ion channel from the transient receptor potential family, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-induced rapid actions. Using cultured and primary cell lines along with the purified TRPM8 protein, we demonstrate that testosterone directly activates TRPM8 channel at low picomolar range. Specifically, testosterone induced TRPM8 responses in primary human prostate cells, PC3 prostate cancer cells, dorsal root ganglion neurons, and hippocampal neurons. Picomolar concentrations of testosterone resulted in full openings of the purified TRPM8 channel in planar lipid bilayers. Furthermore, acute applications of testosterone on human skin elicited a cooling sensation. Our data conclusively demonstrate that testosterone is an endogenous and highly potent agonist of TRPM8, suggesting a role of TRPM8 channels well beyond their well established function in somatosensory neurons. This discovery may further imply TRPM8 channel function in testosterone-dependent behavioral traits. PMID:25480785

  5. Testosterone-Related Cortical Maturation Across Childhood and Adolescence

    Science.gov (United States)

    Nguyen, Tuong-Vi; McCracken, James; Ducharme, Simon; Botteron, Kelly N.; Mahabir, Megan; Johnson, Wendy; Israel, Mimi; Evans, Alan C.; Karama, Sherif

    2013-01-01

    Neuroendocrine theories of brain development hold testosterone as the predominant factor mediating sex-specific cortical growth and the ensuing lateralization of hemispheric function. However, studies to date have focussed on prenatal testosterone rather than pubertal changes in testosterone. Yet, animal studies have shown a high density of androgen-sensitive receptors in multiple key cortical areas, and puberty is known to coincide with both a significant rise in testosterone and the emergence of behavioral sex differences, suggesting peripubertal influences of testosterone on brain development. Here, we used linear mixed models to examine sex-specific cortical maturation associated with changes in testosterone levels in a longitudinal sample of developmentally healthy children and adolescents. A significant “sex by age by testosterone” interaction on cortical thickness (CTh) involving widespread areas of the developing brain was found. Testosterone levels were associated with CTh changes in regions of the left hemisphere in males and of the right hemisphere in females. In both sexes, the relationship between testosterone and CTh varied across the age span. These findings show the association between testosterone and CTh to be complex, highly dynamic, and to vary, depending on sex and age; they also suggest sex-related hemispheric lateralization effects of testosterone in humans. PMID:22617851

  6. Physiological levels of testosterone kill salmonid leukocytes in vitro

    Science.gov (United States)

    Slater, C.H.; Schreck, C.B.

    1997-01-01

    Adult spring chinook salmon (Oncorhynchus tshawytscha) elaborate high plasma concentrations of testosterone during sexual maturation, and these levels of testosterone have been shown to reduce the salmonid immune response in vitro. Our search for the mechanism of testosterone's immunosuppressive action has led to the characterization of an androgen receptor in salmonid leukocytes. In the present study we examined the specific effects that testosterone had on salmonid leukocytes. Direct counts of viable leukocytes after incubation with and without physiological levels of testosterone demonstrate a significant loss of leukocytes in cultures exposed to testosterone. At least 5 days of contact with testosterone was required to produce significant immunosuppression and addition of a 'conditioned media' (supernatant from proliferating lymphocytes not exposed to testosterone) did not reverse the immunosuppressive effects of testosterone. These data lead us to conclude that testosterone may exert its immunosuppressive effects by direct action on salmonid leukocytes, through the androgen receptor described, and that this action leads to the death of a significant number of these leukocytes.

  7. Effect of a single injection of testosterone enanthate on 17β estradiol and bone turnover markers in hypogonadal male patients.

    Science.gov (United States)

    Camozzi, V; Bonanni, G; Frigo, A; Piccolo, M; Ferasin, S; Zaninotto, M; Boscaro, M; Luisetto, G

    2015-04-01

    Several clinical studies testify the critical role played by estrogens in male bone metabolism. The aim of our study is to assess the effect of a single injection of testosterone enanthate in a group of hypogonadal men on 17β estradiol serum levels and some bone metabolic parameters. Twenty-one hypogonadal males were given one testosterone enanthate injection (250 mg). Blood samples were drawn before the injection and after 1, 2 and 3 weeks. The following variables were measured: Total testosterone (TT), 17β estradiol (17β E2), Sex hormone binding globulin, total alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen (CTx). After testosterone injection, both TT and 17β E2 increased, peaking 1 week after the injection. Individual observation of the response of 17β E2 to testosterone showed that a subgroup (n = 9) failed to respond with any increase in 17β E2 at any of the weekly tests (group E2-), while the remainder (n = 12) showed a significant increase in 17β E2, which reached a mean value three times higher than at baseline (group E2+). The E2- patients reached a TT peak lower than that observed in the E+ group. CTx serum levels declined progressively in the E2+ group, reaching the significance (p = 0.03) at the end of the study, while it did not change in E- group. This study suggests that a single injection of testosterone might have different effects on the production of endogenous estrogens, and a significant reduction of bone resorption parameters takes place only in the patients who show a significant increase of 17ß estradiol in response to testosterone administration.

  8. Effect of Voluntary Ethanol Consumption Combined with Testosterone Treatment on Cardiovascular Function in Rats: Influence of Exercise Training.

    Directory of Open Access Journals (Sweden)

    Sheila A Engi

    Full Text Available This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6, animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α1-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances.

  9. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice.

    Science.gov (United States)

    MacPherson, Kathryn P; Sompol, Pradoldej; Kannarkat, George T; Chang, Jianjun; Sniffen, Lindsey; Wildner, Mary E; Norris, Christopher M; Tansey, Malú G

    2017-06-01

    Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer's disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII + , CD45 high , and Ly6C high ) myeloid-derived CD11b + immune cells are decreased while CD3 + T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4 + T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD. Immune cells and cytokines perform specialized functions inside and outside the brain to maintain optimal brain health; but the extent to which their activities change in response to neuronal dysfunction and degeneration is not well understood. Our findings indicate that neutralization of s

  10. Effects of gendered behavior on testosterone in women and men.

    Science.gov (United States)

    van Anders, Sari M; Steiger, Jeffrey; Goldey, Katherine L

    2015-11-10

    Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to "sex differences" in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology.

  11. Androgen decreases dopamine neurone survival in rat midbrain.

    Science.gov (United States)

    Johnson, M L; Day, A E; Ho, C C; Walker, Q D; Francis, R; Kuhn, C M

    2010-04-01

    Clinical studies show that men are more likely to develop disorders affecting midbrain dopaminergic pathways, such as drug addiction and Parkinson's disease (PD). Although a great deal of focus has been given to the role of oestrogen in the maintenance of midbrain dopaminergic pathways, little is known about how testosterone influences these pathways. In the present study, we used stereological analysis of tyrosine hydroxylase-immunoreactive (TH-IR) cell bodies to determine how testosterone influences the dopaminergic cell bodies of the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Rats and mice were castrated at postnatal day (PN) 60, and these midbrain cell populations were counted on PN 90. One month after castration, TH-IR cell number had increased in the SNpc and VTA of rats and mice. Replacement with testosterone or the non-aromatisable analogue dihydrotestosterone (DHT) in castrated animals reduced TH-IR cell number in the SNpc and VTA in rats. In mice, the decrease of TH-IR cell number with testosterone or DHT replacement was observed only in the SNpc. The apparent increase in TH-IR neurone number after castration is not explained by an increase in TH expression because the number of nondopaminergic cells (TH-immunonegative, TH-IN) did not decrease proportionally after castration. TH-IN cell number did not change after castration or hormone replacement in rat or mouse SNpc or VTA. These findings suggest that testosterone may play a suppressive role in midbrain dopaminergic pathways.

  12. Light induced degradation of testosterone in waters

    Energy Technology Data Exchange (ETDEWEB)

    Vulliet, Emmanuelle, E-mail: e.vulliet@sca.cnrs.fr [Service Central d' Analyse du CNRS - USR59, Chemin du Canal, F-69360 Solaize (France); Falletta, Marine; Marote, Pedro [Laboratoire des Sciences Analytiques - UMR 5180, Universite Claude Bernard, 43 bd du 11 Novembre 1918, F-69622 Villeurbanne Cedex (France); Lomberget, Thierry [Laboratoire de Chimie Therapeutique, Universite de Lyon, Universite Lyon 1, Faculte de Pharmacie-ISPB, EA 4443 Biomolecules, Cancer et Chimioresistances, INSERM U863 Hormones steroides et proteines de liaison, IFR 62, 8 avenue Rockefeller, F-69373, Lyon Cedex 08 (France); Paisse, Jean-Olivier; Grenier-Loustalot, Marie-Florence [Service Central d' Analyse du CNRS - USR59, Chemin du Canal, F-69360 Solaize (France)

    2010-08-01

    The degradation of testosterone under simulated irradiations was studied in phosphate buffers and in natural waters at various excitation wavelengths. The quantum yield of photolysis was significantly lower at 313 nm (2.4 x 10{sup -3}) than at 254 nm (0.225). The formation of several photoproducts was observed, some of them being rapidly transformed in turn while others show higher stability towards subsequent irradiations. The nature of the main products was tentatively identified, both deduced from their spectral and spectrometric data and by comparison with synthesised standard compounds. Among the obtained photoproducts, the main one is possibly a spiro-compound, hydroxylated derivative of testosterone originating from the photohydratation of the enone group. The photodegradation pathway includes also photorearrangements. One of them leads to (1,5,10)-cyclopropyl-17{beta}-hydroxyandrostane-2-one. The pH of the water does not seem to affect the rate of phototransformation and the nature of the by-products.

  13. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    Directory of Open Access Journals (Sweden)

    Wender Nascimento Rouver

    Full Text Available The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM, castrated (CAST, castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group or supraphysiological dose (2.5 mg/kg/day, SUPRA group of testosterone for 15 days. Systolic blood pressure (SBP was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO, L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT. We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

  14. Annatto tocotrienol improves indices of bone static histomorphometry in osteoporosis due to testosterone deficiency in rats.

    Science.gov (United States)

    Chin, Kok-Yong; Abdul-Majeed, Saif; Fozi, Nur Farhana Mohd; Ima-Nirwana, Soelaiman

    2014-11-10

    This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.

  15. Annatto Tocotrienol Improves Indices of Bone Static Histomorphometry in Osteoporosis Due to Testosterone Deficiency in Rats

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2014-11-01

    Full Text Available This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL, sham (SH, orchidectomized (ORX, annatto tocotrienol-treated (AnTT and testosterone enanthate-treated (TE groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05. Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05. The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.

  16. Testosterone and metabolic syndrome: The link

    Directory of Open Access Journals (Sweden)

    Ranabir Salam

    2012-01-01

    Full Text Available Metabolic syndrome (MetS or "Syndrome X" which is a constellation of insulin resistance, hyperglycemia, hypertension, low high-density lipoprotein cholesterol (HDL-C, and increased very-low-density lipoprotein (VLDL and triglyceride (TG levels. It is one of the main threats for public health in the 21st century with its associated risk of cardiovascular disease. This condition affects a major chunk of mankind. International Diabetes Federation (IDF estimated that around 20-25% of the adult population of the world has MetS. Several definitions have been put forward by different expert bodies leading to confusion. To overcome this, joint new statement of many expert group have been issued. Serum testosterone (T has been shown to be associated with MetS. Several studies have shown a higher prevalence of MetS in subjects with low testosterone. There are also several studies showing a significant difference in serum T between those with MetS and those without. Serum T has also been shown to be associated with components of MetS and testosterone replacement therapy (TRT improves various metabolic and anthropometric parameters in MetS. Patients with androgen deprivation for treatment of various cancers have also been reported to have higher prevalence of MetS. But the evidence of association is not sufficient evidence for the causation of MetS by low testosterone and long-term studies are needed to confirm whether T deficiency is the cause or is a feature of MetS.

  17. Prenatal Testosterone and Preschool Disruptive Behavior Disorders

    OpenAIRE

    Roberts, Bethan A.; Martel, Michelle M.

    2013-01-01

    Disruptive Behaviors Disorders (DBD), including Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD), are fairly common and highly impairing childhood behavior disorders that can be diagnosed as early as preschool. Prenatal exposure to testosterone may be particularly relevant to these early-emerging DBDs that exhibit a sex-biased prevalence rate favoring males. The current study examined associations between preschool DBD symptom domains and prenatal exposu...

  18. Differential maternal testosterone allocation among siblings benefits both mother and offspring in the zebra finch Taeniopygia guttata.

    Science.gov (United States)

    Boncoraglio, Giuseppe; Groothuis, Ton G G; von Engelhardt, Nikolaus

    2011-07-01

    Parents are selected to preferentially invest in the offspring with highest reproductive value. One mechanism for achieving this is the modification of competitive asymmetries between siblings by maternal hormones. In many organisms, offspring value varies according to birth position in the brood, which determines survival chances and competitive advantage over access to resources. In birds, variation in yolk androgen allocation over the laying sequence is thought to modulate dominance of senior chicks over junior brood mates. We tested this hypothesis in zebra finches, which show a naturally decreasing pattern of within-clutch testosterone allocation. We abolished these within-clutch differences by experimentally elevating yolk testosterone levels in eggs 2-6 to the level of egg 1, and we assessed fitness measures for junior offspring (eggs 2-6), senior offspring (egg 1), and their mothers. Testosterone-injected eggs hatched later than control eggs. Junior, but not senior, chicks in testosterone-treated broods attained poorer phenotypic quality compared to control broods, which was not compensated for by positive effects on seniors. Mothers were generally unaffected by clutch treatment. Thus, naturally decreasing within-clutch yolk testosterone allocation appears to benefit all family members and does not generally enhance brood reduction by favoring senior chicks, in contrast to the widely held assumption.

  19. Effect of Radiation Leakage of Microwave Oven on Rat Serum Testosterone at Pre and Post Pubertal Stage

    Directory of Open Access Journals (Sweden)

    Y Zare

    2008-01-01

    Full Text Available Introduction: Since discovery of high frequency waves, their biological effects have been in great attention. Increased male fertility problems proposed their possible relation to use of microwaves. Testes are of very active body tissues, which can be affected by these waves. Age of exposure may also be an important factor. Methods: This study was carried out to evaluated testosterone level in rats exposed to microwave radiation at pre and post puberty. For this study 18 adult (2 month old and 18 immature (1 month old male rats were selected and each group divided in two groups, control and test group. Test groups were exposed to 2450 MHZ microwaves produced by microwave oven (LG Brant, three times a day, 30 minute each time. Control groups were kept in laboratory at same temperature and light condition. After 60 days blood was collected by heart puncture and testosterone was measured in serum by RIA method. Mean testosterone levels were compared by T-test. Result: The results showed that in immature group testosterone has not changed significantly compare to control group; however in adult group this value was significantly decreased in test group in comparison with control (P<0.005. Conclusion: exposure to microwaves leakage of microwave oven decreased testosterone in adult male rats, which may be due to its direct effect on Leydig cells or indirectly through its effect on pituitary and hypothalamus.

  20. The TRPM8 protein is a testosterone receptor: II. Functional evidence for an ionotropic effect of testosterone on TRPM8.

    Science.gov (United States)

    Asuthkar, Swapna; Demirkhanyan, Lusine; Sun, Xiaohui; Elustondo, Pia A; Krishnan, Vivek; Baskaran, Padmamalini; Velpula, Kiran Kumar; Thyagarajan, Baskaran; Pavlov, Evgeny V; Zakharian, Eleonora

    2015-01-30

    Testosterone is a key steroid hormone in the development of male reproductive tissues and the regulation of the central nervous system. The rapid signaling mechanism induced by testosterone affects numerous behavioral traits, including sexual drive, aggressiveness, and fear conditioning. However, the currently identified testosterone receptor(s) is not believed to underlie the fast signaling, suggesting an orphan pathway. Here we report that an ion channel from the transient receptor potential family, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-induced rapid actions. Using cultured and primary cell lines along with the purified TRPM8 protein, we demonstrate that testosterone directly activates TRPM8 channel at low picomolar range. Specifically, testosterone induced TRPM8 responses in primary human prostate cells, PC3 prostate cancer cells, dorsal root ganglion neurons, and hippocampal neurons. Picomolar concentrations of testosterone resulted in full openings of the purified TRPM8 channel in planar lipid bilayers. Furthermore, acute applications of testosterone on human skin elicited a cooling sensation. Our data conclusively demonstrate that testosterone is an endogenous and highly potent agonist of TRPM8, suggesting a role of TRPM8 channels well beyond their well established function in somatosensory neurons. This discovery may further imply TRPM8 channel function in testosterone-dependent behavioral traits. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Food, stress, and circulating testosterone: Cue integration by the testes, not the brain, in male zebra finches (Taeniopygia guttata).

    Science.gov (United States)

    Lynn, Sharon E; Perfito, Nicole; Guardado, Daisy; Bentley, George E

    2015-05-01

    Food abundance is closely associated with reproductive readiness in vertebrates. Food scarcity can activate the hypothalamo-pituitary-adrenal axis, decrease sex steroid secretion, and dampen reproductive behavior. However, the mechanisms underlying these transient effects are unclear. Gonadotropin inhibitory hormone (GnIH), a neuropeptide present in the brain and gonads, is also influenced by glucocorticoids and fasting in some species. We investigated whether fasting stress activated the GnIH system in zebra finches (Taeniopygia guttata), with the potential for downstream effects on reproductive physiology and behavior. We fasted or fed males ad libitum for 10h. Fasting increased corticosterone and decreased testosterone in circulation. To assess whether the decrease in testosterone was mediated by changes in the hypothalamus and/or the gonads, we (1) quantified GnRH- and GnIH-positive neurons in the hypothalamus, (2) assessed hypothalamic gene expression for GnRH and GnIH, and (3) examined gene expression for proteins involved in testosterone synthesis in fasted and control birds. No measure of hypothalamic neuropeptides was related to treatment or circulating steroids. However, birds with higher corticosterone had higher testicular GnIH expression and lower testosterone. StAR and LHR expression were lower in the testes of fasted birds than controls. Thus, the decrease in testosterone was not likely mediated by hypothalamic GnIH, but rather by direct actions of fasting and/or corticosterone on the testes, indicating that the testes can integrate and respond to cues of stress directly. Such local inhibition of testosterone synthesis may allow for rapid and reversible changes in physiology and behavior when conditions are inappropriate for breeding. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Changes in masculine sexual behavior, corticosterone and testosterone in response to acute and chronic stress in male rats.

    Science.gov (United States)

    Retana-Márquez, S; Bonilla-Jaime, H; Vázquez-Palacios, G; Martínez-García, R; Velázquez-Moctezuma, J

    2003-11-01

    Chronic exposure to stressors increases HPA axis activity and concomitantly reduces HPG axis activity. This antagonistic relationship between both these axes has been proposed to underlie the inhibition of reproductive function due to stress. Sexual behavior in males may be the most vulnerable aspect of male reproduction to acute and chronic stress and it has been suggested that alterations in sexual behavior during stress are due to the antagonistic relationship between testosterone and corticosteroids. However, only in a few studies has a correlation between the levels of testosterone and corticosterone, and sexual behavior been made. In this study, we evaluated the effects of different stressors, applied both acute and chronically, on masculine sexual behavior and whether or not these effects on sexual behavior are accompanied by changes in plasma levels of corticosterone and testosterone. Additionally, we evaluated the effect of testosterone treatment on the effects of stress on sexual behavior. Sexually experienced male rats were exposed to one of the following stressors: immobilization (IMB), electric foot shocks (EFS) or immersion in cold water (ICW). Sexual behavior and plasma levels of testosterone and corticosterone were assessed on days 1, 5, 10, 15, and 20 of stress. In a second experiment, males were castrated, treated with 3 different doses of testosterone propionate (TP) and exposed to ICW for 20 consecutive days. Sexual behavior was assessed on days 1, 5, 10, 15, and 20 and steroids were evaluated on day 20. Parameters of masculine sexual behavior were modified depending on the characteristics of each stressor. Mount, intromission and ejaculation latencies increased significantly, the number of mounts increased, and ejaculations decreased significantly in males exposed to EFS and to ICW but not in males exposed to IMB. Associated with these effects, testosterone decreased in the EFS and ICW groups on days 1, 15, and 20. However, corticosterone

  3. Oxytocin, testosterone, and human social cognition.

    Science.gov (United States)

    Crespi, Bernard J

    2016-05-01

    I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint

  4. Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids.

    Science.gov (United States)

    Santiago-Moreno, J; Gómez-Brunet, A; Toledano-Díaz, A; Salas-Vega, R; Gómez-Guillamón, F; López-Sebastián, A

    2012-08-01

    This work examines the effect of testosterone secretion and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex (Capra pyrenaica), here used as a model for polygynous wild bovids. The hypothesis that high levels of testosterone provide an endocrine signal that inhibits horn growth in autumn was tested by assessing the effect of cyproterone acetate (CA), an anti-androgen, administered in October - coinciding with the period of natural increases in plasma testosterone concentrations - under different photoperiodic conditions (natural photoperiod and artificial long days). The persistence of horn growth during autumn in all ibexes held under the long-day photoperiodic conditions clearly shows that horn growth regulation in the mating season is primarily modulated by day length and not by a fall in testosterone concentration. A retrospectively designed second experiment involving testosterone propionate (TP) administration in April (when horns are growing) was then undertaken to confirm that high levels of testosterone do not inhibit horn growth. Overall, the results strongly suggest that the rise in testosterone secretion during the autumn mating season does not act as an endocrine signal for the arrest of horn growth, although the rate of horn growth before the mating season may be related to springtime testosterone levels. A direct relationship was seen between the rate of horn growth and the incidence of sperm abnormalities. Neither CA treatment in October nor TP administration in April affected the studied sperm variables. By contrast, CA treatment plus artificial long days in autumn had a negative effect on sperm motility and sperm morphology.

  5. Ameliorative effects of stinging nettle (Urtica dioica) on testosterone-induced prostatic hyperplasia in rats.

    Science.gov (United States)

    Nahata, A; Dixit, V K

    2012-05-01

    The present study investigated the effects of stinging nettle (Urtica dioica L.) (UD) on benign prostatic hyperplasia (BPH) induced by testosterone. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of UD. Two biochemical markers viz., β-sitosterol and scopoletin, were isolated and characterised in the extracts utilising High-performance thin layer chromatographic, FTIR, NMR and overlain UV spectral studies. Hyperplasia was induced in rats by subcutaneous administration of testosterone (3 mg kg(-1) s.c.) for 28 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether and ethanolic extracts (10, 20 and 50 mg kg(-1) p.o.) and isolated β-sitosterol (10 and 20 mg kg(-1) p.o.) was undertaken. Finasteride was used as a positive control (1 mg kg(-1) p.o.). Measurement of prostate/body weight ratio, weekly urine output and serum testosterone levels, prostate-specific antigen levels (on day 28) and histological examinations carried out on prostates from each group led us to conclude that UD can be used as an effective drug for the management of BPH. © 2011 Blackwell Verlag GmbH.

  6. Testosterone Regulates Tight Junction Proteins and Influences Prostatic Autoimmune Responses

    OpenAIRE

    Meng, Jing; Mostaghel, Elahe A.; Vakar-Lopez, Funda; Montgomery, Bruce; True, Larry; Nelson, Peter S.

    2011-01-01

    Testosterone and inflammation have been linked to the development of common age-associated diseases affecting the prostate gland including prostate cancer, prostatitis, and benign prostatic hypertrophy. We hypothesized that testosterone regulates components of prostate tight junctions which serve as a barrier to inflammation, thus providing a connection between age- and treatment-associated testosterone declines and prostatic pathology. We examined the expression and distribution of tight jun...

  7. The relationship between sleep disorders and testosterone in men.

    Science.gov (United States)

    Wittert, Gary

    2014-01-01

    Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH) secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG), or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA) appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP) does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.

  8. The relationship between sleep disorders and testosterone in men

    Directory of Open Access Journals (Sweden)

    Gary Wittert

    2014-04-01

    Full Text Available Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG, or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.

  9. Relationship between sperm count, serum gonadotropins and testosterone levels in normo-, oligo- and azoospermia.

    Science.gov (United States)

    Lenau, H; Gorewoda, I; Niermann, H

    1980-01-01

    In 92 men with normozoospermia (greater than 40 X 10(6)/ml), 105 with slight oligozoospermia (greater than 10 X 10(6)/ml), 100 with severe oligozoospermia (less than 10 X 10(6)/ml) and 56 with azoospermia, serum testosterone, LH and FSH were measured radioimmunologically. With an increasing degree of reduction of spermatozoa, a decreasing testosterone level and increasing LH and FSH levels could be demonstrated. In normozoospermia, between 40 and 140 X 10(6)/ml, a direct correlation was found between FSH and sperm count, and, in the group between 40 and 100 X 10(6)/ml, a direct correlation between T and sperm count. A disturbed LH:T balance is often observed which beside decreased serum T levels demonstrates a testicular deficiency in androgen production.

  10. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: I. Endocrine effects.

    Science.gov (United States)

    Zimmerman, Y; Foidart, J-M; Pintiaux, A; Minon, J-M; Fauser, B C J M; Cobey, K; Coelingh Bennink, H J T

    2015-02-01

    Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34 kg/m²), a COC containing 30mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Δ4-androstenedione (AD), 3α-androstanediol glucuronide (ADG) and estradiol (E₂) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period -- 1.3±1.2 nmol/L vs. 0.0±0.4 nmol/L; pFree T and the FTI increased significantly (pfree T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (pfree T levels were restored by only 47% as most of the T remains bound to SHBG. When using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is insufficient to normalize free T levels completely. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Pengaruh Latihan Fisik Teratur terhadap Kadar Glukosa Darah dan Hubungannya dengan Kadar Testosteron Total pada Tikus Model Diabetes

    Directory of Open Access Journals (Sweden)

    Zulkarnain

    2015-03-01

    Full Text Available A state of chronic hyperglycemia in diabetes mellitus may cause dysfunction of the reproductive system; one of these is the decrease in total testosterone level. A regular physical exercise is one of the non-pharmacological approaches to reduce blood glucose level and impr