Blood Testosterone Concentrations Research Articles

Initial characterization of an outbreed mouse model for male factor (in)fertility

We analysed an outbreed mouse line which was selected for the phenotype 'high fertility' for 158 generations. During this selection period the mouse strain increased the number of offspring per litter from 10.4 to 17.1 and the total litter weight up to ~160%. In this study, we initially characterize the reproductive phenotype of high fertility males. Surprisingly, male bucks of the fertility line (FL1) show reduced percentage of motile and progressive motile spermatozoa; however, other sperm motility characteristics (e.g. velocity parameters) are improved compared with an unselected control line. Cytometrical investigation of the testicular cell-type composition indicated a significant increased concentration of diploid cells by a concomitant reduction in haploid cells in the testicular parenchyma of FL1. Furthermore, total testosterone concentrations in blood are dramatically increased in FL1 (>20ng/mL). In line with increased testosterone levels, we observed increased expression rates of steroidogenic key enzymes Cyp11 and Cyp17 from FL1 testis samples. These data indicate that FL1 males have a manifest 'high fertility phenotype'. Diallelic crosses imply that male-only contribution largely determines the reproductive outcome in cross-breeding experiments. FL1 therefore is a promising model for future investigations on male factor (in)fertility. Our observation might also offer valuable cues for human reproductive medicine.

Antifertility Activity of Ethanolic Seed Extract of Celery ( Apium Graveolens L. ) in Male Albino Rats

Objectives:This study was aimed at evaluating the effect of ethanolic seed extract of Apium graveolens L. (Apiaceae)(ESEAG) on male rat fertility.Methods:Two doses of the extract (425 and 213 mg/kg body weight) were administered by oral gavage for sixty consecutive days. Five days before the end of this period, each rat was cohabited with two female rats. Fertility indices, hematology, and organ weight and histology were then assessed. Results:The ESEAG arrested spermatogenesis and caused a marked, dose-dependent decrease in sperm count, cauda epididymal sperm motility, blood testosterone concentration, weight of testes and seminal vesicles, testicular protein contentas well as diameter and viability of seminiferous tubules.In addition, a lower number and weight of viable fetuses was obtained for female rats which were impregnated by ESEAG-treated male rats. Hematological parameters, serum liver enzyme levels, thyroid weight and liver and kidney histoarchitecture were not affected. Conclusion:This study shows a dose-dependent antifertility effect of the ESEAG in male rats without toxic effects on other body organs.

Suplementação de touros com sabões cálcicos de ácidos graxos poli-insaturados e qualidade seminal pré e pós-congelação

The objective of this experiment was to evaluate semen quality of bulls supplemented with calcium soaps of fatty acids polyunsaturated. Twenty Angus, Brangus, Hereford and Braford bulls were randomly allocated into two groups, each with ten animals. Each group received a diet consisting of forage, commercial ration, mineral supplements and supplement. Two supplements types were evaluated: functional supplement, with fatty acids polyunsaturated (PUFA) incorporation or energy supplement, with cassava meal (Manihot esculenta, Crantz) incorporation. During trial period the semen quality was evaluated using routine test (volume, concentration, mass motility, individual motility, sperm morphology) and complementary test: (hypo-osmotic test, giemsa/tripan-azul coloration and thermotolerance test). The semen of group bulls supplemented with commercial calcium soaps of PUFA (Megalac-E®) showed greater sperm motility (83.3% vs. 75.3%), percentage of sperm with intact acrosome (94.8% vs. 91.8%) and percentage of sperm with intact plasma membrane (98.0% vs. 96.6%) when compared with semen of group bulls supplemented with cassava (P<0.05). The supplement type did not affect semen volume, sperm concentration and testosterone concentration in blood (P>0.05). There were interactions between treatment and collection period for percentage of normal sperm and percentage of spermatozoa with hypo-osmotic positive test (P<0.05). The type of supplement did not affect sperm motility, the hypo-osmotic test and fast thermotolerance test after thawing (P>0.05). PUFA calcium soaps supplementation increased percentage of spermatozoa with plasma membrane integrity (51.5 vs. 42.2%) and spermatozoa intact acrosome (48.0% vs. 39.2%) after thawing.

2128 HIGH TESTOSTERONE LEVELS IN PROSTATE TISSUE OBTAINED BY NEEDLE BIOPSY CORRELATE WITH POOR PROGNOSIS FACTORS IN PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Markers (I)1 Apr 20132128 HIGH TESTOSTERONE LEVELS IN PROSTATE TISSUE OBTAINED BY NEEDLE BIOPSY CORRELATE WITH POOR PROGNOSIS FACTORS IN PROSTATE CANCER PATIENTS Yasuhide Miyoshi, Susumu Umemoto, Uemura Hiroji, Seijiro Honma, Yasuhiro Shibata, and Yohinobu Kubota Yasuhide MiyoshiYasuhide Miyoshi Yokohama, Japan More articles by this author , Susumu UmemotoSusumu Umemoto Yokohama, Japan More articles by this author , Uemura HirojiUemura Hiroji Yokohama, Japan More articles by this author , Seijiro HonmaSeijiro Honma Kawasaki, Japan More articles by this author , Yasuhiro ShibataYasuhiro Shibata Maebashi, Japan More articles by this author , and Yohinobu KubotaYohinobu Kubota Yokohama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2037AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There has been no consensus on the prostatic tissue and blood androgen concentrations in men with different stages and pathological grades of prostate cancer. In this study, testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy specimens of prostate were examined by newly developed ultra sensitive LC-MS/MS method. METHODS We analyzed 196 men (mean age 70.6 years) diagnosed as prostate cancer from November 2005 to July 2007. Those patients received systematic needle biopsy, and additionally one needle biopsy from proximal zone was conducted for the purpose of simultaneous determination of T and DHT. T and DHT concentrations in prostate tissues and blood were determined by LC-MS/MS method. Determination limit of this method was 0.5 pg/shot for T and 1 pg/shot for DHT. Concentration of T and DHT were expressed in pg/mg. T and DHT levels in tissue and blood were compared with Gleason score, clinical stage, and percentage of positive biopsy cores (% positive cores) by multivariate analyses. RESULTS Median value of PSA and prostate volume measured by ultrasound were 11.5 ng/mL and 27.7 cc, respectively. Median values of T and DHT in blood were 3551.0 pg/mL and 330.5 pg/mL, respectively. There was a strong correlation between serum T and DHT. Median values of T and DHT in tissue were 0.566 pg/mg and 7.062 pg/mg, respectively. In multivariate analysis, serum PSA and tissue T levels were significantly associated with poor prognosis factors in men with prostate cancer. High testosterone levels in prostate tissue were related to high Gleason score (p=0.041), advanced clinical stage (p=0.002), and high proportion of % positive cores (p=0.001). CONCLUSIONS Testosterone and dihydrotestosterone concentrations in blood or prostate tissue of needle biopsy were simultaneously examined by newly developed ultra sensitive quantifying method, LC-MS/MS. We confirmed that high testosterone levels in prostate tissue were related to high Gleason score, advanced clinical stage, and high proportion of % positive cores. These results suggest that testosterone level of needle biopsy specimens may be useful as a predictive factor in prostate cancer patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e872 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhide Miyoshi Yokohama, Japan More articles by this author Susumu Umemoto Yokohama, Japan More articles by this author Uemura Hiroji Yokohama, Japan More articles by this author Seijiro Honma Kawasaki, Japan More articles by this author Yasuhiro Shibata Maebashi, Japan More articles by this author Yohinobu Kubota Yokohama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of isoflavones on testicular weight and testosterone secretion in ISA Brown roosters

Abstract Isoflavones are phytoestrogens which have estrogen-like activity in animals and humans. Because of this characteristic influence, the aim of this investigation was to examine the effect of genistein and daidzein on testicular weight and testosterone secretion in ISA Brown roosters. Genistein and daidzein as non-steroid phytoestrogens were added in large amounts to the feed of roosters. Soy isoflavones were added to rooster diets in amounts of 0, 300, 600, 1200 and 1800 mg/kg of feed. At the end of the 37th week no significant differences were found between the groups in testicular weight (P>0.05) and testosterone secretion (P>0.05) measured in the blood of birds. Blood testosterone concentration was significantly higher in younger (20-week-old) roosters than in 37-weekold roosters (P<0.01). Genistein and daidzein present in the feed did not influence the weight of testes and no significant differences were found. Further studies are required to investigate the effect of isoflavones on other androgenic characteristics.

Goodbye International Journal of Andrology, welcome Andrology!

Goodbye <i>International Journal of Andrology</i>, welcome <i>Andrology</i>!

The association between perinatal testosterone concentration and early vocabulary development: A prospective cohort study

Prenatal exposure to testosterone is known to affect fetal brain maturation and later neurocognitive function. However, research on the effects of prenatal testosterone exposure has been limited by indirect measures of testosterone and small unrepresentative samples. This study investigated whether bioavailable testosterone (BioT) concentrations in umbilical cord blood are associated with expressive vocabulary development, in a large birth cohort. Cord blood samples were taken immediately after delivery and expressive vocabulary was measured at two years of age using the language development survey (LDS). BioT concentration significantly predicted vocabulary size in males (n=197), such that higher concentrations were associated with lower LDS scores, indicating smaller vocabulary. This relationship between BioT concentrations and vocabulary at aged 2 years was not observed in girls (n=176). Higher circulating prenatal testosterone concentrations at birth may be associated with reduced vocabulary in early childhood among boys.

Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study.

BackgroundIncreased prenatal testosterone exposure has been hypothesized as a mechanism underlying autism spectrum disorders (ASD). However, no studies have prospectively measured prenatal testosterone exposure and ASD. The current study sought to determine whether testosterone concentrations in umbilical cord blood are associated with a clinical diagnosis of ASD in a small number of children and with autistic-like traits in the general population.MethodsUmbilical cord blood was collected from 707 children. Samples were analyzed for total (TT) and bioavailable (BioT) testosterone concentrations. Parent report indicated that five individuals had a clinical diagnosis of ASD. Those participants without a diagnosis were approached in early adulthood to complete the Autism-Spectrum Quotient (AQ), a self-report measure of autistic-like traits, with 184 males (M = 20.10 years; SD= 0.65 years) and 190 females (M = 19.92 years; SD=0.68 years) providing data.ResultsThe BioT and TT concentrations of the five children diagnosed with ASD were within one standard-deviation of the sex-specific means. Spearman’s rank-order coefficients revealed no significant correlations between TT levels and scores on any AQ scale among males (rho range: -.01 to .06) or females (rho value range: -.07 to .01). There was also no significant association between BioT or TT concentrations and AQ scores among males (rho value range: -.07 to .08) or females (rho value range: -.06 to .12). Males were more likely than females to have ‘high’ scores (upper decile) on the AQ scale relating pattern and detail processing. However, the likelihood of a high score on this scale was unrelated to BioT and TT concentrations in both males and females.ConclusionsThese findings indicate that testosterone concentrations from umbilical cord blood are unrelated to autistic-like traits in the general population. However, the findings do not exclude an association between testosterone exposure in early intrauterine life and ASD.

Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo‐controlled trial

High doses of short-term testosterone have been shown to acutely worsen sleep-disordered breathing in men with obstructive sleep apnoea (OSA). The effects of lower, near-conventional doses of testosterone in obese men with OSA may differ over the longer term but have not been systematically studied. We assessed sleep and breathing effects of near-conventional testosterone treatment as an adjunct to weight loss in obese men with severe OSA. An 18-week randomized, double-blind, placebo-controlled, parallel group trial in 67 men. All subjects were placed on a hypocaloric diet and then received intramuscular injections of 1000 mg testosterone undecanoate or placebo at 0, 6 and 12 weeks. Sleep and breathing were measured by nocturnal polysomnography at 0, 7 and 18 weeks. Testosterone, compared to placebo, worsened the oxygen desaturation index (ODI) by 10·3 events/h (95%CI, 0·8-19·8 events/h; P = 0·03) and nocturnal hypoxaemia (sleep time with oxygen saturation <90%, SpO(2) T90%) by 6·1% (95%CI, 1·5-10·6; P = 0·01) at 7 weeks. Testosterone therapy did not alter ODI (4·5, -5·4 to 14·4 events/h; P = 0·36) or SpO(2) T90% at 18 weeks (2·9, -1·9-7·7%; P = 0·23) compared to placebo. The testosterone treatment effects on ODI and SpO(2) T90% were not influenced by baseline testosterone concentrations (testosterone by treatment interactions, all P > 0·35). Blood testosterone concentrations did not correlate with ODI or SpO(2) T90% (all P > 0·19). Testosterone therapy in obese men with severe OSA mildly worsens sleep-disordered breathing in a time-limited manner, irrespective of initial testosterone concentrations. This time-dependency was not related to testosterone concentrations. www.anzctr.org.au Identifier: ACTRN1260-6000404527.

Efficacy of treatment of vulva cancer patients and analysis of their hormonal status.

e21127 Background: hormonodependency of vulva is wellknown. This broughtusto study hormonal status of vulva cancer patients depending on treatment efficacy Methods: we present comparative analysis of hormonal status of vulva cancer patients in two groups: group 1 (50 patients) without relapse of the disease in 5-year period, and group 2 (35 patients) with relapse developed within the first year. Blood concentrations of testosterone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone were determined in all patients under study by means of radiometric methods. Estrone, estradiol, estriol with subsequent calculation of their sum were determined in daily urine by Brown method. Results: In the presence of effect (group 1) initial total amount of estrogens was twice as large than in its absence. In group 1 estradiol concentration exceeded the corresponding parameter of group 2 by three times(7.6±0.6 &amp; 1,4±0.3,p&lt;0.001). The amount of secreting estriol at positive result was almost twice higher than in cases of absence of the effect(10.02±1.7 &amp; 4.6±0.49, p&lt;0.001). The groups differed by secretion levels of follicle-stimulating and luteinizing hormones. Blood concentration of these hormones was lower in negative results that in positive. Distinct differences were also observed in progesterone and prolactin levels. In the group with positive result of treatment progesterone concentration was much higher than in the group without treatment effect. On the contrary, prolactin concentration in group 1 was significantly less than in group 2. The highest degree of reliability of quantitative indices related to treatment efficacy was observed for progesterone. Positive result of corresponding treatment may be predicted at normal initial progesterone level, and negative result at its low level (3-4 times lower than the norm). Another parameter - blood concentration of prolactin - can be used almost with the same degree of reliability. Conclusions: results of the study allow to suggest an existence of interrelation between treatment efficacy of vulva cancer patients and functional activity of hypophysis-gonadal system. Some of its parameters may be used to predict results of complex treatment of vulva cancer patients.

The Effects of Supplemental Vitamin E on Reproductive Development of Prepubertal Karya Male Lambs

The objective of this study was to determine the effect of dietary vitamin E supplementation on testicular and behavioural development, and histological appearance of testes in Karya male lambs. Thirteen lambs weaned at 2.5 months of age were used in the experiment. Experiment was carried out over a period of 70 days and all lambs were fed ad libitum on concentrate and 100 g/day clover hay per lamb. In addition, the experimental group (n=6) received a supplement of 45 mg/day vitamin E (dl-α-tocopherol acetate) per lamb. Testicular measurements and blood testosterone concentrations were recorded every second week. Behavioural tests were carried out four times per animal at three days intervals during the last 12 days of the experiment. After slaughtering, testicular tissue samples of all animals were collected and evaluated for the histological appearances. Except for mount attempts (P<0.05), sexual behaviour and testicular growth characteristics of the lambs were similar. The mounting parameters, testosterone concentrations and testes and epididymides weights were similar between the two groups. However, the mean of mounting weight was found lower (P<0.05) with Vitamin E lambs compared to control (28.78±3.48 vs. 33.98±3.64 kg, respectively). The area of seminiferous tubules was statistically different (P<0.001) between the two groups. However, there were no significant differences between the two groups for most of the reproductive characters. These findings suggest that supplementation of Vitamin E during early prepubertal age of Karya male lambs does not have considerable effects on the reproductive characteristics.

The effects of supplemental vitamin E on reproductive development of prepubertal Karya male lambs.

ABSTRACTThe objective of this study was to determine the effect of dietary vitamin E supplementation on testicular and behavioural development, and histological appearance of testes in Karya male lambs. Thirteen lambs weaned at 2.5 months of age were used in the experiment. Experiment was carried out over a period of 70 days and all lambs were fed ad libitum on concentrate and 100 g/day clover hay per lamb. In addition, the experimental group (n=6) received a supplement of 45 mg/day vitamin E (dl-α-tocopherol acetate) per lamb. Testicular measurements and blood testosterone concentrations were recorded every second week. Behavioural tests were carried out four times per animal at three days intervals during the last 12 days of the experiment. After slaughtering, testicular tissue samples of all animals were collected and evaluated for the histological appearances. Except for mount attempts (P<0.05), sexual behaviour and testicular growth characteristics of the lambs were similar. The mounting parameters, testosterone concentrations and testes and epididymides weights were similar between the two groups. However, the mean of mounting weight was found lower (P<0.05) with Vitamin E lambs compared to control (28.78±3.48 vs. 33.98±3.64 kg, respectively). The area of seminiferous tubules was statistically different (P<0.001) between the two groups. However, there were no significant differences between the two groups for most of the reproductive characters. These findings suggest that supplementation of Vitamin E during early prepubertal age of Karya male lambs does not have considerable effects on the reproductive characteristics.

Semen quality, testosterone, seminal plasma biochemical and antioxidant profiles of rabbit bucks fed diets supplemented with different concentrations of soybean lecithin

A total of 28 adult V-line rabbits were fed ad libitum a control diet or a diet supplemented with 0.5%, 1.0% and 1.5% soybean lecithin (SL) for 12 weeks. Bucks that received 0.5%, 1.0% or 1.5% dietary SL had a higher ejaculate volume, mass motility, sperm concentration, total sperm output and total motile sperm. Dietary SL reduced the percentage of dead sperm and increased the normal sperm, and this concurred with an increase in blood testosterone concentration. Blood and seminal plasma total lipid, acid phosphatase and seminal plasma alkaline phosphatase were significantly increased because of inclusion of SL. Interestingly, SL reduced blood and seminal plasma thiobarbituric acid-reactive substances while increasing blood and seminal plasma glutathione content, glutathione S-transferase, glutathione peroxidase and superoxide dismutase activity. Conception rate and litter size at birth and weaning were also significantly improved. Practically, it could be suggested that SL is a suitable supplement for improving semen quality, antioxidant status, reproductive traits and the economic efficiency of V-line rabbit bucks and 1% is an adequate concentration.

Clinical Significance of Blood Testosterone Concentration as a Cardiovascular Risk Factor: A Cardio-Ankle Vascular Index Study

要 旨：心血管疾患危険因子としての血中テストステロン濃度の臨床的意義を新たな動脈硬化指標であるcardio-ankle vascular index(CAVI)との関係から検討を行った。心血管疾患の既往がない中高年男性252名を対象とした。血中遊離テストステロン濃度とCAVIの間には有意な負の相関関係を認め，関連する因子で補正しても両指標の関係は有意であった。血中テストステロン濃度とCAVIの密接な関係が示された。

Testicular Fluid Content and Scrotal Surface Temperature Increase with Rams’ Sexual Activity

Contact with oestrual ewes induces an increase in LH and testosterone concentrations in rams. LH provokes an increase in testicular capillary permeability in rodents and an increase in testicular fluid in rams. Therefore, the objectives of the present experiment were to determine whether contact with oestrual ewes, including courtship and mating, induces an increase in testicular fluid content and scrotal temperature in rams. During the breeding season, after 2 weeks isolated from females, a total of 18 tests were performed using one ram with one ewe. The rams were allowed to court and mate the ewes during 20 min. Testosterone blood concentrations were measured by RIA from blood samples taken before and immediately after each test. Rectal, scrotal surface and anal skin temperatures were measured before the test, at the end, and 30 min later. At the same moments, ultrasonographic examinations of the testes were performed. Testosterone concentrations increased after the tests (p = 0.016), and ultrasound images were darker at the end of the tests and 30 min later (p < 0.0001). Rectal, anal skin and scrotal temperatures increased at the end of the test, but decreased 30 min later to initials values. The stimulus of oestrual ewes determined an increase in testosterone secretion, which was associated with an increase in testicular fluid content. Fluid content remained increased at least for 30 min after the end of the ram-ewe contact. Contact with oestrual ewes triggered an increase in testicular fluid that remained higher after the end of the test.

Age-related testosterone decline in a Brazilian cohort of healthy military men

Androgen decline in the aging man has become a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be accompanied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil. To determine the pattern of blood testosterone concentrations decline with age in a cohort of Brazilian healthy military men. We retrospectively reviewed data on serum testosterone measurements of healthy individuals that had undergone a routine check-up at the Military Biology Institute. Blood samples were obtained early in the morning, and total testosterone concentration was determined using a commercial chemoluminescent immunoassay. Mean values were analyzed in five age groups: ≤ 40, 41 to 50, 51 to 60, 61 to 70, and > 70 years. Mean total testosterone levels. 1,623 subjects were included in the analysis; mean age was 57 years (24 to 87), and mean testosterone level was 575.5 ng/dL (25.0 to 1308.0 ng/dL). The evaluation of age-related changes in total testosterone levels revealed a progressive reduction in serum levels of this hormone with increasing age. Testosterone levels below 300 ng/dL were reported in 321 participants, a prevalence of nearly 20% in the study population. In agreement with other findings, a reduction of total testosterone levels with age was reported for healthy Brazilian men.

Effects of early vaccination with Improvac ® on the development and function of reproductive organs of male pigs

Gonadotropin-releasing hormone (GnRH) vaccine (Improvac ®) is effective at diminishing boar taint by interfering with testis function. Early pre-pubertal vaccination at 10 and 14 weeks-of-age could be desirable if sufficient and sustained effects could be achieved. Crossbred male pigs ( n = 24) were randomly assigned to three groups each with eight individuals: an unvaccinated control group, one group vaccinated with Improvac ® early at ages 10 and 14 weeks, and a third group vaccinated with Improvac at the standard ages of 16 and 20 weeks. The average age at slaughter was 25 weeks. At slaughter, reductions in testes weight and bulbourethral gland length of vaccinated pigs compared with controls were observed ( P < 0.001), accompanied by lowered testosterone concentrations in peripheral blood ( P < 0.001). The diameter of tubuli seminiferi was affected; being 18% smaller in standard and 38% smaller in early vaccinated males, compared with controls ( P < 0.01). Leydig cells in vaccinated pigs became pycnotic, and their number decreased in early vaccinated pigs. Spermatogenesis was disrupted, evidenced by spermatocyte loss among standard vaccinated pigs to severe spermatogenic arrest among early vaccinated pigs. This histological picture was reflected in the absence of epididymal spermatozoa in 5 of 8 early vaccinated pigs and a dramatic reduction in the remaining 3 early vaccinated pigs. Among standard vaccinated pigs, 5% of the spermatozoa were morphologically normal (>70% in controls, P < 0.01). Early vaccination caused a more severe disruption of testicular structure and function than standard vaccination, thus providing an alternative for immunocastration of male pigs.

Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression

Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders.

Effect of tapering period on plasma hormone concentrations, mood state, and performance of elite male cyclists

In this study, we investigated the effect of 1- and 3-week tapering periods on concentrations of plasma testosterone (T), cortisol (C), T/C ratio, mood state, and performance in elite male cyclists. After 8 weeks of progressive training, cyclists were randomly assigned to a control group (n=12) who continued performing intense training for a further 3 weeks, or a taper group (n=12) who continued with a 50% reduction in training volume. Blood testosterone and cortisol concentrations were assayed and the T/C ratio calculated from analysis obtained via standard ELISA. Mood state was determined using the Profile of Mood States (POMS) questionnaire. All data were collected immediately after a 40-km time-trial performed before, during, and after the 8-week training protocol and after the 1- and 3-week tapering/training periods. In the taper group, 40-km time-trial time decreased significantly (P<0.01) and equally for both the 1- and 3-week taper periods relative to the control group. There were significant elevations in T/C ratio (P<0.001) and reductions in cortisol concentrations and POMS scores in the taper group relative to the control groups at the end of both the 1- and 3-week tapering periods. Hence, taper periods are effective in improving performance and mood state and elevating the blood T/C ratio.

Abstract LB-421: Characterization of castrate resistant prostate cancer treated with abiraterone acetate and prednisone

Abstract Background: Recent observations implicate persistent androgen signaling in metastatic castrate-resistant prostate cancer (mCRPC) progression. Inhibition of CYP 17 lyase with abiraterone acetate (AA) prolongs survival of patients (pts.) with mCRPC progressing after docetaxel (de Bono et al ESMO 2010). Despite initial benefit to AA, most pts. develop disease progression. The purpose of this study is to better understand resistance by characterizing mCRPC in bone marrow of pts. on AA. Methods: From October 2007 to March 2010, we performed an open-label, study of 57 pts. with metastatic CRPC, who underwent transilial bone marrow biopsy at baseline, 8 weeks and progression. Pts. received AA, 1 g once daily, and prednisone, 5 mg twice daily. The objective was to evaluate androgen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate findings with clinical observations. Androgen receptor (AR) and CYP17 expression was assessed by immunohistochemistry, and testosterone concentration by electrospray tandem mass spectrometry. AR copy numbers ( Real-Time PCR) and TMPRSS2-ERG ( FISH) were assessed in available tissues. Findings: Median overall survival was 555 days (95% CI: 440-965+). Maximal PSA decline of ≥50% occurred in 28 (50%) of 56 pts., and ≥90% in 9 (16%). Homogeneous, intense nuclear AR expression in combination with ≥10% CYP17 tumor expression correlated with longer time to treatment discontinuation (&amp;gt;4 months) in 25 pts. with tumor-infiltrated bone marrow. Pretreatment CYP17 expression of ≥10% in the tumor correlated with increased bone marrow testosterone. Blood and bone marrow testosterone concentration declined to below picogram levels and remained suppressed at progression. AR copy number increased over time in pts. with benefit from treatment as opposed to early progressors (≤ 4 months) where no difference was observed. Over expression of nuclear AR by immunohistochemistry was observed in (9/11) cancers from pts. benefiting, whereas 4/6 cancers from pts. with early progression a significant reduction in nuclear AR was seen. CYP 17 expression was lost in repeat biopsy performed at progression in 6/11 cancers available for analysis from pts. with prolonged response. Interpretation: The pretreatment expression profile observed is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that AA achieves sustained suppression of testosterone in blood and bone marrow to below picogram levels suggesting that progression is testosterone independent. Increased expression of AR in the context of sustained depletion of bone marrow testosterone by AA favors the hypothesis that "native ligand independent AR signaling" is implicated in abiraterone resistance. Our observations provide rationale for a combinatorial androgen signaling inhibition strategy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-421. doi:10.1158/1538-7445.AM2011-LB-421