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Steroid Levels (steroid + level)
Kinds of Steroid Levels Selected AbstractsSex Steroid Level, Androgen Receptor Polymorphism, and Depressive Symptoms in Healthy Elderly MenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2005Guy G. T'Sjoen MD Objectives: To determine the prevalence of depression in a cohort of elderly men as assessed using a 30-item Geriatric Depression Scale (GDS) score and to describe the association between this score and sex steroids, androgen receptor (AR) polymorphism, and general health status. Design: Observational study on the relationship between sex steroid status and health-related parameters. Setting: Community-based. Participants: Ambulatory men (n=236 in 1997, n=192 in 2000) aged 70 and older at inclusion in 1996, interviewed in 1997 and 2000. Measurements: Serum levels of testosterone, estradiol, sex hormone binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), cortisol, and the AR gene cytosine, adenine, guanine (CAG)-repeat length polymorphism were determined. Free testosterone and free estradiol were calculated. Questionnaires included GDS, 36-item Short Form, and Rapid Disability Rating Scale,2. Results: Median age was 75.3 years (interquartile range=73.5,78.5). A GDS score of 11 or greater was found in 30 (12.7%) men. Age and GDS score were significantly interrelated (P<.01), as were all health-assessment scores. GDS scores were not related to (free) testosterone or AR polymorphism in 1997 or 2000. In 1997 only (n=236), higher GDS scores were related to higher estradiol, free estradiol, and DHEAS levels. Conclusion: The data did not support a role for testosterone in depression in elderly community-based men as assessed using the GDS. [source] Naltrexone Selectively Elevates GABAergic Neuroactive Steroid Levels in Heavy Drinkers With the ASP40 Allele of the OPRM1 Gene: A Pilot InvestigationALCOHOLISM, Issue 8 2010Lara A. Ray Background:, Preclinical studies have implicated GABAergic neurosteroids in behavioral responses to alcohol. Naltrexone is thought to blunt the reinforcing effects of alcohol, and a few studies have found that the effects of naltrexone are moderated by the Asn40Asp polymorphisms of the OPRM1 gene. The present study seeks to integrate these lines of research by testing (i) the moderating role of the functional Asn40Asp polymorphism of the OPRM1 gene on naltrexone-induced alternations in GABAergic neurosteroid levels, namely (3,,5,)-3-hydroxypregnan-20-one (allopregnanolone, ALLO); and (ii) the combined effects of naltrexone or genotype with alcohol administration on neurosteroid levels in a sample of at-risk drinkers. Methods:, Participants were 32 (9 females) nontreatment-seeking heavy drinkers who completed a placebo-controlled laboratory study of naltrexone (50 mg/d for 3 days) and provided complete sets of serum samples for ALLO assays before and after alcohol administration under both naltrexone and placebo conditions. Results:, Naltrexone treatment raised ALLO levels among carriers of the Asp40 allele, but not homozygotes for the Asn40 allele. The Asn40Asp polymorphism did not moderate effects of naltrexone on cortisol levels. Ethanol infusion modestly reduced ALLO levels in all subjects, independent of genotype or naltrexone exposure. Conclusions:, Naltrexone increased ALLO levels among individuals with the Asn40Asp allele suggesting a potential neurosteroid contribution to the neuropharmacological effects of naltrexone among Asp40 carriers. [source] Strain differences in ,1 receptor-mediated behaviours are related to neurosteroid levelsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Vân-Ly Phan Abstract The sigma1 (,1) receptor exerts a potent neuromodulatory role in the brain with relevant consequences in memory processes, response to stress, depression and pharmacodependence. Its precise endogenous ligand is not yet identified but the ,1 receptor appears to be one target for the nongenomic rapid effects of neuroactive steroids in the brain. The aim of the present study was to establish whether differences in ,1 receptor-mediated behaviours could be observed among mouse strains, in relation with differences in either ,1 receptor expression or steroid levels. The ,1 -receptor immunohistochemical distribution appeared similar between Swiss and C57BL/6 strains in all the brain structures examined. The levels of in vivo[3H](+)-SKF-10 047 binding to ,1 receptors were lower in Swiss than in C57BL/6. Adrenalectomy/castration significantly increased [3H](+)-SKF-10 047 binding only in Swiss. The behavioural efficacy of the selective ,1 agonists igmesine and PRE-084 , reversion of the scopolamine-induced amnesia in the passive avoidance test; diminution of the immobility duration in the forced swimming test , were significantly higher in C57BL/6 than in Swiss. Steroid levels were measured in the brain in basal conditions and after stress. C57BL/6 mice presented in both conditions, the lowest progesterone levels, this steroid acting as an endogenous ,1 antagonist. Collectively, the results suggested that strain differences in neuroactive steroid and particularly, progesterone, biosynthesis and sensitivity may contribute to the differential behavioural efficacy of ,1 -receptor ligands. Noteworthy, these observations are coherent with strain differences observed in the intensity of cocaine-induced reward properties, known to critically involve the ,1 receptor. [source] Seasonal plasticity of brain aromatase mRNA expression in glia: Divergence across sex and vocal phenotypesDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2005Paul M. Forlano Abstract Although teleost fishes have the highest levels of brain aromatase (estrogen synthase) compared to other vertebrates, little is known of its regulation and function in specific brain areas. Previously, we characterized the distribution of aromatase in the brain of midshipman fish, a model system for identifying the neural and endocrine basis of vocal-acoustic communication and alternative male reproductive tactics. Here, we quantified seasonal changes in brain aromatase mRNA expression in the inter- and intrasexually dimorphic sonic motor nucleus (SMN) and in the preoptic area (POA) in males and females in relation to seasonal changes in circulating steroid hormone levels and reproductive behaviors. Aromatase mRNA expression was compared within each sex throughout non-reproductive, pre-nesting, and nesting periods as well as between sexes within each season. Intrasexual (male) differences were also compared within the nesting period. Females had higher mRNA levels in the pre-nesting period when their steroid levels peaked, while acoustically courting (type I) males had highest expression during the nesting period when their steroid levels peaked. Females had significantly higher levels of expression than type I males in all brain areas, but only during the pre-nesting period. During the nesting period, non-courting type II males had significantly higher levels of aromatase mRNA in the SMN but equivalent levels in the POA compared to type I males and females. These results demonstrate seasonal and sex differences in brain aromatase mRNA expression in a teleost fish and suggest a role for aromatase in the expression of vocal-acoustic and alternative male reproductive phenotypes. © 2005 Wiley Periodicals, Inc. J. Neurobiol, 2005 [source] Stress, the hippocampus, and epilepsyEPILEPSIA, Issue 4 2009Marian Joëls Summary Stress is among the most frequently self-reported precipitants of seizures in patients with epilepsy. This review considers how important stress mediators like corticotropin-releasing hormone, corticosteroids, and neurosteroids could contribute to this phenomenon. Cellular effects of stress mediators in the rodent hippocampus are highlighted. Overall, corticosterone,with other stress hormones,rapidly enhances CA1/CA3 hippocampal activity shortly after stress. At the same time, corticosterone starts gene-mediated events, which enhance calcium influx several hours later. This later effect serves to normalize activity but also imposes a risk for neuronal injury if and when neurons are concurrently strongly depolarized, for example, during epileptic activity. In the dentate gyrus, stress-induced elevations in corticosteroid level are less effective in changing membrane properties such as calcium influx; here, enhanced inhibitory tone mediated through neurosteroid effects on ,-aminobutyric acid (GABA) receptors might dominate. Under conditions of repetitive stress (e.g., caused from experiencing repetitive and unpredictable seizures) and/or early life stress, hormonal influences on the inhibitory tone, however, are diminished; instead, enhanced calcium influx and increased excitation become more important. In agreement, perinatal stress and elevated steroid levels accelerate epileptogenesis and lower seizure threshold in various animal models for epilepsy. It will be interesting to examine how curtailing the effects of stress in adults, for example, by brief treatment with antiglucocorticoids, may be beneficial to the treatment of epilepsy. [source] Strain differences in ,1 receptor-mediated behaviours are related to neurosteroid levelsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Vân-Ly Phan Abstract The sigma1 (,1) receptor exerts a potent neuromodulatory role in the brain with relevant consequences in memory processes, response to stress, depression and pharmacodependence. Its precise endogenous ligand is not yet identified but the ,1 receptor appears to be one target for the nongenomic rapid effects of neuroactive steroids in the brain. The aim of the present study was to establish whether differences in ,1 receptor-mediated behaviours could be observed among mouse strains, in relation with differences in either ,1 receptor expression or steroid levels. The ,1 -receptor immunohistochemical distribution appeared similar between Swiss and C57BL/6 strains in all the brain structures examined. The levels of in vivo[3H](+)-SKF-10 047 binding to ,1 receptors were lower in Swiss than in C57BL/6. Adrenalectomy/castration significantly increased [3H](+)-SKF-10 047 binding only in Swiss. The behavioural efficacy of the selective ,1 agonists igmesine and PRE-084 , reversion of the scopolamine-induced amnesia in the passive avoidance test; diminution of the immobility duration in the forced swimming test , were significantly higher in C57BL/6 than in Swiss. Steroid levels were measured in the brain in basal conditions and after stress. C57BL/6 mice presented in both conditions, the lowest progesterone levels, this steroid acting as an endogenous ,1 antagonist. Collectively, the results suggested that strain differences in neuroactive steroid and particularly, progesterone, biosynthesis and sensitivity may contribute to the differential behavioural efficacy of ,1 -receptor ligands. Noteworthy, these observations are coherent with strain differences observed in the intensity of cocaine-induced reward properties, known to critically involve the ,1 receptor. [source] Histological assessment of the testes coupled with determinations of sex steroid levels in Acipenser gueldenstaedtii males responding negatively to pituitary treatmentJOURNAL OF APPLIED ICHTHYOLOGY, Issue 2006Evgenii N. Artyukhin No abstract is available for this article. [source] Cloning of FSH-,, LH-, and glycoprotein hormone , subunits in pejerrey Odontesthes bonariensis (Valenciennes): expression profile and relationship with GnRH expression and plasma sex steroid levels in male fishJOURNAL OF FISH BIOLOGY, Issue 6 2007L. A. Miranda Three cDNAs encoding pejerrey Odontesthes bonariensis follicle stimulating hormone-, (FSH-,), luteinizing hormone-, (LH-,) and glycoprotein-, (GPH-,) subunits were cloned and characterized. Gene expression of these subunits was analysed by real-time polymerase chain reaction (PCR) and compared with the brain gene expression of endogenous gonadotropin-releasing hormones (GnRHs): Pacific salmon GnRH (GnRH-III), pejerrey GnRH (GnRH-I) and chicken GnRH-II (GnRH-II) and plasma sex steroid levels in adult males. The nucleotide sequences of the FSH-,, LH-, and GPH-, subunits are 466, 558 and 677 base pairs long, encoding for mature peptides of 102, 118 and 98 amino acids respectively. Maturing males had high expression of FSH-, and GPH-, subunits, and intermediate levels of LH-, when compared with running ripe and spent stages. These animals had the lowest plasma testosterone (T) and 11-ketosterone (11-KT) values as well as low expression of sGnRH, cGnRH-II and pjGnRH. Running ripe males had the lowest expression of FSH-, and the highest expression of LH-, and GPH-, subunits, and of the three GnRH genes. At this stage, the highest values of T and 11-KT were observed. Spent males showed low expression of the three gonadotropin (GtH) subunits, sGnRH, pjGnRH and low levels of T. At this stage, 11-KT levels and cGnRH-II expression showed a tendency to decrease but the values were not statistically significant (P < 0·05) to running ripe stage. The present results would suggest that T and 11-KT modulate the expression of the FSH subunits. The expression of the anterior brain GnRH variants, sGnRH and pjGnRH is correlated with LH-, expression and reinforce the importance of the forebrain GnRH variants on the regulation of pituitary function. [source] Rapid bioconcentration of steroids in the plasma of three-spined stickleback Gasterosteus aculeatus exposed to waterborne testosterone and 17,-oestradiolJOURNAL OF FISH BIOLOGY, Issue 3 2007R. J. Maunder The relationship over time between the concentrations of two steroids, singly and in combination, in a static exposure system and in the blood of three-spined stickleback Gasterosteus aculeatus, held within the exposure system was investigated. Groups of three-spined stickleback were exposed (nominally) to either 1000 ng l,1 17,-oestradiol (E2), testosterone (T) or E2 and T in combination at the same concentrations for 6 days. Both water and fish were sampled at intervals and steroid concentrations in both compartments were determined. The plasma steroid time profile revealed a rapid bioconcentration within the first 6 h of exposure. The plasma steroid levels attained at this time point (20,90 ng ml,1) were up to 50-fold (E2) and 200-fold (T) greater than the actual levels of steroid measured in the exposure water, while levels in the blood of control fish did not exceed 4 ng ml,1. The substantial elevation of plasma steroid levels relative to the concentrations of steroid to which the fish were exposed in the ambient water gives scope for delivery of the steroids to target endocrine tissues at levels far in excess of what might be predicted on the basis of passive branchial uptake alone. These results are discussed in relation to endocrine disruption, and in particular the occurrence of effects in fish exposed to levels of endocrine active substances that are seemingly physiologically irrelevant. [source] Reproductive biology of female big-bellied seahorsesJOURNAL OF FISH BIOLOGY, Issue 3 2004C. W. Poortenaar In this study, ovarian morphology, reproductive condition and sex steroid levels were investigated in the big-bellied seahorse Hippocampus abdominalis, collected by snorkel and SCUBA diving in Wellington Harbour, New Zealand. Within the ovary, oocytes were contained between an outer muscular wall and an inner layer of luminal epithelium. Two germinal ridges ran along the entire length of the ovary. In cross-section, oocytes were arranged in sequential order of development beginning at the germinal ridges and ending at the mature edge. Ovarian lamellae were absent. Vitellogenic and advanced cortical alveoli oocytes were elongated in shape, whereas maturing oocytes were distinctively pear-shaped. Mature oocytes were large (2·6 , 4·4 mm in length) and aligned with the animal pole towards the muscular wall. Reproductively mature females were found throughout the year indicating a protracted reproductive season. The gonado-somatic index was significantly different between all ovarian stages, but the hepato-somatic index was not. Females with previtellogenic ovaries had significantly higher plasma concentrations of testosterone than females with vitellogenic or maturing ovaries. There was no significant difference in plasma concentrations of testosterone between females with vitellogenic or maturing ovaries, or in plasma concentrations of 17,-oestradiol between females in all ovarian stages. This study contributes to the knowledge on the reproductive biology of female syngnathids. [source] Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye dropsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2007Thorsteinn Loftsson Delivery of steroids to the retina is currently undertaken with invasive injections into the vitreous cavity. This paper describes a non-invasive method to deliver steroids in therapeutic levels to the retina in rabbits. Dexamethasone was formulated as somewhat water-soluble dexamethasone/,-cyclodextrin (,CD) microparticles in a low-viscosity aqueous eye drop suspension. The mean (± standard deviation) diameter of the particles was 20.4 ± 10.3 ,m, with no particles larger than 60 ,m. The aqueous suspension formulation was tested in rabbits and compared with an aqueous dexamethasone eye drop solution containing randomly methylated ,-cyclodextrin (RM,CD). The dexamethasone concentration was identical in both formulations (15 mg mL,1). The drug was administered to the left eye but determined in both eyes. The amount reaching different eye tissues via the topical route was determined by subtracting the amount found in the right eye from the amount found in the left eye. Two hours after single application of the dexamethasone/,CD eye drops to rabbits the mean (± s.d.) concentration in vitreous was 29 ± 16 ng g,1, 86% of which reached vitreous via the topical route and in retina the concentration was 57 ± 22 ng g,1 (49% via topical route). For the RM,CD the values were 22.6 ± 9 and 66 ± 49 ng g,1 (73 and 14% via topical route), respectively. These steroid levels are comparable with the dexamethasone concentration achieved 1 month after intravitreal injection. The aqueous dexamethasone/,CD eye drop formulation was chemically stable during 7 months storage and well tolerated with no visible short-term side effects. [source] Altered expression of cytokines and sex steroid receptors in the reproductive tract of cysticercotic male micePARASITE IMMUNOLOGY, Issue 2 2010M. RODRÍGUEZ-DORANTES Summary Infection with Taenia crassiceps cysticerci in male mice produces an increase in serum oestradiol levels, whereas serum testosterone is abolished. Concomitantly, complete atrophy of the reproductive tract of infected male mice is observed. The present study was undertaken to determine the expression pattern of cytokines involved in steroidogenesis and sex steroid receptors in the reproductive tissues of normal and infected male mice, and relating this expression pattern to whole parasite counts, serum sex steroid levels and pathology of the reproductive tract in infected male mice. The expression of IL-4, IFN-, and TNF-, in testes and seminal vesicles was markedly increased in infected mice; however, IL-10 and IL-1, expression was importantly decreased in the same organs. IL-2 expression in reproductive tissues was not affected by infection. The infection markedly induced the expression of androgen receptor, in both reproductive organs tested, while subtypes of oestrogen receptors were decreased in both tissues. [source] Does second-to-fourth digit length ratio (2D:4D) predict age at menarche in women?AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Samuli Helle Prenatal steroid levels, estimated as the ratio of second-to-fourth digit length (2D:4D), have been related to reproductive success in women, but direct associations between 2D:4D and physiological measures of fertility remain rare. A recent study reported that lower, masculinized right hand 2D:4D was correlated with delayed age at menarche in women. We addressed this question by investigating whether 2D:4D was associated with recalled age at menarche in 282 post-reproductive Finnish women, using Cox regression model that controlled for a woman's sibling composition, urban or rural residence and temporal trend in menarcheal age. We found no evidence that neither the 2D:4D of the right nor the left hand were related to a woman's age at menarche among these Finnish women. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] The impact of developmental conditions on adult salivary estradiol levels: Why this differs from progesterone?AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2008Alejandra Núñez-De La Mora Women living in energetically stressful conditions have significantly lower baseline salivary steroid levels compared to those in affluent environments. Developmental hypotheses suggest that interpopulation variation in ovarian function results from contrasting environments experienced during growth. We use a migrant study of Bangladeshi women to test this hypothesis. We compared middle-class women (19,39 years) who migrated to London, UK, at different life-stages (pre and postmenarche), with Bangladeshi sedentees, second-generation British-Bangladeshis, and white British women living in similar London neighborhoods (total n = 227). We analyzed levels of salivary estradiol for one menstrual cycle, together with data on anthropometry, diet, lifestyle, and migration and reproductive histories. Results from multiple linear regression models, controlling for anthropometric and reproductive variables, show no significant differences in baseline estradiol levels between groups whether all cycles or just ovulatory cycles are analyzed. We also found no correlation between age at migration or time since migration on estradiol levels, nor between adult estradiol levels and age at menarche. Our results differ from previous reports of significantly lower salivary estradiol levels in populations living in more extreme ecological settings. They also contrast with our previous findings of significant intergroup differences in baseline levels of salivary progesterone. However, women who spent their childhood in Sylhet have a lower proportion of ovulatory cycles compared to women who developed in Britain. These group differences in ovulation frequency indicate more qualitative effects of contrasting developmental environments. We discuss possible explanations for differences in response between progesterone and estradiol, as well as broader implications of our findings. Am. J. Hum. Biol., 2008. © 2007 Wiley-Liss, Inc. [source] Validation of salivary cortisol and testosterone assays in chimpanzees by liquid chromatography-tandem mass spectrometryAMERICAN JOURNAL OF PRIMATOLOGY, Issue 8 2009Nobuyuki Kutsukake Abstract Owing to its high temporal sensitivity, saliva has distinct advantages for measuring steroids, compared with other noninvasive samples such as urine and feces. Here, we report the validity of assaying salivary cortisol (C) and testosterone (T) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in captive male chimpanzees, Pan troglodytes. For both the C and T concentrations, we found positive relationships between saliva and plasma. The concentrations of C and T in saliva showed clear patterns of diurnal fluctuation, whereas those in urine and feces did not. These results suggest that the salivary steroid concentrations can be regarded as good indicators of circulating steroid levels. We also developed and validated an efficient method for collecting saliva samples from cotton rope. Although rope includes inherent steroid-like compounds and may affect the accuracy of steroid measurements, our rope-washing procedures effectively removed intrinsic steroidal materials. There was a significant association between the C and T concentrations measured from saliva collected from rope licked by the chimpanzees and those measured from saliva collected directly from the mouth. Salivary T values estimated by LC/MS-MS were similar to those measured by radioimmunoassay. The results indicate the usefulness of saliva as a noninvasive steroid measure and that steroids in the saliva of chimpanzees can be accurately measured by LC-MS/MS. Am. J. Primatol. 71:696,706, 2009. © 2009 Wiley-Liss, Inc. [source] Assessing reproductive profiles in female brown mouse lemurs (Microcebus rufus) from Ranomafana National Park, southeast Madagascar, using fecal hormone analysisAMERICAN JOURNAL OF PRIMATOLOGY, Issue 6 2009Marina B. Blanco Abstract Studies on reproductive endocrinology in wild primate populations have greatly increased in the last decades owing to the development of noninvasive techniques that can be applied under field conditions. However, small-bodied nocturnal species are not well represented on the long list of primates surveyed in the wild, and reproductive inferences regarding these animals in their natural habitats have not benefited from direct observations of hormonal changes. We collected fecal samples from female brown mouse lemurs (Microcebus rufus) in a southeastern rainforest of Madagascar in order to determine whether or not fecally excreted steroid levels show a consistent pattern of change during the reproductive season and are a useful complement to reproductive observations in wild-trapped individuals. Initial data show variation in reproductive hormone levels before and after estrus and estimated day of parturition. Elevated levels of excreted estradiol (E2) were observed around the time of estrus, whereas high levels of fecal progesterone (P) were seen during later stages of pregnancy and around parturition. A more complete picture of reproductive profiles in female mouse lemurs, and how they may change over the life span, can be obtained if hormone analyses are used to supplement field observations. Am. J. Primatol. 71:439,446, 2009. © 2009 Wiley-Liss, Inc. [source] Influence of the mother's reproductive state on the hormonal status of daughters in marmosets (Callithrix kuhlii)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 1 2004Alyssa M. Puffer Abstract Behavioral and endocrine suppression of reproduction in subordinate females produces the high reproductive skew that characterizes callitrichid primate mating systems. Snowdon et al. [American Journal of Primatology 31:11,21, 1993] reported that the eldest daughters in tamarin families exhibit further endocrinological suppression immediately following the birth of siblings, and suggested that dominant females exert greater control over subordinate endocrinology during this energetically challenging phase of reproduction. We monitored the endocrine status of five Wied's black tufted-ear marmoset daughters before and after their mother delivered infants by measuring concentrations of urinary estradiol (E2), pregnanediol glucuronide (PdG), testosterone (T), and cortisol (CORT). Samples were collected from marmoset daughters 4 weeks prior to and 9 weeks following three consecutive sibling-litter births when the daughters were prepubertal (M=6.1 months of age), peripubertal (M=11.9 months), and postpubertal (M=17.6 months). The birth of infants was associated with reduced ovarian steroid excretion only in the prepubertal daughters. In contrast, ovarian steroid levels tended to increase in the postpubertal daughters. Urinary E2 and T levels in the postpubertal daughters were 73.8% and 37.6% higher, respectively, in the 3 weeks following the birth of infants, relative to prepartum levels. In addition, peak urinary PdG concentrations in peri- and postpubertal daughters were equivalent to luteal phase concentrations in nonpregnant, breeding adult females, and all of the peri- and postpubertal daughters showed clear ovulatory cycles. Cortisol excretion did not change in response to the reproductive status of the mother, nor did the concentrations change across age. Our data suggest that marmoset daughters of potential breeding age are not hormonally suppressed during the mother's peripartum period or her return to fertility. These findings provide an additional example of species diversity in the social regulation of reproduction in callitrichid primates. Am. J. Primatol. 64:29,37, 2004. © 2004 Wiley-Liss, Inc. [source] Arachidonic acid activation of intratumoral steroid synthesis during prostate cancer progression to castration resistanceTHE PROSTATE, Issue 3 2010Jennifer A. Locke Abstract BACKGROUND De novo androgen synthesis and subsequent androgen receptor (AR) activation has recently been shown to contribute to castration-resistant prostate cancer (CRPC) progression. Herein we provide evidence that fatty acids (FA) can trigger androgen synthesis within steroid starved prostate cancer (CaP) tumor cells. METHODS Tumoral FA and steroid levels were assessed by GC,MS and LC,MS, respectively. Profiles of genes and proteins involved in FA activation of steroidogenesis were assessed by fluorescence microscopy, immunohistochemistry, microarray expression profiling and Western blot analysis. RESULTS In human CaP tissues the levels of proteins responsible for FA activation of steroid synthesis were observed to be altered during progression to CRPC. Further investigating this mechanism in LNCaP cells, we demonstrate that specific FA, arachidonic acid, is synthesized in an androgen-dependent and AR-mediated manner. Arachidonic acid is known to induce steroidogenic acute regulatory protein (StAR) in steroidogenic cells. When bound to hormone sensitive lipase (HSL), StAR shuttles free cholesterol into the mitochondria for downstream conversion into androgens. We show that arachidonic acid induces androgen production in steroid starved LNCaP cells coincidently in the same conditions that HSL and StAR are predominantly localized in the mitochondria. Furthermore, their activities are verified by a functional increase in mitochondrial uptake of cholesterol in this steroid starved environment. CONCLUSIONS We propose that this characterized arachidonic acid induced steroidogenesis mechanism significantly contributes to the activation of AR in CRPC progression and therefore recommend that fatty acid pathways be targeted therapeutically in progressing CaP. Prostate 70: 239,251, 2010. © 2009 Wiley-Liss, Inc. [source] Declining and low fecal corticoids are associated with distress, not acclimation to stress, during the translocation of African rhinocerosANIMAL CONSERVATION, Issue 1 2010W. L. Linklater Abstract Concentrations of adrenal steroid metabolites in feces are routinely used to assess the welfare of animals that are the subject of conservation efforts. The assumption that low and declining corticoid concentrations indicate the absence of stress and acclimation, respectively, is often made without experimental support or wild-animal comparisons, although intrinsic control of adrenal steroids might occur even under ongoing stress and distress. We adopted the capture and 11-week captivity of 18 black (Diceros bicornis: 11 males, seven females) and 52 white (Ceratotherium simum: 22 males, 30 females) rhinoceros as an experimental test of the relationship between corticoid concentrations and stress (translocation) and measured for suppressed gonad function as an indicator of distress , the biological cost of cumulative stressors. Fecal samples collected from the rectum at capture and during captivity were stored frozen and their corticoid, and androgen (in males) or progestin (in females), concentrations determined by radioimmunoassay. Corticoid profiles followed the expected pattern of being two to five times pre-capture levels (ng g,1: black rhino: female 24.5±3.7, male 23.9±2.2; white rhino: female 16.3±1.6, male 12.3±2.4) for up to 17 days after capture and declined with time in captivity. Black rhinoceros and male white rhinoceros corticoids declined below pre-capture values and were associated with suppressed levels of androgens and progestins with increased time in captivity. Declining corticoids could not be interpreted as acclimation or the absence of stressors, without also measuring for distress in African rhinoceros. White rhinoceros female corticoid values remained elevated, although their gonad steroid levels were also suppressed. We discuss our findings for the management of rhinoceros in the wild and captivity. [source] | ||||||||||||||||