Dehydroepiandrosterone Concentrations Research Articles

Personality Types in Relation to the Periodontal Health Status and Salivary Dehydroepiandrosterone among Teachers in Baghdad City

Background: The individual differences in emotional and behavioral style can be examined through personality instruments. These differences may explain the health status of the individuals. The purpose of the present study was to assess the influence of Personality Types on gingival and periodontal health status among teachers in Baghdad city in relation to selected salivary hormone (Dehydroepiandrosterone). Materials and methods: Females teachers 534 of randomly selected schools were subjected to personality questionnaire using The Riso-Hudson Enneagram Type Indicator. Teachers were examined to estimate the periodontal status according to the Community Periodontal Index (CPI). A group of teachers were selected for salivary analysis of Dehydroepiandrosterone (DHEA). Results: Data analysis showed that the higher mean of scores was reported for the Helper personality Type among the sample. According to the maximum (CPI) code, significant difference was found in the mean values of Individualist Personality Type scores between the healthy periodontium (code 0) and calculus (code 2) of Community periodontal index. No significant correlation was found between salivary DHEA concentration (pg /ml) and the scores of the Nine Personality Types. No significant correlation was found between salivary DHEA concentration(pg/ml) and number of sextants for CPI codes. Conclusions: Personality Types could influence gingival and periodontal health status of the subjectsso that psychological interventions may be carried out to improve the oral hygiene condition of the population.

Overstocking dairy cows during the dry period affects dehydroepiandrosterone and cortisol secretion

Stressful situations trigger several changes such as the secretion of cortisol and dehydroepiandrosterone (DHEA) from the adrenal cortex, in response to ACTH. The aim of this study was to verify whether overstocking during the dry period (from 21±3 d to the expected calving until calving) affects DHEA and cortisol secretion and behavior in Holstein Friesian cows. Twenty-eight cows were randomly divided into 2 groups (14 animals each), balanced for the number of lactations, body condition score, and expected date of calving. Cows in the far-off phase of the dry period (from 60 to 21 d before the expected calving date) were housed together in a bedded pack. Then, animals from 21±3 d before the expected calving until calving were housed in pens with the same size but under different crowding conditions due to the introduction of heifers (interference animals) into the pen. The control condition (CTR) had 2 animals per pen with 12.0m2 each, whereas the overstocked condition (OS) had 3 interference animals in the same pen with 4.8m2 for each animal. On d −30±3, −21±3, −15±3, −10±3, and −5±3 before and 10, 20, and 30 after calving, blood samples were collected from each cow for the determination of plasma DHEA and cortisol concentrations by RIA. Rumination time (min/d), activity (steps/h), lying time (min/d), and lying bouts (bouts/d) were individually recorded daily. In both groups, DHEA increased before calving and the concentration declined rapidly after parturition. Overstocking significantly increased DHEA concentration compared with the CTR group at d −10 (1.79±0.09 vs. 1.24±0.14 pmol/mL), whereas an increase of cortisol was observed at d −15 (3.64±0.52 vs. 1.64±0.46ng/mL). The OS group showed significantly higher activity (steps/h) compared with the CTR group. Daily lying bouts tended to be higher for the OS group compared with CTR group in the first week of treatment. The overall results of this study documented that overstocking during the dry period was associated with a short-term changes in DHEA and cortisol but these hormonal modifications did not influence cow behavior.

Dioscorea esculenta-induced increase in muscle sex steroid hormones is associated with enhanced insulin sensitivity in a type 2 diabetes rat model.

The effects of chronic Dioscorea esculenta administration and exercise training on muscle sex steroid hormone levels and insulin resistance in type 2 diabetes rats was assessed. Twenty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were assigned randomly to the control, D. esculenta treatment, D. esculenta with 5α-reductase inhibitor treatment, or the exercise training groups (running at 25 m/min for 1 h, 5 d/wk; n = 10 each group). Eight weeks of D. esculenta treatment or exercise training significantly attenuated the increase in plasma insulin and fasting glucose levels. Plasma and muscle concentrations of dehydroepiandrosterone and 5α-dihydrotestosterone (DHT) and the expression of 5α-reductase increased significantly in the D. esculenta-treated and exercise training groups, and both treatments led to the upregulation of glucose transporter-4 translocation with concomitant increases in PKB and PKC-ζ/λ phosphorylation. Furthermore, the glucose metabolic clearance rate, which represents insulin sensitivity, increased significantly in both the D. esculenta-treated and exercise training groups. These effects were suppressed by administration of the DHT synthetic inhibitor. Together, these findings suggest that the D. esculenta-induced increase in muscle sex steroid hormone levels helps decrease insulin resistance in type 2 diabetes.-Sato, K., Fujita, S., Iemitsu, M. Dioscorea esculenta-induced increase in muscle sex steroid hormones is associated with enhanced insulin sensitivity in a type 2 diabetes rat model.

Postmenopausal cognitive changes and androgen levels in the context of apolipoprotein E polymorphism.

IntroductionThe focus of this study was to assess cognitive functions in relation to androgens and specifically testosterone and dehydroepiandrosterone in postmenopausal women as well as the correlation between cognitive functions and these two androgens according to polymorphism of the apolipoprotein E gene (APOE).Material and methodsA group of 402 women was recruited to the study (minimum 2 years after the last menstruation, follicle-stimulating hormone (FSH) more than 30 U/ml and no dementia signs on Montreal Cognitive Assessment). The computerized battery of the Central Nervous System Vital Signs test was used to diagnose cognitive functions. APOE genotyping was performed by multiplex polymerase chain reaction (PCR). Testosterone (TTE) and dehydroepiandrosterone (DHEA) in the blood serum were assessed for further statistical correlations analysis.ResultsIn the group of postmenopausal women, higher testosterone concentration was associated with lower scores for Neurocognition Index (NCI) (p = 0.028), memory (p = 0.008) and psychomotor speed (p < 0.001). Presence of at least one APOE ε4 allele potentiated testosterone’s negative influence on cognitive functions (p < 0.05). Woman with a high normal level of DHEA scored significantly better in verbal (p = 0.027) and visual memory (p < 0.001) than other participants. APOE polymorphism did not modify the relationship between DHEA concentration and scores for cognitive functions.ConclusionsHormonal balance variations after menopause may influence brain processes concerned with cognition, especially memory and psychomotor speed. The observed effects may be related to androgens’ influence on higher cortical functions in the changed hormonal dynamics of the postmenopausal period.

Correlation between dehydroepiandrosterone and occurrence of chronic urticaria

Chronic urticaria (CU) is a common skin disease with complex etiology and pathogenesis, and its cause is unclear in about 80% of patients. In clinic, there are many problems with CU, such as complicated condition, frequent recurrence, poor therapeutic effect of antihistamines, and so on, which seriously affect life quality of patients. In recent years, neuroendocrine-immune system dysfunction has got more and more attention, and has been suggested to play an important role in the pathogenesis of CU. Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) , which are secreted and regulated by the nervous system, participate in the process of neuroimmune regulation, and are regarded as potential factors regulating immune homeostasis. It has been reported that serum levels of DHEA and DHEA-S markedly decrease in patients with CU. It is unclear whether the decrease of DHEA and DHEA-S circulation concentrations is a primary cause or just a concomitant symptom of CU, and what role it plays in the development of CU. Key words: Dehydroepiandrosterone sulfate; Urticaria; Neuroendocrinology; Incidence; Severity of illness

Neuroendocrine factors distinguish juvenile psychopathy variants.

The characteristic pattern of emotional hypo-reactivity observed in primary psychopathy is not evident in secondary psychopathy, which is thought to originate from childhood adversity and co-occurring anxiety. The main aim of this study was to test whether salivary afternoon cortisol, Dehydroepiandrosterone (DHEA), and cortisol-to-DHEA concentrations, which at high levels indicate risk for chronic stress and poor mental health, distinguished secondary from primary variants of callous-unemotional (CU) traits-the affective component of psychopathy. This aim was achieved by first identifying psychopathy variants using latent profile analysis of CU, anxiety, and aggression scores among 232 incarcerated adolescent boys (M age = 16.75). Based on a subset with neuroendocrine data (n = 201), aggressive secondary CU variants had lower afternoon DHEA concentrations and higher cortisol-to-DHEA ratios and comorbid psychopathology compared with all other groups. In contrast, two primary CU variants (aggressive and non-aggressive types) emerged with profiles characterized by low to average psychopathology and high DHEA levels. Findings contribute to a growing literature base suggesting that biomarkers may distinguish youth on separable developmental pathways to psychopathy.

Abstract # 1855 Latent virus reactivation in astronauts during international space station

Latent virus reactivation and diurnal salivary cortisol and dehydroepiandrosterone (DHEA) were measured prospectively in 23 astronauts (18 male and 5 female) before, during, and after long duration (60–180 days) space missions on the International Space Station (ISS). Blood, urine, and saliva samples were collected during each of three phases (before, during, and after) spaceflight. Twenty age and sex matched healthy round based subjects were included in the study as a control group. Viral DNA was measured for Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). One astronaut did not shed targeted viruses in any samples collected during the three mission phases. Simultaneous shedding of all three viruses (EBV, VZV, and CMV) was observed in 8 astronauts. The viruses reactivated independently of each other. Reactivation of EBV, VZV, and CMV increased in frequency, duration, and amplitude (viral copy numbers) when compared to short duration (10–16 days) space shuttle missions. Herpes simplex (HSV 1 and 2) and human herpes virus 6 did not reactivate. Mean salivary cortisol increased significantly during flight as compared to before flight (p = 0.010). There was no difference between the after flight and before-flight (p = .048) levels of cortisol. DHEA concentrations did not change significantly for ISS crew members.

In vitro influence of light radiation on hair steroid concentrations

Hair cortisol concentrations (hairF) are considered to be relatively robust to various confounding influences. However, a potentially important covariate factor that has received little attention in this context is hair exposure to ultraviolet/sunlight radiation. We conducted a detailed experimental investigation to examine the effects of light exposure on hair cortisol. In study I, a hydrocortisone-containing solution was subjected to short-term artificial light irradiation for 1, 3, 5, 10, 15, or 30min to evaluate the stability of cortisol molecules due to radiant energy. In study II, hair samples (N=12) were subjected to single short-term artificial light irradiation for 0, 1, or 5h to examine light-induced effects in the hair matrix. In study III, hair samples (N=25) were subjected to long-term naturalistic sunlight radiation over a period of two months (during summer) with daily exposure times of 0, 1, 3, or 6h, respectively. Besides cortisol, studies II & III also examined concentrations of cortisone (hairE), dehydroepiandrosterone (hairDHEA) and progesterone (hairP) in hair, quantified using LC–MS/MS technology. Results across the three studies consistently revealed effects of light irradiation on hair steroid concentrations: Longer light exposure resulted in a decrease of dissolved hydrocortisone (study I) as well as of hairF and hairE (studies II and III). Conversely, hairDHEA and hairP increased with longer natural sunlight exposure times (study III), while this effect was not observed for short-term artificial light irradiation (study II). Combined, our findings imply sunlight exposure as a potential confound in hair steroid research. Given the experimental character of this investigation, the magnitude of this effect under real-life testing conditions is difficult to estimate. To support future investigation into this, we designed a ‘sunlight-exposure’ questionnaire to share with the research community. The assessment and statistical accounting for sunlight exposure-related effects in future hair steroid research (using this or a similar questionnaire) may help to reduce the potential influence of this unwanted error source and could thus lead to more valid and reliable results. In addition, our data strongly suggest that hair samples for steroid analyses need to be stored in a dark environment.

Antioxidant Protection of NADPH-Depleted Oligodendrocyte Precursor Cells Is Dependent on Supply of Reduced Glutathione.

The pentose phosphate pathway is the main source of NADPH, which by reducing oxidized glutathione, contributes to antioxidant defenses. Although oxidative stress plays a major role in white matter injury, significance of NADPH for oligodendrocyte survival has not been yet investigated. It is reported here that the NADPH antimetabolite 6-amino-NADP (6AN) was cytotoxic to cultured adult rat spinal cord oligodendrocyte precursor cells (OPCs) as well as OPC-derived oligodendrocytes. The 6AN-induced necrosis was preceded by increased production of superoxide, NADPH depletion, and lower supply of reduced glutathione. Moreover, survival of NADPH-depleted OPCs was improved by the antioxidant drug trolox. Such cells were also protected by physiological concentrations of the neurosteroid dehydroepiandrosterone (10−8 M). The protection by dehydroepiandrosterone was associated with restoration of reduced glutathione, but not NADPH, and was sensitive to inhibition of glutathione synthesis. A similar protective mechanism was engaged by the cAMP activator forskolin or the G protein-coupled estrogen receptor (GPER/GPR30) ligand G1. Finally, treatment with the glutathione precursor N-acetyl cysteine reduced cytotoxicity of 6AN. Taken together, NADPH is critical for survival of OPCs by supporting their antioxidant defenses. Consequently, injury-associated inhibition of the pentose phosphate pathway may be detrimental for the myelination or remyelination potential of the white matter. Conversely, steroid hormones and cAMP activators may promote survival of NADPH-deprived OPCs by increasing a NADPH-independent supply of reduced glutathione. Therefore, maintenance of glutathione homeostasis appears as a critical effector mechanism for OPC protection against NADPH depletion and preservation of the regenerative potential of the injured white matter.

The effects of a low-calorie diet or an isocaloric diet combined with metformin on sex hormones In obese women of child-bearing age.

The influence of weight loss treatment on sex hormones profile has been studied mainly in women with polycystic ovary syndrome (PCOS), but in obese premenopausal women without PCOS it still remains unclear. The aim of the study was to evaluate the effect of two approaches to obesity treatment on the serum level of sex hormones in obese women of child-bearing age without PCOS. 77 obese Caucasian women (aged 31.2 ±8.3 years) were randomized into two groups: 39 women received a low-calorie diet (LC) and 38 received an isocaloric diet plus metformin (IM), for 12 weeks. Anthropometric parameters, body composition and serum concentrations of estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and dehydroepiandrosterone (DHEA-S) sulfate were evaluated at baseline and after the study. Reductions in body weight, body mass index (BMI), waist and body fat content with an increase in lean body percent were significant and comparable between the LC and IM group after the trial. The concentrations of serum FSH, LH, E2, DHEA and T did not change in either group after treatment. A tendency towards an increase in the E2 concentration in both groups and a decrease in the T level in the LC group was observed. The correlations between a change in BMI, fat content, waist-hip ratio and a change in T were documented in the LC group. A 12-week low-calorie diet and an isocaloric diet combined with metformin produced comparable and significant weight loss with improvements in body composition. Both interventions did not significantly affect FSH, LH and DHEA sulfate serum concentrations, only a trend towards an E2 increase and a T decrease was observed, stronger in LC group. The significant correlations shown between the changes in anthropometric and body composition parameters and T serum levels in women treated with a low-calorie diet alone show the beneficial effect of a lifestyle intervention on the sex hormone in obese premenopausal women.

Hair cortisol concentration and glycated hemoglobin in African American adults

BackgroundAfrican Americans have higher diabetes prevalence compared to Whites. They also have elevated cortisol levels − indicating possible HPA axis dysregulation − which may raise blood glucose as part of the biological response to physiological and psychosocial stress. Little is known about chronic cortisol levels in African Americans, and even less about the role of chronically elevated cortisol in type 2 diabetes development in this racial group. PurposeWe used analysis of cortisol in hair to examine associations of long-term (∼3months) cortisol levels with glycated hemoglobin (HbA1c) in a group of African American adults. In exploratory analyses, we also studied the relationship of hair dehydroepiandrosterone (DHEA) with HbA1c. MethodParticipants were 61 community-dwelling African American adults (85% female; mean age 54.30 years). The first 3cm of scalp-near hair were analyzed for cortisol and DHEA concentration using enzyme-linked immunoassay analysis. Glycated hemoglobin was assessed, and regression analyses predicting HbA1c from hair cortisol and DHEA were performed in the full sample and in a subsample of participants (n=20) meeting the National Institute of Diabetes and Digestive Kidney Disease (NIDDK) criteria for type 2 diabetes (HbA1c≥6.5%). ResultsIn the full sample, HbA1c increased with hair cortisol level (β=0.22, p=0.04, f2=0.10), independent of age, sex, chronic health conditions, diabetes medication use, exercise, and depressive symptoms. In the subsample of participants with an HbA1c≥6.5%, hair cortisol was also positively related to HbA1c (β=0.45, p=0.04, f2=0.32), independent of diabetes medication use. Glycated hemoglobin was unrelated to hair DHEA in both the full sample and HbA1c≥6.5% subsample. ConclusionLong-term HPA axis dysregulation in the form of elevated hair cortisol is associated with elevated HbA1c in African American adults.

ИЗМЕНЕНИЕ ГОРМОНАЛЬНОГО СТАТУСА У ЖЕНЩИН С ГРИППОМ А(Н3N2) В ПЕРВОМ ТРИМЕСТРЕ БЕРЕМЕННОСТИ

The contents of β-subunit of chorionic gonadotropin (β-CG), estriol, progesterone, dehydroepiandrosterone (DEAS), placental lactogen and cortisol were studied in 164 women of child-bearing age at the 7-9th weeks of pregnancy. The first group (control) consisted of 30 women with physiologic course of pregnancy. The second group (comparison) had 32 patients with the threat of premature delivery of non-infectious etiology. The third group included 36 patients with influenza virus А(Н3N2) (anti-virus antibody titers were 1:4-1:16); the fourth group had 34 women with influenza virus А(Н3N2) (antibody titers were 1:8-1:32); in the fifth group there were 32 patients with influenza virus А(Н3N2) (antibody titers were 1:32-1:128) and the threat of premature delivery in the period of reconvalescence. The patients of the fifth group had the decrease of the level of β-CG till 40.5±2.0 mМЕ/ml, of estriol till 3.4±0.21 nmole/l, of progesterone till 35.1±3.13 nmole/l, of DEAS till 7.3±0.68 nmole/l, of placental lactogen till 12.1±1.0 nmole/l, as well as the increase of cortisol till 738.7±22.08 nmole/l in comparison with 73.0±2.0 mМЕ/ml (р&amp;#60;0.001), 5.9±0.33 nmole/l (р&amp;#60;0.001), 70.6±4.14 nmole/l (р&amp;#60;0.001); 7.3±0.68 nmole/l (р&amp;#60;0.001), 12.1±1.0 nmole/l (р&amp;#60;0.001) and 567.8±24.02 nmole/l (р&amp;#60;0.001) in the first group, respectively. The differences of hormonal status in the fifth and third group consisted of the drop of concentration of β-CG by 22.8% (р&amp;#60;0.001), of estriol by 26.1% (р&amp;#60;0.01), of progesterone by 32.1% (р&amp;#60;0.001) and placental lactogen by 32.4% (р&amp;#60;0.001). At the same time there were no significant changes in the concentration of DEAS and there were registered higher indicators of cortisol, i.e. the increase by 11.5% (р&amp;#60;0.05), which suggested the significance of the growth of antivirus antibody titers in the suppression of synthesis of hormones in ovaries and in syncytiotrophoblast as a result of direct and indirect negative influence of influenza infection.

Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress

Perturbations in an organism’s environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male’s CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on environmental, and particularly current social conditions.

Pilot study of adrenal steroid hormones in hair as an indicator of chronic mental and physical stress.

Currently, the quantitative analysis of moderators affecting the function of the hypothalamus-pituitary-adrenal (HPA)-axis in health and sickness is still unreliable. This is, in particular, due to physiological factors such as pulsatile ultradian and circadian glucocorticoid secretion as well as to methodological limitations of the current techniques for steroid hormone determination. Based on this background, the determination of long-term hair steroid concentrations is an important methodological improvement allowing for the quantitative analysis of chronic HPA axis-activation. In order to determine the relationship between chronic mental and physical stress and a chronic activation of the HPA axis, we performed a cross-sectional pilot-study with 40 healthy students and examined the relationships between physical activity, mental burden(s), subjective stress perceptions, depressiveness, anxiety, physical complaints, sense of coherence, resilience, and the long-term integrated steroid hormone levels in hair. The results showed that the concentrations of cortisol, cortisone, and dehydroepiandrosterone in hair were significantly correlated to mental (p = 0.034) and physical stress (p = 0.001) as well as to subjective stress perception (p = 0.006). We conclude that steroid concentrations in hair are decisive predictors for an increase in the long-term-HPA axis activity. Moreover, this biomarker is suitable for capturing the stresslevel after burdening events and physical activity.

Neferine increase in vitro anticancer effect of dehydroepiandrosterone on MCF-7 human breast cancer cells

This study was conducted to investigate the in vitro anticancer reinforcing effects of neferine (Nef) on dehydroepiandrosterone (DHEA) and the mechanism was also determined during the investigation. By the growth effects of Nef and DHEA on MCF-7 human breast cancer cells, 8 mg/mL Nef was a non-virulent concentration in MCF-7 cells, and this concentration was used for further experiment. In 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay, 30 mg/mL DHEA showed 49.4 % growth inhibitory effect in MCF-7 cells, whereas Nef (8 mg/mL) + DHEA (30 mg/mL) treatment had the higher effect at 67.8 %. The flow cytometry analysis results showed that 15 and 30 mg/mL DHEA-treated MCF-7 cells had 12.2 and 21.6 % apoptotic cells, respectively, Nef + DHEA could raise the apoptotic cells to 36.7 %. Reverse transcription-polymerase chain reaction assay shows remarkable results according to which DHEA could significantly increase caspase-3, caspase-8, caspase-9, Bax, p53, p21, E2F1, Fas, FasL mRNA expressions and decrease Bcl-2, Bcl-xL, HIAP-1, HIAP-2, survivin expressions as compared to the untreated control cancer cells. Moreover, these effects depend on the concentration of DHEA, and Nef which could further strengthen these effects. From these results, low concentration of Nef could not influence the growth of MCF-7 cells, but using its sensitization effect, Nef raised the in vitro effects of DHEA. Nef could be got easily. With these results we can accomplish that Nef + DHEA might be used as the new anticancer materials combination.

Production of 7α,15α-diOH-DHEA from dehydroepiandrosterone by Colletotrichum lini ST-1 through integrating glucose-feeding with multi-step substrate addition strategy.

Hydroxylation of dehydroepiandrosterone (DHEA) to 3β,7α,15α-trihydroxy-5-androstene-17-one (7α,15α-diOH-DHEA) by Colletotrichum lini ST-1 is an essential step in the synthesis of many steroidal drugs, while low DHEA concentration and 7α,15α-diOH-DHEA production are tough problems to be solved urgently in industry. In this study, the significant improvement of 7α,15α-diOH-DHEA yield in 5-L stirred fermenter with 15g/L DHEA was achieved. To maintain a sufficient quantity of glucose for the bioconversion, glucose of 15g/L was fed at 18h, the 7α,15α-diOH-DHEA yield and dry cell weight were increased by 17.7 and 30.9%, respectively. Moreover, multi-step DHEA addition strategy was established to diminish DHEA toxicity to C. lini, and the 7α,15α-diOH-DHEA yield raised to 53.0%. Further, a novel strategy integrating glucose-feeding with multi-step addition of DHEA was carried out and the product yield increased to 66.6%, which was the highest reported 7α,15α-diOH-DHEA production in 5-L stirred fermenter. Meanwhile, the conversion course was shortened to 44h. This strategy would provide a possible way in enhancing the 7α,15α-diOH-DHEA yield in pharmaceutical industry.

Endocrine and hematological responses of beef heifers divergently ranked for residual feed intake following a bovine corticotropin-releasing hormone challenge.

The objective of this study was to determine if beef heifers divergently ranked on phenotypic residual feed intake (RFI) differed in their physiological stress response to an exogenous bovine corticotropin-releasing hormone (bCRH) challenge. Yearling Limousin × Friesian heifers ( = 86) were ranked by RFI. The 15 highest (mean 0.66 kg DM/d; high RFI) and 15 lowest (mean -0.72 kg DM/d; low RFI) ranking animals were used for this study. During the study period, heifers (mean age 485 ± 13 d; mean BW 408 ± 31.4 kg) were housed in a slatted-floor facility. To facilitate intensive blood collection, heifers were fitted aseptically with indwelling jugular catheters. All heifers received dexamethasone (DEX; 20 µg/kg BW i.m.) 12 h before the bCRH challenge (d 0). Heparinized blood samples were collected at -60 and 0 min before administration of DEX, and 12 h after DEX administration. Following DEX administration, cortisol and dehydroepiandrosterone (DHEA) concentrations similarly decreased ( ≥ 0.22) between high and low RFI groups. The response of the HPA axis to a standardized dose of bCRH (0.3 μg/kg BW) was examined. On d 0, serial blood samples were collected at -20, 0, 20, 40, 60, 80, 100, 120, 150, 180, 210, 240, 270, 330, and 390 min relative to the time of bCRH administration (0 min) and were analyzed for plasma cortisol and DHEA concentrations. Blood hematology variables were also determined at -20, 0, 20, 80, 150, 270, 330, and 390 min relative to bCRH administration. Neither an RFI × sampling time interaction nor a direct effect of RFI were detected ( ≥ 0.36) for plasma cortisol, DHEA concentrations, or cortisol:DHEA ratio. An effect of sample time was observed for cortisol ( < 0.001), DHEA ( = 0.04), and cortisol:DHEA ( = 0.02), with cortisol concentration peaking at 60 min post-CRH administration. The maximum concentration and rate of change in cortisol and DHEA concentrations following bCRH administration were not different ( ≥ 0.20) between the high and low RFI phenotypes. Similarly, an effect of RFI was not evident ( ≥ 0.16) for any of the hematology variables examined including neutrophil, lymphocyte, and leukocytes counts; white and red blood cell numbers; and hemoglobin concentrations. Our results suggest that responsiveness of the HPA to stress, at least at the level of the anterior pituitary gland, is not a significant contributor to variation in RFI among growing beef heifers.

Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism.

Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone and cortisol. We assessed the utility of LC-MS/MS-based steroid profiling to stratify patients with primary aldosteronism. Fifteen adrenal steroids were measured by LC-MS/MS in peripheral and adrenal venous plasma from AVS studies for 216 patients with primary aldosteronism at 3 tertiary referral centers. Ninety patients were diagnosed with BAH and 126 with APAs on the basis of immunoassay-derived adrenal venous aldosterone lateralization ratios. Among 119 patients confirmed to have APAs at follow-up, LC-MS/MS-derived lateralization ratios of aldosterone normalized to cortisol, dehydroepiandrosterone, and androstenedione were all higher (P < 0.0001) than immunoassay-derived ratios. The hybrid steroids, 18-oxocortisol and 18-hydroxycortisol, also showed lateralized secretion in 76% and 35% of patients with APAs. Adrenal venous concentrations of glucocorticoids and androgens were bilaterally higher in patients with BAH than in those with APAs. Consequently, peripheral plasma concentrations of 18-oxocortisol were 8.5-fold higher, whereas concentrations of cortisol, corticosterone, and dehydroepiandrosterone were lower in patients with APAs than in those with BAH. Correct classification of 80% of cases of APAs vs BAH was thereby possible by use of a combination of steroids in peripheral plasma. LC-MS/MS-based steroid profiling during AVS achieves higher aldosterone lateralization ratios in patients with APAs than immunoassay. LC-MS/MS also enables multiple measures for discriminating unilateral from bilateral aldosterone excess, with potential use of peripheral plasma for subtype classification.

Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.