Dehydroepiandrosterone Concentrations Research Articles

The relationship between perinatal exposure to dioxins and serum steroid hormone levels in preschool-aged children at an e-waste region in China.

Perinatal exposure to dioxins affects steroid hormone synthesis. The purpose of the present study was to evaluate the associations between perinatal exposure to dioxins and serum steroid hormone levels in preschool-aged children from an e-waste recycling region in China. In the present study, we enrolled 50 pairs of mothers and infants from the Taizhou, Luqiao region in 2015. Of the 50 pairs of mothers and infants, 42 pairs participated in this study when the children were 4 years old. We measured breast milk dioxin concentrations using high-resolution gas chromatography/mass spectrometry. Additionally, we used liquid chromatography-tandem mass spectrometry to measure the concentrations of progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA) in serum samples from the 4-year-old children. We used multivariate linear regressions to assess the associations between dioxin congeners and steroid hormones. Results were reported as beta estimates and 95% confidence intervals by bootstrapping. We observed sex-related differences between breast milk dioxins and serum steroid hormone levels in 4-year-old children. An increase in breast milk dioxins was associated with a decrease in testosterone in serum samples from boys. Similarly, an increase in breast milk dioxins was associated with a decrease in progesterone levels in serum samples from girls. However, dioxins were not associated with changes in the levels of testosterone, DHEA, or A-dione in girls. Based on these results, we conclude that perinatal exposure to dioxins modifies steroidogenesis in preschool-aged children. However, the long-term impact of dioxins requires further large-scale studies to assess these effects in school-going children and adolescents.

Slow-, Tight-Binding Inhibition of CYP17A1 by Abiraterone Redefines Its Kinetic Selectivity and Dosing Regimen.

Substantial evidence underscores the clinical efficacy of inhibiting CYP17A1-mediated androgen biosynthesis by abiraterone for treatment of prostate oncology. Previous structural analysis and in vitro assays revealed inconsistencies surrounding the nature and potency of CYP17A1 inhibition by abiraterone. Here, we establish that abiraterone is a slow-, tight-binding inhibitor of CYP17A1, with initial weak binding preceding the subsequent slow isomerization to a high-affinity CYP17A1-abiraterone complex. The in vitro inhibition constant of the final high-affinity CYP17A1-abiraterone complex ( ( K i * = 0.39 nM )yielded a binding free energy of -12.8 kcal/mol that was quantitatively consistent with the in silico prediction of -14.5 kcal/mol. Prolonged suppression of dehydroepiandrosterone (DHEA) concentrations observed in VCaP cells after abiraterone washout corroborated its protracted CYP17A1 engagement. Molecular dynamics simulations illuminated potential structural determinants underlying the rapid reversible binding characterizing the two-step induced-fit model. Given the extended residence time (42 hours) of abiraterone within the CYP17A1 active site, in silico simulations demonstrated sustained target engagement even when most abiraterone has been eliminated systemically. Subsequent pharmacokinetic-pharmacodynamic (PK-PD) modeling linking time-dependent CYP17A1 occupancy to in vitro steroidogenic dynamics predicted comparable suppression of downstream DHEA-sulfate at both 1000- and 500-mg doses of abiraterone acetate. This enabled mechanistic rationalization of a clinically reported PK-PD disconnect, in which equipotent reduction of downstream plasma DHEA-sulfate levels was achieved despite a lower systemic exposure of abiraterone. Our novel findings provide the impetus for re-evaluating the current dosing paradigm of abiraterone with the aim of preserving PD efficacy while mitigating its dose-dependent adverse effects and financial burden. SIGNIFICANCE STATEMENT: With the advent of novel molecularly targeted anticancer modalities, it is becoming increasingly evident that optimal dose selection must necessarily be predicated on mechanistic characterization of the relationships between target exposure, drug-target interactions, and pharmacodynamic endpoints. Nevertheless, efficacy has always been perceived as being exclusively synonymous with affinity-based measurements of drug-target binding. This work demonstrates how elucidating the slow-, tight-binding inhibition of CYP17A1 by abiraterone via in vitro and in silico analyses was pivotal in establishing the role of kinetic selectivity in mediating time-dependent CYP17A1 engagement and eventually downstream efficacy outcomes.

Increased dehydroepiandrosterone (DHEA) is associated with anxiety in adolescent girls

The pubertal period is a time of rapid increase in the incidence of anxiety disorders, and thus, pubertal hormones may play a role in the precipitation of anxious psychopathology. DHEA, a steroid hormone that surges in adolescence, has been previously linked to anxiety, although the direction of this effect has been mixed. Using a cross-sectional design in a sample of 286 adolescent girls, the present study examined associations between salivary DHEA concentrations and self-report and interview-based measures of anxiety while controlling for pubertal status, menarche status, assessment time of day, and other hormones including testosterone, estradiol, and progesterone. Increased salivary DHEA concentrations were associated with more self-reported anxiety symptoms, increased anxiety symptom counts based on clinical interview, and increased probability of an anxiety disorder. Out of all anxiety symptom domains examined, generalized anxiety disorder symptoms were the best predictor of salivary DHEA concentrations after controlling for pubertal development. Collectively, our findings suggest relevance for DHEA in the development of anxiety in the pubertal period, as well as a robust relationship between DHEA and emerging symptoms of pathological worry during adolescence. The present study underscores the importance of examining associations between DHEA concentrations and anxiety in longitudinal designs.

Sex-specific associations between person and environment-related childhood adverse events and levels of cortisol and DHEA in adolescence.

Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity. We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls. A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates. Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys. We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health.

ITRAQ-based quantitative proteomic analysis of Colletotrichum lini reveals ethanol induced mechanism for enhancing dihydroxylation efficiency of DHEA

Colletotrichum lini is used as an industrial stain for the dihydroxylation of steroid compound dehydroepiandrosterone (DHEA) to biosynthesize 3β,7α,15α-trihydroxy-5-androstene-17-one (7α,15α-diOH-DHEA), a key intermediate of the most popular oral contraceptive “Yasmin”. This work aimed to enhance 7α,15α-diOH-DHEA production in C. lini CGMCC 6051 through ethanol induction. With 0.6% (v/v) ethanol induction and 10 g/L DHEA concentration, the 7α,15α-diOH-DHEA molar yield reached 58.8%, which was increased by 67.5% than that of the control. iTRAQ-based quantitative proteomic analysis was applied to explore the probable molecular mechanism of C. lini response to ethanol induction. A total of 50 differential expressed proteins was affected by ethanol induction, and could be related to multiple metabolic pathways. Most of differently expressed proteins were functionally mapped into pathways of transport, steroids metabolism, or redox reaction. Other proteins for energy, transcription and translation, and carbohydrate metabolism might have important roles in the cellular response to ethanol induction. In addition, the levels of cytochrome P450 and NAD(P)H-cytochrome P450 reductase were remarkably higher under ethanol induction, and their functions on DHEA dihydroxylation were first proposed in C. lini. Our results provide critical clues in revealing the dihydroxylation mechanism and are important for efficient microbiological hydroxylation of steroidal compounds in the future. Biological significanceiTRAQ strategy was first used to compare the proteomes of ethanol induction during the dihydroxylation reaction by Colletotrichum lini CGMCC 6051. The changes in protein provided a comprehensive overview of DHEA dihydroxylation in C. lini, including the proteins for steroids metabolism, redox reaction, transport, transcription and translation, energy and carbohydrate metabolism. Cytochrome P450, NADPH-cytochrome P450 reductase, and NADH-cytochrome b5 reductase were highlighted due to their outstanding contribution to DHEA dihydroxylation. The results help us understand the molecular mechanism underlying ethanol induction in C. lini and would guide strain engineering to further improve dihydroxylation efficiency.

MON-LB6 Association Between Sex Steroid and Metabolic Parameters in Cord Blood With Placental Fatty Acid Transporter in Obese Pregnant Women

Obesity reduces maternal insulin sensitivity and alters sex steroid serum concentrations. However, it is not clear if these changes are reflected in the fetal circulation. On the other hand, similar to other metabolic tissues, modifications in sex steroid concentrations and metabolic parameters could modify the transport and metabolism of fatty acids (FA) in the placenta increasing their availability for the fetus. Therefore, we aimed to study, in pregnant women with normal-weight and obesity, sex steroid serum concentrations in cord blood and their relationship with the gene expression of FA transporters and of molecules related with FA metabolism in the placenta. We included 26 pregnant women with normal-weight and 26 pregnant women with obesity without pregnancy complications. At term of pregnancy, mixed cord blood and placenta samples were collected and stored at -80°C. Serum concentrations of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, testosterone, estrone, estradiol, estriol, insulin and TNF-α were measured by RIA or ELISA. Glycemia and lipid profile were also analyzed. In placental samples, the gene expression of MFSD2A, CD36, FABP4, SLC27A4, PPARG, LPL and DGAT were determined by quantitative PCR. No differences were observed in sex steroid concentrations and metabolic parameters between groups. On the other hand, the gene expression of MFSD2A, CD36 and FABP4 were higher in placentas from women with obesity compared to women with normal-weight (P = 0.050, P = 0.037 and P = 0.038, respectively). When distributed according to fetal sex, cholesterol levels were higher in cord blood of women with obesity and female fetuses (P = 0.005), whereas glycemia was lower in women with obesity and male fetuses (P = 0.045). In turn, the gene expression of CD36 and FABP4 were higher (P = 0.024 and P = 0.034, respectively), whereas MFSD2A tended to be higher (P = 0.092) only in placentas from women with obesity and male fetuses. Moreover, in women with obesity and male fetuses, glycemia was positively correlated with MFSD2A (r = 0.650; P = 0.022), and in women with obesity and female fetuses FABP4 was inversely correlated with triglyceride levels (r = -0.580; P = 0.048). In conclusion, these data suggest that modifications in placental steroidogenesis do not affect sex steroid serum concentrations in the fetal circulation. On the other hand, metabolic parameters in cord blood of pregnant women with obesity are associated with an abnormal expression of FA transporters in placental tissue.

Cortisol and DHEAS Related to Metabolic Syndrome in Patients with Schizophrenia.

BackgroundBoth dehydroepiandrosterone (DHEAS) and cortisol are secreted by the adrenal glands and may modulate metabolic syndrome (MetS), which often affects the health of patients with schizophrenia. The relationship between the serum levels of these hormones and MetS has not been established.PurposeIn this pilot study, we investigated the serum levels in schizophrenia patients with and without MetS and compared them with those in healthy volunteers.Patients and MethodsAfter obtaining informed consent, 110 patients with acute paranoid schizophrenia were recruited directly after admission to the Mental Health Research Institute. The control group consisted of 51 persons reported on questioning to be mentally and somatically healthy. Blood samples to prepare serum were drawn after an 8-h overnight fast during one of the first days of admission. Serum cortisol and DHEAS concentrations were quantified by enzyme-linked immunosorbent assay.ResultsA total of 42 patients had MetS and 68 patients were without MetS. The cortisol blood level was significantly (p = 0.012) higher in schizophrenia patients without MetS in comparison to healthy controls, while patients with schizophrenia and a MetS have significantly (p = 0.014) lower DHEAS levels than healthy volunteers. These differences could, however, exclusively be attributed to female participants. Analysis of covariance adjusted for gender and age demonstrated a significant relationship between age and DHEAS levels (F = 9.512, р = 0.003).ConclusionLower DHEAS serum levels in relationship to MetS become evident in women, but not in men, and have age differences as a confounding factor.

Assessment of Cortisol and DHEA Concentrations in Griffon Vulture (Gyps fulvus) Feathers to Evaluate its Allostatic Load

Abstract The use of a non-invasive approach to collect biological samples from natural populations represents a great means of gathering information while avoiding handling animals. Even if corticosterone is the main glucocorticoid investigated in birds, there has been observed a proportional direct link between corticosterone and cortisol concentrations. Dehydroepiandrosterone (DHEA) can be produced by the adrenal cortex and should have prominent antiglucocorticoid properties also in birds. The aim of this study was to verify if there is any difference in the cortisol and DHEA feather concentrations between clinically normal and physiologically compromised Griffon vultures (Gyps fulvus) through the non-invasive approach of collecting moulted feathers without having to pluck them from the bird. The study was carried out using 8 physiologically compromised (PC) Griffons and 9 clinically normal Griffons considered as the control (CTRL) group that were necropsied or from the wildlife rehabilitation centre. Primary and secondary covert feathers were either collected directly from the birds’ cage floors, or, in the case of dead Griffons, they were plucked off the animals. The results, obtained by RIA, revealed that both cortisol (P<0.01) and DHEA (P<0.05) feather concentrations were higher in the PC than in the CTRL group. No difference was observed by comparing the cortisol/DHEA ratio between the two evaluated groups (P=0.15). Pearson’s correlation coefficients showed no correlation between feather hormone concentrations in the PC group (r=0.01, P=0.96) while a positive correlation in the CTRL group (r=0.65, P=0.006) was observed. In conclusion, our study reveals that moulted feathers can be a non-invasive and an interesting tool to evaluate the allostatic load of wild birds and they allowed better understanding the relationship between hormones of the hypothalamic–pituitary–adrenal axis and the physiological status of the birds.

Prenatal exposure to perfluorodecanoic acid is associated with lower circulating concentration of adrenal steroid metabolites during mini puberty in human female infants. The Odense Child Cohort

BackgroundFetal programming of the endocrine system may be affected by exposure to perfluoroalkyl substances (PFAAs), as they easily cross the placental barrier. In vitro studies suggest that PFAAs may disrupt steroidogenesis. “Mini puberty” refers to a transient surge in circulating androgens, androgen precursors, and gonadotropins in infant girls and boys within the first postnatal months. We hypothesize that prenatal PFAA exposure may decrease the concentrations of androgens in mini puberty. ObjectivesTo investigate associations between maternal serum PFAA concentrations in early pregnancy and serum concentrations of androgens, their precursors, and gonadotropins during mini puberty in infancy. MethodsIn the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAAs: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured at median gestational week 12 (IQR: 10, 15) in 1628 women. Among these, offspring serum concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione, 17-hydroxyprogesterone (17-OHP), testosterone, luteinizing (LH) and follicle stimulating hormones (FSH) were measured in 373 children (44% girls; 56% boys) at a mean age of 3.9 (±0.9 SD) months. Multivariate linear regression models were performed to estimate associations. ResultsA two-fold increase in maternal PFDA concentration was associated with a reduction in DHEA concentration by −19.6% (95% CI: −32.9%, −3.8%) in girls. In girls, also, the androstenedione and DHEAS concentrations were decreased, albeit non-significantly (p < 0.11), with a two-fold increase in maternal PFDA concentration. In boys, no significant association was found between PFAAs and concentrations of androgens, their precursors, and gonadotropins during mini puberty. ConclusionPrenatal PFDA exposure was associated with significantly lower serum DHEA concentrations and possibly also with lower androstenedione and DHEAS concentrations in female infants at mini puberty. The clinical significance of these findings remains to be elucidated.

Melatonin mediates seasonal transitions in aggressive behavior and circulating androgen profiles in male Siberian hamsters

Some seasonally-breeding animals are more aggressive during the short, “winter-like” days (SD) of the non-breeding season, despite gonadal regression and reduced circulating androgen levels. While the mechanisms underlying SD increases in aggression are not well understood, previous work from our lab suggests that pineal melatonin (MEL) and the adrenal androgen dehydroepiandrosterone (DHEA) are important in facilitating non-breeding aggression in Siberian hamsters (Phodopus sungorus). To characterize the role of MEL in modulating seasonal transitions in aggressive behavior, we housed male hamsters in long days (LD) or SD, treated them with timed MEL (M) or saline injections, and measured aggression after 3, 6, and 9 weeks. Furthermore, to assess whether MEL mediates seasonal shifts in gonadal and adrenal androgen synthesis, serum testosterone (T) and DHEA concentrations were quantified 36 h before and immediately following an aggressive encounter. LD-M and SD males exhibited similar physiological and behavioral responses to treatment. Specifically, both LD-M and SD males displayed higher levels of aggression than LD males and reduced circulating DHEA and T in response to an aggressive encounter, whereas LD males elevated circulating androgens. Interestingly, LD and SD males exhibited distinct relationships between circulating androgens and aggressive behavior, in which changes in serum T following an aggressive interaction (∆T) were negatively correlated with aggression in LD males, while ∆DHEA was positively correlated with aggression in SD males. Collectively, these findings suggest that SD males transition from synthesis to metabolism of circulating androgens following an aggressive encounter, a mechanism that is modulated by MEL.

Flavonoid Intake and Plasma Sex Steroid Hormones, Prolactin, and Sex Hormone-Binding Globulin in Premenopausal Women.

Background: Flavonoids potentially exert anti-cancer effects, as suggested by their chemical structures and supported by animal studies. In observational studies, however, the association between flavonoids and breast cancer, and potential underlying mechanisms, remain unclear. Objective: To examine the relationship between flavonoid intake and sex hormone levels using timed blood samples in follicular and luteal phases in the Nurses’ Health Study II among premenopausal women. Methods: Plasma concentrations of estrogens, androgens, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), prolactin, and sex hormone-binding globulin (SHBG) were measured in samples collected between 1996 and 1999. Average flavonoid were calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across categories of the intake of flavonoids and the subclasses. Results: Total flavonoid intake generally was not associated with the hormones of interest. The only significant association was with DHEAS (p-trend = 0.02), which was 11.1% (95% confidence interval (CI): −18.6%, −3.0%) lower comparing the highest vs. lowest quartile of flavonoid intake. In subclass analyses, the highest (vs. lowest) quartile of flavan-3-ol intake was associated with significantly lower DHEAS concentrations (−11.3% with 95% CI: −18.3%, −3.7%, p-trend = 0.01), and anthocyanin intake was associated with a significant inverse trend for DHEA (−18.0% with 95% CI: −27.9%, −6.7%, p-trend = 0.003). Conclusion: Flavonoid intake in this population had limited impact on most plasma sex hormones in premenopausal women. Anthocyanins and flavan-3-ols were associated with lower levels of DHEA and DHEAS.

Evaluating the effects on steroidogenesis of estragole and trans-anethole in a feto-placental co-culture model

In this study, we determined whether estragole and its isomer trans-anethole interfered with feto-placental steroidogenesis in a human co-culture model composed of fetal-like adrenocortical (H295R) and placental trophoblast-like (BeWo) cells. Estragole and trans-anethole are considered the biologically active compounds within basil and fennel seed essential oils, respectively. After a 24 h exposure of the co-culture to 2.5, 5.2 and 25 μM estragole or trans-anethole, hormone concentrations of estradiol, estrone, dehydroepiandrosterone, androstenedione, progesterone and estriol were significantly increased. Using RT-qPCR, estragole and trans-anethole were shown to significantly alter the expression of several key steroidogenic enzymes, such as those involved in cholesterol transport and steroid hormone biosynthesis, including StAR, CYP11A1, HSD3B1/2, SULT2A1, and HSD17B1, -4, and -5. Furthermore, we provided mechanistic insight into the ability of estragole and trans-anethole to stimulate promoter-specific expression of CYP19 through activation of the PKA pathway in H295R cells and the PKC pathway in BeWo cells, in both cases associated with increased cAMP levels. Moreover, we show new evidence suggesting a role for progesterone in regulating steroid hormone biosynthesis through regulation of the StAR gene.

Natural Horse Boarding Vs Traditional Stable: A Comparison of Hormonal, Hematological and Immunological Parameters

ABSTRACT In the equestrian world, two different types of management can be distinguished: traditional management and natural boarding. The aim of this research was to compare hormonal, hematological and immunological parameters of 47 horses kept in these two different managements. Blood and horsehair of the horses were sampled to determine DHEA (dehydroepiandrosterone) and cortisol concentration through RIA. Moreover, blood count was conducted, and flow cytometry was employed to phenotype lymphocyte subpopulations. Results showed that, in horsehair, DHEA concentration was significantly higher in natural horses, whereas cortisol concentration and cortisol/DEHA ratio significantly lower. These hormonal parameters are used to assess the stress condition and the welfare of animals. The most favorable endocrine framework found in horses kept in natural boarding suggests that this management conveys most with ethological and physiological needs of the species. The research underlines the need of a modification of horses’ husbandry systems. For the first time, this study validates the assay of DHEA in horsehair.

Association of endogenous DHEA/DHEAS with coronary heart disease: A systematic review and meta-analysis.

The clinical significance of dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) in coronary heart disease (CHD) has not been thoroughly elucidated to date. We performed a meta-analysis to clarify the correlations between endogenous DHEA(S) and CHD. We performed a literature search without language restriction up to August 10, 2017, and retrieved records from EMBase, PubMed, Web of Science, CNKI and WanFang databases to identify eligible cohort studies focused on the relation between DHEA(S) and CHD. A total of 26 studies were included in the systematic review and 14 case-control studies were included in the meta-analysis,which was performed using RevMan 5.1 and STATA 12. Subgroup analyses were used to discover possible sources of heterogeneity. Quality assessment was carried out using the Newcastle-Ottawa Scale. Odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression and tests for publication bias were performed. The overall average DHEAS diffusivity of CHD cases was significantly lower than that of controls with a summarized standard (std) mean difference of -0.23(95% CI, -0.45 to -0.01, P=.04). There was no association between DHEA concentration and CHD with a summarized mean difference of -0.07 (95% CI, -0.32 to 0.18, P=.59). No association was found between DHEAS concentration and arteriosclerosis patients with a summarized standard (std) mean difference of -0.46(95% CI, -0.96 to 0.04, P=.07). All of the results had a high degree of heterogeneity. The present study suggested that decreased DHEAS may be associated with coronary heart disease risk but not with arteriosclerosis. We did not find a significant association between DHEA and CHD risk.

Cardiac vagal tone, plasma cortisol, and dehydroepiandrosterone response to an ACTH challenge in lame and nonlame dairy cows

We studied the adrenocortical and vagal tone responses to a single ACTH challenge in lame (n = 9) vs nonlame (n = 9) dairy cows. Cows were paired according to parity, days in milk, and milk yield. Plasma cortisol and dehydroepiandrosterone concentrations and cardiac vagal tone response (high-frequency component of heart rate variability) were compared after intravenous ACTH administration. Baseline, minimum or maximum, amplitude of the response and area under the response curve were compared. No difference was detected between groups in the cortisol response. Dehydroepiandrosterone was irresponsive to ACTH treatment, and concentrations did not differ between lame and nonlame cows. Vagal tone decreased in response to the ACTH treatment. High frequency component of heart rate variability was lower in the lame group at all sampling times. Lameness was associated with delayed return to baseline. We concluded that the adrenal response capacity is not influenced by lameness, which supports the concept of lameness being a chronic intermittent rather than a chronically persistent stressor. Dehydroepiandrosterone concentrations were not proven to be useful indicators of hypothalamus–pituitary axis dysfunction in cattle. A decreased vagal contribution to heart rate variability—possibly coupled with increased sympathetic modulation—was observed in lame cows, which suggests that lameness affects the mechanisms underlying the action of ACTH on cardiovascular activity.

Essential oils disrupt steroidogenesis in a feto-placental co-culture model

We determined whether 5 common essential oils (basil, fennel seed, orange, black pepper and sage) interfered with feto-placental steroidogenesis in a co-culture model composed of fetal-like adrenocortical (H295R) and placental trophoblast-like (BeWo) cells. After a 24 h exposure, only basil and fennel seed oil significantly increased hormone concentrations of estradiol, estrone, dehydroepiandrosterone (DHEA), androstenedione, progesterone, and estriol. Basil and fennel seed oil were shown to significantly alter the expression of steroidogenic enzymes involved in cholesterol transport and steroid hormone biosynthesis, including StAR, CYP11A1, 3β-HSD1/2, SULT2A1, and HSD17β1, -4, and -5. Also, basil and fennel seed oil stimulated placental-specific promoter I.1 and pII-derived CYP19 mRNA in BeWo and H295R cells, respectively, as well as, increased CYP19 enzyme activity. Our results indicate that further study is necessary to determine the potential risks of using basil and fennel seed oils during pregnancy considering their potential to disrupt steroidogenic enzyme activity and expression in vitro.

Behavioral and steroidogenic pharmacology of phenyl ring substituted etomidate analogs in rats

BackgroundCushing’s syndrome is an endocrine disorder characterized by the overproduction of adrenocortical steroids. Steroidogenesis enzyme inhibitors are the mainstays of pharmacological treatment. Unfortunately, they produce significant side effects. Among the most potent inhibitors is the general anesthetic etomidate whose GABAA receptor-mediated sedative-hypnotic actions restrict use. In this study, we defined the sedative-hypnotic and steroidogenesis inhibiting actions of etomidate and four phenyl-ring substituted etomidate analogs (dimethoxy-etomidate, isopropoxy-etomidate, naphthalene-etomidate, and naphthalene (2)-etomidate) that possess negligible GABAA receptor modulatory activities.MethodsIn the first set of experiments, male Sprague-Dawley rats were assessed for loss of righting reflexes (LoRR) after receiving intravenous boluses of either etomidate (1 mg/kg) or an etomidate analog (40 mg/kg). In the second set of experiments, rats were assessed for LoRR and their abilities to produce adrenocortical and androgenic steroids after receiving 2-h infusions (0.5 mg kg− 1 min− 1) of either etomidate or an etomidate analog.ResultsAll rats that received etomidate boluses or infusions had LoRR that persisted for minutes or hours, respectively. In contrast, no rat that received an etomidate analog had LoRR. Compared to rats in the vehicle control group, rats that received etomidate analog infusions had plasma corticosterone and aldosterone concentrations that were reduced by 80–84% and 68–94%, respectively. Rats that received etomidate infusions had plasma corticosterone and aldosterone concentrations that were also significantly reduced (by 92 and 96%, respectively). Rats that received etomidate or isopropoxy-etomidate had significant reductions (90 and 57%, respectively) in plasma testosterone concentrations whereas those that received naphthalene-etomidate had significant increases (1400%) in plasma dehydroepiandrosterone concentrations. Neither etomidate nor any etomidate analog significantly affected plasma androstenedione and dihydrotestosterone concentrations.ConclusionsOur studies demonstrate that the four phenyl-ring substituted etomidate analogs form a novel class of compounds that are devoid of sedative-hypnotic activities and suppress plasma concentrations of adrenocortical steroids but vary in their effects on plasma concentrations of androgenic steroids.

The Value of Adrenal Androgens for Correcting Cortisol Lateralization in Adrenal Venous Sampling in Patients with Normal Cortisol Secretion.

The management of patients with adrenocorticotropic hormone-independent Cushing's syndrome and bilateral adrenal masses is challenging. Adrenal venous sampling (AVS) has been used to identify functional lesions in previous studies, but it is not always reliable. The present study aims to address the variability of cortisol in the adrenal veins of patients without excessive cortisol secretion and investigate the use of adrenal androgens to correct the cortisol lateralization ratio in AVS. Thirty-seven patients with primary aldosteronism underwent successful AVS. Patients with normal cortisol secretion exhibited a wide range of cortisol concentrations in the right (601-89, 400 nmol/l) and left (331-35, 300 nmol/l) adrenal veins. The median cortisol gradients between adrenal venous and peripheral venous samples were 15.25 and 10.14 in the right and left sides, respectively, and the cortisol lateralization ratio (high side to low side) was as high as 9.49 (median 1.54). The mean plasma levels of cortisol in the adrenal venous and peripheral venous samples decreased from t-15 to t0. Significant positive correlations were observed between the cortisol concentrations and both androstenedione and dehydroepiandrosterone concentrations in the right and left adrenal veins. After correcting for androstenedione or dehydroepiandrosterone levels, the cortisol lateralization ratio was less than 2 in most adrenal venous samples. The present study demonstrated the wide variation in cortisol concentrations in the adrenal veins of patients with normal cortisol secretion. The adrenal androgens might be ideal analytes used as normalizers when assessing the cortisol lateralization of AVS in normal or hypercortisolism cases.

Cortisol, DHEA, and Sexual Steroid Concentrations in Fattening Pigs' Hair.

Simple SummaryThe rearing of heavy pigs in Italy is an important part of the production of Protected Designation of Origin (PDO) hams. Along with the standard quality characteristics, the quality of products with animal origin is also assessed by the level of animal welfare. Evaluation of hair steroid concentrations has been considered an effective approach to assess stress in mammals. The advantage of using hair for this process is that it provides an integrated measure of hormone concentrations over medium- and long-term periods, it can be simply and non-invasively collected, and it does not require any special expedient for storage. The aim of this study was to evaluate the hair cortisol, dehydroepiandrosterone (DHEA), and sexual steroid concentrations in fattening pigs at 36 weeks of age before slaughtering through a non-invasive approach. Females had significantly higher cortisol levels, significantly lower concentrations of DHEA, and significantly higher cortisol/DHEA ratios than barrows. Progesterone was significantly higher in gilts than in barrows. Testosterone and 17β-estradiol were significantly higher in barrows than in gilts. These results will allow us to plan future research with the aim of identifying threshold values in order to set up strategies to control the allostatic load and to increase the resilience of fattening pigs.The aim of this study was to analyze the feasibility and reliability of using hair as a matrix to determine the dehydroepiandrosterone (DHEA) and sexual steroid concentrations and the cortisol/DHEA ratio in fattening pigs. The results could be also used to plan future research to identify threshold values in order to set up strategies to control the allostatic load and increase the resilience of fattening pigs before slaughter. The study was conducted on 107 commercial crossbred rearing pigs. The hair samples were taken by shaving at the age of 36 weeks, and concentrations of the hormones were measured using a solid-phase microtiter radioimmunoassay. Females had significantly higher cortisol levels (p < 0.01), significantly lower DHEA concentrations (p < 0.05) and significantly higher cortisol/DHEA ratios (p < 0.01) than barrows. Progesterone was significantly higher in gilts than in barrows (p < 0.01). Testosterone and 17β-estradiol were significantly higher in barrows than in gilts (p < 0.05). If future research can produce threshold values for the different markers examined, the evaluation of animals under subclinical stress conditions will be possible.

SUN-376 Isolated DHEA-S Production by an Adrenal Neoplasm: Clinical, Biochemical, and Pathologic Findings

Background. Pure androgen secreting adrenal neoplasms are rare and present with virilization, including hirsutism (face, chest, and back), male pattern baldness, acne, deepening of the voice and clitoral enlargement. Serum concentrations of testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione are elevated (1,2). To our knowledge, an adrenal neoplasm with isolated DHEA-S production and otherwise normal androgens has not been reported. We report the clinical, biochemical, and pathologic features of a pure DHEA-S secreting adrenal neoplasm occurring in a post-menopausal woman. Clinical case. A 57 y/o post-menopausal Indian female presented with a 4 cm right adrenal mass found on CT imaging for colitis. She denied any dietary supplements containing DHEA or DHEA-S. She reported generalized hair thinning. She denied deepening of voice, excessive hair growth, or acne. Physical examination confirmed these reports; there was no clitoromegaly. Biochemical testing revealed an elevated (mean of 2 measurements) serum DHEA-S concentration of 706 mcg/dL (nl = 26-200). Other serum androgen concentrations were normal and included free testosterone = 2.3 pg/mL (nl = 0.6-3.8 ); DHEA = 2.41 ng/mL(nl = 0.60-5.73); and androstenedione = 0.529 ng/mL (nl = 0.130-0.820 ). Other circulating adrenal hormone concentrations including cortisol, aldosterone, estrone, estradiol, and metanephrines were normal. ACTH was not suppressed, and FSH and LH were appropriately elevated for the post-menopausal state. CT imaging revealed a heterogeneous 4 cm right adrenal mass that contained several areas measuring <10 HU. The mass was excised by uncomplicated laparoscopic adrenalectomy. The tumor size was 5.0 x 4.5 x 2.5 cm. Pathology revealed an adrenal cortical neoplasm that was likely benign, since the mitotic rate was low. At 24 h post adrenalectomy, serum DHEA-S concentration had decreased to 274 mcg/dL. Three weeks post adrenalectomy, DHEA-S was normal at 91 mcg/dL. Other serum androgen concentrations decreased slightly post-operatively. Summary: The rapid decrease in the elevated serum DHEA-S concentration following adrenalectomy confirmed DHEA-S production by the pathologically benign 5.0 cm adrenal adenoma. Biochemical testing was negative for production of other adrenal hormones, and the only clinical feature was nonspecific generalized hair thinning. Conclusion: We describe the clinical, biochemical, and pathologic findings of an exceedingly rare adrenal neoplasm with isolated DHEA-S production. References. (1)F. Cordera, et al., Surgery, 134 (6): 874-880, 2003. (2)Moreno, S., et al, Surgery, 136(6): 1192-1198, 2004.