Dehydroepiandrosterone Concentrations Research Articles

Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities

BackgroundOrganophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. MethodsIn 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17β-estradiol, and cortisol. We used general linear models to assess linear (β = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (β2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. ResultsThe organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (βboys = 5.88% [1.21%, 10.78%], βgirls = 4.10% [-0.02%, 8.39%]), and cortisol (βboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (β2boys = −0.17 (−0.33, −0.003), p = 0.04) and DHEA (β2boys = −0.49 (−0.80, −0.19), p = 0.001) in boys. The neonicotinoid summary score (βboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (βboys = 3.90% [1.28%, 6.58%]) were positively associated with 17β-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. ConclusionsWe observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17β-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Effect of age on androgens pattern in cyclic mares

Androgens are produced in both sexes. In females produced by the adrenal gland and the ovaries they play a crucial role in regulating ovarian function, estrogen synthesis and follicular growth. Age leads to a reduction in androgen concentrations, although, at present, these mechanisms are not elucidated in mares. The objective of this study was to evaluate the concentrations of testosterone (T), androstenedione (A4) and dehydroepiandrosterone (DHEA) in mares of different ages. Blood samples were drawn from seventy cyclic Spanish Purebred mares belonging to five age groups: 3–5 years, 6–9 years, 10–13 years, 14–16 years and > 16 years. The concentrations of T, A4 and DHEA were determined by EIA, validated specifically for horses. Mares aged 3–5, 6–9 and 10–13 years had higher T concentrations (P < 0.05) than mares aged >16 years, and mares aged 6–9 years had also higher concentrations than those 14–16 years old (P < 0.05). A4 concentrations were lower (P < 0.05) in mares >16 years old when compared with those of other age groups. DHEA concentrations were lower (P < 0.05) in mares 14–16 years and > 16 years old when compared with those of other age groups. DHEA was positively correlated with T (r = 0.61; P < 0.05) and A4 (r = 0.51; P < 0.05). Age induces reduction in androgens' synthesis in physiologically cyclic Spanish Purebred mares. These physiological variations must be duly considered for a correct and objective interpretation of the analytical data.

Examining parental stress and its link to hair cortisol and DHEA levels in kindergartners

Background Parental work-family conflict (WFC) and parental household income have been linked to negative outcomes for children. So far, no study has associated these two stressors with the hair concentration of cortisol (HCC) and dehydroepiandrosterone (DHEA) in kindergarteners as a measurement of their objective stress. Methods and measures 44 children (40.91% female) with a mean age of 5.16 years and their parents participated in this cross-sectional study. Children’s cortisol and DHEA measurements reflected the hormones produced over the past two months. Parents filled out questionnaires concerning their WFC and parenting behavior. Results Higher maternal WFC and a lower parental net household income were negatively associated with the DHEA and positively with HCC/DHEA ratio of their children. No significant associations were found between HCC and any included variables. Paternal WFC had no impact on the stress hormones and negatively affected parenting behavior of both parents. Levels of stress hormones were not correlated with parenting behavior. Conclusion The present results indicated a higher stress exposure in children of mothers with a higher WFC and lower net household income. Conceivably, this may have led to an accumulation of allostatic load. Potential influences of demographic variables on the children’s hormones are discussed.

Serum levels of the steroid hormone dehydroepiandrosterone (DHEA) are associated with psychological trauma and lymphocyte telomere integrity in women suffering from depression.

Emerging studies highlight the telomere system as an aging mechanism underlying the association between exposure to psychological trauma and the development of a wide range of physical and mental disorders, including major depressive disorder (MDD). Here, we investigated associations of circulating levels of the steroid hormone dehydroepiandrosterone (DHEA) with immune cell telomere length (TL) in the context of lifetime trauma exposure and MDD. Lifetime traumatic events (trauma load) were assessed using the Essener Trauma Inventory (ETI) in n=22 postmenopausal female inpatients with MDD and n=22 non-depressed controls. All women completed the Beck's Depression Inventory-II to assess the severity of current depressive symptoms. DHEA concentration in serum was measured by immunoassay and TL was quantified in kilobase units using quantitative fluorescent in situ hybridization (qFISH) in total peripheral blood mononuclear cells (PBMC) and in selected T cell subpopulations isolated by FACS separation. Higher trauma load was significantly associated with lower DHEA concentration, which in turn was linked to more depression-related fatigue. Furthermore, DHEA concentration was positively and significantly associated with TL in memory CD4+ T cells as well as in naïve and memory CD8+ T cells, but not in naïve CD4+ T cells and total PBMC. Mediational analysis suggested that DHEA concentration is a mediator in the relationship between trauma load and memory CD8+ T cell TL. The current findings suggest a potential role of DHEA as a biological resilience factor that may exert beneficial effects on telomere integrity, especially in conditions related to distress.

In and out Beauty and Sensitive Skin, a Psychophysiological Exploration: Myth or Reality?

Knowing that biomolecules, such as β-amyrin and α-amyrin, have some pharmacological effects, the aim of this study was directed towards exploring the protective effect of Tomato Peel and Seed Extract (TPSE) for its soothing function but also for its capacity to modulate the adrenal axis, which is involved in stress response. Ex vivo tests were carried out on skin explants to evaluate the effectiveness of TPSE formulated at 0.5% on Calcitonin Gene-Related Peptide (CGRP) and IL-10 release, Kappa Opioid Receptor (KOR), and Caspase 14 expression. An in vivo study combined a clinical evaluation of skin homogeneity and psychological parameters as well as an analysis of salivary cortisol and dehydroepiandrosterone concentrations. All measurements were carried out at the beginning and after 28 days of applying a TPSE face cream. TPSE regulated not only the release of CGRP, IL-10, and the expression of Caspase 14, reflecting anti-neurogenic and anti-inflammatory properties, but also modulated KORs. Twenty-eight days of TPSE application induced a significant decrease in intensity and extent erythrosis, a lower output of salivary cortisol, and a significant increase in pleasant emotions when compared to placebo. These results provide encouragement to continue exploring the impact of cosmetic ingredients on psychophysiological parameters to improve skin health and well-being.

Sex-steroid hormones and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways. This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders. Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05). Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.

Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women.

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96-2.92, ptrend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96-3.30, ptrend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28-1.05, ptrend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.

132 Genetics of Stress Hormone Concentrations in Hair of Healthy Nursery Pigs and Their Relationship with Back Test Responses

Abstract Cortisol and dehydroepiandrosterone (DHEA) are circulating adrenal hormones whose concentration in the blood varies in the face of infectious and non-infectious stressors. Their incorporation into hair makes their concentration in hair a robust retrospective assessment of HPA-axis activity as a measure of the stress response of an animal over the period of hair growth. Our objective was to estimate the genetic parameters of hormone concentrations in the hair of healthy pigs and their genetic correlation with responses to the standard back-test. Hair shaved from the rump area of 871 Large White X Landrace barrows (~40 d of age) from 6 breeding companies, maintained in a high-health nursery, was analyzed for cortisol and DHEA concentrations. Behavioral responses to a 60 s standard back-test were obtained at ~26 d of age, including the number of vocalizations (VN) and struggles (SN) and the intensity of the vocalizations (VI) and struggles (SI). All pigs were genotyped with a 50K SNP panel and imputed up to 650K. Estimates of heritability of log-transformed levels of cortisol and DHEA using univariate animal models were 0.26 ± 0.08 and 0.00, respectively, while litter effects explained 0.19 ± 0.05 and 0.09 ± 0.04 of the phenotypic variance, respectively. Back-test responses were more heritable, ranging from 0.34 ± 0.08 (VI) to 0.58 ± 0.08 (VN), with small litter effects (0.00 to 0.06). Estimates of genetic correlations using bivariate animal models were high among the back-test responses, ranging from 0.58 ± 0.16 for SN-VN to 0.96 ± 0.04 for VN-VI and 0.99 ± 0.10 for SN-SI. Estimates of genetic correlations of cortisol with back-test responses ranged from low (0.08 ± 0.23 with SI) to moderate (0.66 ± 0.27 with SN). We conclude that the concentration of cortisol in the hair of healthy nursery pigs is a heritable molecular phenotype and is genetically correlated with responses to the back-test. In subsequent research, their potential as indicator traits to select for disease resilience will be investigated. This study was funded by Genome Canada, PigGen Canada, and USDA-NIFA grant # 2021-67015-34562.

RNA-Seq reveals ACTH-induced steroid hormone pathway participating in goat adrenal gland response to castration

The content of androgen from adrenal is elevated under castration, and the mechanisms of compensatory secretion of adrenal androgen remain unknown. This study was designed to compare the transcript profiles between adrenals from noncastrated, orchiectomized and immunocastrated Yiling goats. Fifteen goats were randomly divided into three groups: pVAX-asd injection (control) group, pVAX-B2L-(G4S)3-kisspeptin-54-asd immunization (PBK-asd) group, and surgical castration (SC) group. Subsequently, serum was collected every two weeks after the initial immunization for hormone assays. At week 14 after immunization, adrenal glands were collected for transcriptome sequencing and qPCR. Serum testosterone concentration was significantly reduced in PBK-asd and SC group, demonstrating the effectiveness of castration. Both surgical and immunized castration resulted in adrenal hyperplasia, and thickness of adrenal cortex elevated. The specific genes involving castration were enriched in many pathways, including Steroid hormone biosynthesis pathway. The adrenocorticotropic hormone (ACTH), which promotes the production of adrenal steroids, and dehydroepiandrosterone (DHEA), a steroid hormone secreted by adrenal glands, both increased after castration. Further construction of co-expression network for transcription genes and traits (including adrenal weight and cortex thickness, ACTH and DHEA concentration) showed that the trait-related genes were enriched in multiple steroid-related pathways. These results showed that adrenal compensatory hyperplasia and androgen secretion caused by castration may involve in ACTH-induced steroid hormone synthesis.

DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA.

Malaria is the most lethal parasitic disease worldwide; the severity of symptoms and mortality are higher in men than in women, exhibiting an evident sexual dimorphism in the immune response; therefore, the contribution of 17β-estradiol and testosterone to this phenomenon has been studied. Both hormones differentially affect several aspects of innate and adaptive immunity. Dehydroepiandrosterone (DHEA) is the precursor of both hormones and is the sexual steroid in higher concentrations in humans, with immunomodulatory properties in different parasitic diseases; however, the involvement of DHEA in this sexual dimorphism has not been studied. In the case of malaria, the only information is that higher levels of DHEA are associated with reduced Plasmodium falciparum parasitemia. Therefore, this work aims to analyze the DHEA contribution to the sexual dimorphism of the immune response in malaria. We assessed the effect of modifying the concentration of DHEA on parasitemia, the number of immune cells in the spleen, cytokines, and antibody levels in plasma of CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). DHEA differentially affected the immune response in males and females: it decreased IFN-γ, IL-2 and IL-4 concentrations only in females, whereas in gonadectomized males, it increased IgG2a and IgG3 antibodies. The results presented here show that DHEA modulates the immune response against Plasmodium differently in each sex, which helps to explain the sexual dimorphism present in malaria.

Temperature and humidity index (THI) affects salivary cortisol (HC) and dehydroepiandrosterone (DHEA) concentrations in growing bulls following stress generated by performance test procedures.

The hypothalamus-pituitary-adrenal axis response to a challenge was proposed for genetic selection of robust and resilient animals. As ACTH (adrenocorticotropic hormone) test and hormone measurements in blood may result impractical, it may be useful to measure salivary hormones in response to natural stressors, after an accurate biological validation, to control factors that could contribute to the response. We evaluated whether animal handling during performance test affects salivary HC and DHEA secretion and could be used for selection. We tested the effects of habituation to repeated handling and THI as putative bias. Bull calves (N = 273) undergoing performance test were sampled at 8-9 and 11-13 months (N = 101), 8-9 months (N = 131), or 11-13 months (N = 41). On each test day (D0), calves were isolated, conducted to a squeeze chute and immobilized for 6 min. Saliva samples were collected in the morning after feed administration (T0), and after 6 min immobilization in the squeeze chute (T1) for HC and DHEA measurement. Environmental temperature and relative humidity were recorded every hour from 1:00 h to 24:00 h during the 6 days before the performance test and on D0. Salivary HC and DHEA concentrations were higher in T1 (p < 0.01), although a clear individual positive response to handling could be observed in less than 10% of subjects. The mixed model revealed: (i) HC and HC/DHEA were higher in Young bulls (p < 0.05). (ii) The time of T0 sample collection significantly affected DHEA (p < 0.01) and HC/DHEA (p < 0.05). (iii) THI affected both steroids (p < 0.001) but not HC/DHEA. Spearman correlations suggested that THI weakly affected salivary HC at T0 only (ρ = 0.150, p < 0.01), while moderate statistically significant correlations were found between DHEA and THI at T0 (ρ = 0.316, p < 0.001), and T1 (ρ = 0.353, p < 0.001). Salivary HC and DHEA in response to handling procedures might identify subpopulations of subjects with sensitive HPA axis. Habituation to repeated handling played a role, as the hormone response was lower in older animals. Chronic exposure to high THI had a minor effect on salivary HC visible at T0. A more intense THI effect was observed on salivary DHEA concentrations at both T0 and T1, which should be worth of further investigations.

Stimulatory and Inhibitory Effects of Steroid Hormones and Human Cytochrome P450 (CYP) 3A Inhibitors on Cortisol 6β-Hydroxylation Catalyzed by CYP3A Subfamilies.

The inhibitory and stimulatory effects of several compounds, including steroid hormones and azole antifungal agents, on cortisol 6β-hydroxylation activity by cytochrome P450 (CYP) 3A4, polymorphically expressed CYP3A5, and fetal CYP3A7 were compared with those on testosterone 6β-hydroxylation to clarify the catalytic properties of the predominant forms of the human CYP3A subfamily. 6β-Hydroxylation activities of cortisol and testosterone by CYP3A4, CYP3A5, and CYP3A7 in the absence or presence of dehydroepiandrosterone (DHEA), α-naphthoflavone (ANF), ketoconazole, itraconazole, and voriconazole were measured using high-performance liquid chromatography. Lower concentrations of DHEA and ANF increased cortisol 6β-hydroxylation activities catalyzed by CYP3A4 but not those catalyzed by CYP3A5 and CYP3A7. The inhibition strength of azole antifungal agents against cortisol 6β-hydroxylation catalyzed by all CYP3A subfamilies was similar to that of testosterone 6β-hydroxylation. Although the Michaelis constant (Km) increased 2-fold in the presence of 20 μM DHEA compared to that of the control, the maximal velocity (Vmax) values gradually increased with increasing DHEA. For ANF, both Km and Vmax values increased, although the Km value decreased at 2.5 μM concentrations. Ketoconazole and itraconazole competitively inhibited cortisol 6β-hydroxylation mediated by CYP3A4 with similar inhibition constants. The inhibitory/stimulatory pattern among CYP3A subfamily members differed between cortisol and testosterone, and CYP3A4 was found to be the most sensitive in terms of inhibition by azole antifungals among the CYP3A subfamily members investigated.

Comparative steroid profiling of newborn hair and umbilical cord serum highlights the role of fetal adrenals, placenta, and pregnancy outcomes in fetal steroid metabolism

Previous steroid hormone studies concerning pregnancy and newborns have mainly focused on glucocorticoids; wider steroid profiles have been less commonly investigated. Here, we performed a comparative analysis of 17 steroids from newborn hair and umbilical cord serum at the time of delivery. The study participants (n = 42, 50% girls) were a part of the Kuopio Birth Cohort and represent usual Finnish pregnancies. The hair and cord serum samples were analyzed with liquid chromatography high resolution mass spectrometry and triple quadrupole tandem mass spectrometry, respectively. We detected high individual variations in steroid hormone concentrations in both sample matrices. The concentrations of cortisol (F), corticosterone (B), estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), 11β-hydroxyandostenedione (11bOHA4), 5α-androstanedione (DHA4), and 17α-hydroxypregnenolone (17OHP5) correlated positively between cord serum and newborn hair samples. In addition, F and 11bOHA4 concentrations correlated positively with each other in both newborn hair and cord serum samples. The cortisone-to-cortisol ratio (E/F) was significantly higher in cord serum than in newborn hair samples reflecting high placental 11βHSD2 enzyme activity. Only minor sex differences in steroid concentrations were observed; higher testosterone (T) and 11-deoxycortisol (S) with lower 11bOHA4 in male cord serum, and higher DHEA, androstenedione (A4) and 11bOHA4 in female newborn hair samples. Parity and delivery mode were the most significant pregnancy- and birth-related parameters associating with F and some other adrenocortical steroid concentrations. This study provides novel information about intrauterine steroid metabolism in late pregnancy and typical concentration ranges for several newborn hair steroids, including also 11-oxygenated androgens.

3βHSD activity saturates at physiological substrate concentrations in intact cells.

Conversion of adrenally produced dehydroepiandrosterone (DHEA) to the potent androgen dihydrotestosterone (DHT) is an important mechanism by which prostate cancer reaches castration resistance. At the start of this pathway is a branch point at which DHEA can be converted to Δ4 -androstenedione by the enzyme 3β-hydroxysteroid dehydrogenase (3βHSD) or to Δ5 -androstenediol by 17βHSD. To better understand this process, we studied the kinetics of these reactions in cells. Prostate cancer cells (LNCaP cell line) were incubated with steroids (DHEA and Δ5 -androstenediol) over a range of concentrations and the steroid metabolism reaction products were measured by mass spectrometry or by high-performance liquid chromatography to determine reaction kinetics. To confirm the generalizability of results, experiments were also performed in JEG-3 placental choriocarcinoma cells. The two reactions displayed very different saturation profiles, with only the 3βHSD-catalyzed reaction beginning to saturate within a physiological substrate concentration range. Strikingly, incubating LNCaP cells with low (in the ~10 nM range) concentrations of DHEA resulted in a large majority of the DHEA undergoing 3βHSD-catalyzed conversion to Δ4 -androstenedione, whereas high concentrations of DHEA (in the 100s of nM range) resulted in most of the DHEA undergoing 17βHSD-catalyzed conversion to Δ5 -androstenediol. Contrary to expectations from previous studies that used purified enzyme, cellular metabolism of DHEA by 3βHSD begins to saturate in the physiological concentration range, suggesting that fluctuations in DHEA concentrations could be buffered at the downstream active androgen level.

Cortisol and DHEA as markers of placentitis in pregnant mares: a preliminary study

Placentitis in mares is a subclinical cause of abortion, highlighting the importance of early detection for successful treatment. Sexual steroids could serve as biomarkers, but cross-reactivity and a limited detection range of immunoassays may hinder accurate measures. This study evaluated some steroids as potential markers of placentitis using liquid chromatography coupled to mass spectrometry (LC-MS), known to improve detection and quantification of steroids with good selectivity, specificity, and allowing multiplexing capabilities (Conley et al., Reproduction. 2019;158:197-208; Ledeck et al., Theriogenology. 2022;189:86-91). From the 7th month of pregnancy, mares were transrectally scanned to measure the combined thickness of the uterus and placenta (CTUP), and blood samples were collected at a fixed time of day. Ten healthy mares (HM) and nine mares diagnosed with non-experimentally-induced placentitis (PM) between 8 and 10 months were enrolled, based on ultrasonographic placentitis signs: heterogeneous echogenicity and/or thickened CTUP. Post-partum allantochorion examination confirmed the diagnosis. Subsequently, PM were further excluded from the study as they received treatments for placentitis. Serum concentrations of progesterone, 17α-hydroxyprogesterone (17αOHP), dehydroepiandrosterone (DHEA), and cortisol were assayed using LC-MS. Non-normally distributed data were presented as medians, and groups were compared at the same month of pregnancy using the Mann-Whitney test. There were no significant differences in 17αOHP and progesterone concentrations between groups at any month.DHEA concentrations were significantly higher (p=0.0297) at 8 months in PM (3.552μg/L) compared to HM (2.240μg/L). A similar trend was observed at 9 months, with DHEA concentrations of 2.126μg/L and 1.445μg/L in PM and HM, respectively (p=0.0604). In contrast, HM had significantly higher (p=0.022) cortisol concentrations at 7 months (71.75μg/L) compared to PM (38.62μg/L). This difference tended (p=0.0529) to be observed at 8 months with cortisol concentrations of 52.25μg/L (HM) and 37.28μg/L (PM). The DHEA/cortisol ratio was significantly higher in PM than in HM at 9 months (p=0.013) and tended to be increased at 7 and 8 months (respectively, p=0.0659 and p=0.0529). Placentitis has been shown to increase pregnenolone production (Ousey et al., Theriogenology. 2005;63:1844-1856). In this preliminary study, PM were observed to metabolize pregnenolone into DHEA rather than cortisol, without changes in 17αOHP concentrations. Reduced cortisol concentrations at 7 months could be an early but non-specific biomarker of placentitis. Conversely, elevated DHEA Ievels only appear together with ultrasonographic signs at 8 months but could become a more specific biomarker, which differs from previous findings in mares with experimentally-induced placentitis (Canisso et al., Equine Veterinary Journal. 2017;49:244-249). These changes result in a higher DHEA/cortisol ratio in PM at 9 months. However, further research should explore modifications of steroids’ pathways in PM to confirm the value of DHEA and cortisol for early diagnosis of placentitis in mares.

Hair cortisol, cortisone and DHEA concentrations and the composition of microbiota in toddlers

Animal research suggests that the gut microbiota and the HPA axis communicate in a bidirectional manner. However, human data, especially on early childhood, remain limited. In this exploratory design, we investigated the connections between long-term HPA axis functioning, measured as cortisol, cortisone or dehydroepiandrosterone concentrations and their ratios from hair segments of three centimeters, and gut microbiota profiles, (measured as diversity and bacterial composition by 16 S rRNA sequencing) in healthy 2.5-year-old toddlers (n = 135) recruited from the FinnBrain Birth Cohort Study. The alpha diversity of the microbiota was studied by linear regression. Beta diversity analyses with weighted UniFrac or Bray-Curtis distances were performed using PERMANOVA. The bacterial core genus level analyses were conducted using DESeq2 and ALDEx2. These analyses suggested that hair sample concentrations of separate hormones, cortisol/cortisone and cortisol/dehydroepiandrosterone ratios were associated with various gut bacterial genera such as the Veillonella, the [Ruminococcus] torques group and [Eubacterium] hallii group, although multiple testing correction attenuated the p-values. Alpha or beta diversity was not linked with either steroid concentrations or ratios. These findings in toddlers suggest that long-term HPA axis activity may be related to genera abundancies but not to ecosystem-level measures in gut microbiota. The influence of these observed interrelations on later child health and development warrants further research.

Who benefits most from a prenatal HEPA filter air cleaner intervention on childhood cognitive development? The UGAAR randomized controlled trial

BackgroundAir pollution exposure during pregnancy affects children's brain function. Maternal stress and nutrition, socioeconomic status, and the child's sex may modify this relationship. ObjectiveTo identify characteristics of children with the largest increases in full-scale IQ (FSIQ) after their mothers used HEPA filter air cleaners during pregnancy. MethodsIn this randomized controlled trial we randomly assigned women to receive 1–2 air cleaners or no air cleaners during pregnancy. We analyzed maternal hair samples for cortisol and dehydroepiandrosterone (DHEA). When the children were 48 months old, we measured FSIQ with the Wechsler Preschool and Primary Scale of Intelligence. We evaluated ten potential modifiers of the intervention-FSIQ relationship using interaction terms in separate regression models. To account for correlations between modifiers, we also used a single regression model containing main effects and intervention x modifier terms for all potential modifiers. ResultsAmong 242 mother-child dyads with complete data, the intervention was associated with a 2.3-point increase (95% CI: −1.5, 6.0 points) in mean FSIQ. The intervention improved mean FSIQ among children of mothers in the bottom (5.4 points; 95% CI: −0.8, 11.5) and top (6.1 points; 95% CI: 0.5, 11.8) cortisol tertiles, but not among those whose mothers were in the middle tertile. The largest between-group difference in the intervention's effect was a 7.5-point (95% CI: −0.7, 15.7) larger increase in mean FSIQ among children whose mothers did not take vitamins than among children whose mothers did take vitamins (interaction p-value = 0.07). We also observed larger benefits among children whose mothers did not complete university, and those with lower hair DHEA concentrations, hair cortisol concentrations outside the middle tertile, or more perceived stress. ConclusionThe benefits of reducing air pollution during pregnancy on brain development may be greatest for children whose mothers who do not take vitamins, experience more stress, or have less education.

Sow's pre- and post-delivery in different confinement systems evaluated by hair hormones concentrations

Several matrices are available to detect the concentrations of cortisol and dehydroepiandrosterone (DHEA) as markers of allostatic load and resilience but most of them provide a measurement of the concentration at a single-time point or within a 12– 24 h period and are subjected to daily fluctuations; conversely, keratinized derivatives, as hair is, provide a measure of the hormonal concentrations over medium- and long-term periods, appearing unaffected by circadian changes or by factors inducing short-term variations. Aim of this study was to evaluate hair cortisol (HC), hair DHEA (HDHEA) and their ratio (HC/HDHEA ratio) as biomarkers of allostatic load and resilience in sows around farrowing, in relation to four different models of farrowing crates, and in relation to different batches by a non-invasive sampling. The study has been conducted on 296 pregnant sows managed in a batch farrowing system from February to June. Sows were kept in multiple pens of 10–15 sows until 5 days before farrowing, then were randomly divided in 4 different models of farrowing crates. The hair samples were taken by shaving for the first time (ST1) 2.6 ± 1.6 days before the expected delivery date and for the second time (ST2) 88.9 ± 3.3 days after parturition. The environmental temperature and the relative humidity data were recorded and used to calculate the Temperature Humidity Index (THI). HC and HDHEA were determined using a solid-phase microtiter radioimmunoassay (RIA) while HC/HDHEA ratio has been calculated. No differences in terms of hair steroids concentration were found between the four models of farrowing crates and the sampling times (P > 0.05). The interaction between batch and sampling time has been significant for all the biomarkers considered (HC (P < 0.01), HDHEA (P < 0.05) and their ratio (P < 0.01)). During the pregnancy period in collective pens (ST1) HC/HDHEA ratios were never lower (with an exclusion of February) than those in the following characterized by the early postpartum and lactation in individual crates (ST2). It seems that an aggregate effect of different stressors acts on the sows exhausting their ability to cope with adverse events; it should be further investigated the influence of the social interaction in collective pens that cyclically re-occurs in the standard swine production system.

Mechanism of leptin-NPY on the onset of puberty in male offspring rats after androgen intervention during pregnancy.

The time of onset of puberty has been increasingly earlier, but its mechanism is still unclear. This study aimed to reveal the mechanism of leptin and NPY in the onset of puberty in male offspring rats after androgen intervention during pregnancy. Eight-week-old specific pathogen-free (SPF) healthy male Sprague-Dawley (SD) rats and 16 female SD rats were selected and caged at 1:2. The pregnant rats were randomly divided into the olive oil control group (OOG) and testosterone intervention group (TG), with 8 rats in each group. Olive oil and testosterone were injected from the 15th day of pregnancy, for a total of 4 injections (15th, 17th, 19th, 21st day). After the onset of puberty, the male offspring rats were anesthetized with 2% pentobarbital sodium to collect blood by ventral aorta puncture and decapitated to peel off the hypothalamus and abdominal fat. Serum testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and leptin were detected by ELISA, and then the free androgen index (FAI) was calculated. The mRNA levels of androgen receptor (AR), estrogen receptor α (ERα), NPY, leptinR, and NPY2R in the hypothalamus and abdominal fat were detected by RT-PCR. Protein expression levels of AR, ERα, NPY, leptinR, and NPY2R in the arcuate nucleus (ARC) of the hypothalamus were detected by immunohistochemistry. The time of onset of puberty was significantly earlier in the TG than in the OOG (P< 0.05) and was positively correlated with body weight, body length, abdominal fat, and leptinR mRNA levels in adipose tissue in the OOG (P< 0.05), while it was positively correlated with serum DHT and DHEA concentrations and FAI and AR mRNA levels in the hypothalamus in the TG (P< 0.05). The NPY2R mRNA level and protein expression levels of ERα, NPY2R, and leptinR in the TG were significantly higher than those in the OOG, while the protein expression levels of AR and NPY in the TG were significantly lower than those in the OOG (P< 0.05). Testosterone intervention during pregnancy led to an earlier onset of puberty in male offspring rats, which may render the male offspring rats more sensitive to androgens, leptin, and NPY at the onset of puberty.

Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project

Background & AimsIncidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. MethodsConcentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. ResultsHigher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). ConclusionsHigher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implicationsThis study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.