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International Journal of Cancer Apr 2022Biomarkers for early detection of pancreatic cancer are in urgent need. To explore systematic circulating metabolites unbalance and identify potential biomarkers for...
Biomarkers for early detection of pancreatic cancer are in urgent need. To explore systematic circulating metabolites unbalance and identify potential biomarkers for pancreatic cancer in prospective Chinese cohorts, we conducted an untargeted metabolomics study in subjects with incident pancreatic cancer and matched controls (n = 192) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We characterized 998 metabolites in baseline serum and calculated 156 product-to-precursor ratios based on the KEGG database. The identified metabolic profiling revealed systematic metabolic network disorders before pancreatic cancer diagnosis. Forty-Five metabolites or product-to-precursor ratios showed significant associations with pancreatic cancer (P < .05 and FDR < 0.1), revealing abnormal metabolism of amino acids (especially alanine, aspartate and glutamate), lipids (especially steroid hormones), vitamins, nucleotides and peptides. A novel metabolite panel containing aspartate/alanine (OR [95% CI]: 1.97 [1.31-2.94]), androstenediol monosulfate (0.69 [0.49-0.97]) and glycylvaline (1.68 [1.04-2.70]) was significantly associated with risk of pancreatic cancer. Area under the receiver operating characteristic curves (AUCs) was improved from 0.573 (reference model of CA 19-9) to 0.721. The novel metabolite panel was validated in an independent cohort with AUC improved from 0.529 to 0.661. These biomarkers may have a potential value in early detection of pancreatic cancer.
Topics: Aged; Biomarkers, Tumor; Female; Humans; Male; Metabolic Networks and Pathways; Metabolomics; Middle Aged; Pancreatic Neoplasms; Prospective Studies
PubMed: 34792202
DOI: 10.1002/ijc.33877 -
Life (Basel, Switzerland) Apr 2024Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR)... (Review)
Review
Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.
PubMed: 38792602
DOI: 10.3390/life14050582 -
Molecules (Basel, Switzerland) Jan 2020Steroidal glycosides are important sources of innovative drugs. The increased diversification of steroidal glycosides will expand the probability of discovering active...
Steroidal glycosides are important sources of innovative drugs. The increased diversification of steroidal glycosides will expand the probability of discovering active molecules. It is an efficient approach to diversify steroidal glycosides by using steroidal glycosyltransferases. OcUGT1, a uridine diphosphate-d-glucose (UDP-Glc)-dependent glycosyltransferase from , is a multifunctional enzyme, and its glycodiversification potential towards steroids has never been fully explored. Herein, the glycodiversification capability of OcUGT1 towards 25 steroids through glucosylation and transglucosylation reactions were explored. Firstly, each of 25 compounds was glucosylated with UDP-Glc. Under the action of OcUGT1, five steroids (testosterone, deoxycorticosterone, hydrocortisone, estradiol, and 4-androstenediol) were glucosylated to form corresponding mono-glucosides and biosides. Next, OcUGT1-mediated transglucosylation activity of these compounds with another sugar donor -nitrophenyl-β-d-glucopyranoside (NPGlc) was investigated. Results revealed that the same five steroids could be glucosylated to generate mono-glucosides and biosides by OcUGT1 through transglucosylation reactions. These data indicated that OcUGT1-assisted glycodiversification of steroids could be achieved through glucosylation and transglucosylation reactions. These results provide a way to diversify steroidal glycosides, which lays the foundation for the increase of the probability of obtaining active lead compounds.
Topics: Glucosides; Glycosides; Glycosylation; Glycosyltransferases; Ornithogalum; Steroids
PubMed: 31979165
DOI: 10.3390/molecules25030475 -
American Journal of Epidemiology Jan 2018Acrylamide may affect the sex hormone system in the prepubertal period. This study examined the cross-sectional associations between dietary acrylamide intake and sex...
Acrylamide may affect the sex hormone system in the prepubertal period. This study examined the cross-sectional associations between dietary acrylamide intake and sex hormone levels among preschool-age Japanese children. The study was conducted in 2006 among 230 boys and 198 girls aged 3-6 years in Aichi, Japan. Acrylamide intake was assessed using 3-day diet records. Urinary concentrations of estrone, estradiol, testosterone, and androst-5-ene-3β, 17β diol (hereafter referred to as androstenediol) were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry. Sex hormone levels were adjusted for urinary creatinine levels. The estimated acrylamide intake was 1.00 μg/kg of body weight per day. After controlling for age and other covariates, acrylamide intake was significantly positively associated with urinary levels of testosterone and androstenediol in boys. On average, boys in the highest quartile of acrylamide intake had 96.9% higher testosterone (95% confidence interval: -1.8, 295; P for trend = 0.048) and 34.5% higher androstenediol levels (95% confidence interval: -5.9, 92.3; P for trend = 0.04) than boys in the lowest quartile. In girls, there were no significant associations between acrylamide intake and the hormones measured. Acrylamide intake may alter androgen metabolism in preschool-age boys. Because this is a first observation, our findings require confirmation in additional studies.
Topics: Acrylamide; Child; Child, Preschool; Cross-Sectional Studies; Diet; Eating; Female; Gonadal Steroid Hormones; Humans; Japan; Male; Sex Characteristics
PubMed: 29309517
DOI: 10.1093/aje/kwx197 -
Toxics Nov 2022This paper describes a methodology for simultaneous determination of 19 steroid hormones, viz. estrone, estradiol, estriol, testosterone, 5α-dihydrotestosterone,...
This paper describes a methodology for simultaneous determination of 19 steroid hormones, viz. estrone, estradiol, estriol, testosterone, 5α-dihydrotestosterone, androstenedione, androstenediol, dehydroepiandrosterone, progesterone, pregnenolone, 17α-OH-progesterone, 17α-OH-pregnenolone, cortisone, cortisol, 11-deoxycortisol, 11-deoxycorticosterone, 11-dehydrocorticosterone, aldosterone, and corticosterone, in 500-µL of urine or serum/plasma. The method was optimized using isotopically labeled internal standards and liquid-liquid extraction followed by detection using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS). Dansylation of estrogens significantly improved their sensitivities (~11- to 23-fold) and chromatographic separation. The respective limit of detection (LOD) and limit of quantification (LOQ) of all analytes were 0.04−0.28 and 0.14−0.92 ng/mL in human urine, and 0.11−0.35 and 0.38−1.18 ng/mL in human serum/plasma. Recoveries of all analytes (except for progesterone) fortified at 10, 20, and 200 ng/mL in urine and serum were 80−120%, with standard deviations ranging from 0 to 17.3%. Repeated analysis of similarly fortified urine and serum samples yielded intra-day and inter-day variations of 0−21.7% and 0.16−11.5%, respectively. All analytes except cortisone exhibited weak matrix effects in urine and serum (−13.9−18.2%). The method was further validated through the analysis of the National Institute of Standards and Technology (NIST) plasma Standard Reference Material (SRM1950) with certified concentrations for cortisol, progesterone, and testosterone (coefficient of variation: 3−11%). The developed method was applied in the analysis of urine samples from 20 volunteers, which revealed the occurrence of 16 analytes with detection frequencies (DFs) > 80%. Furthermore, 15 analytes were found in plasma SRM1950, indicating the feasibility of our method in the analysis of steroid hormones in urine and serum/plasma. This method will facilitate analysis of steroid hormones in population-based biomonitoring studies.
PubMed: 36422894
DOI: 10.3390/toxics10110687 -
Diseases (Basel, Switzerland) Mar 2020Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males,...
Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis was conducted from autistic girls. Results show increased levels of several steroid hormones, especially in the class of androgens in autistic girls such as testosterone or androstenediol. The increase of the majority of steroid hormones in autistic girls is probably best explained multifactorially by a higher substrate provision in line with the previously developed cholesterol hypothesis of autism.
PubMed: 32183287
DOI: 10.3390/diseases8010006 -
Journal of Periodontology Oct 2015Sex hormones are linked to inflammation and bone turnover. The goal of this study is to explore the association between sex hormone levels and periodontitis in men using...
BACKGROUND
Sex hormones are linked to inflammation and bone turnover. The goal of this study is to explore the association between sex hormone levels and periodontitis in men using data from the third National Health and Nutrition Examination Survey (NHANES III).
METHODS
Data from 755 men (aged ≥ 30 years), including serum levels of testosterone, estradiol, sex hormone binding globulin, and androstenediol glucuronide, were analyzed. Calculated bioavailable testosterone (CBT) and estradiol-to-testosterone ratio were calculated. Periodontitis was defined using the latest classification of extent and severity of periodontitis for NHANES data (≥ 2 interproximal sites with ≥ 3 mm attachment loss, ≥ 2 interproximal sites with probing depth [PD] ≥ 4 mm not on the same tooth, or one site with PD ≥ 5 mm). Sex hormones were evaluated as categorized and continuous variables. Correlations between the presence and severity of periodontitis and levels of sex hormones were determined and expressed as odds ratios (ORs).
RESULTS
When adjusted for confounding factors, high total testosterone (TT) and CBT levels correlated with both the prevalence (OR [95% confidence interval (CI)], 2.1 [1 to 4.5] and 3.9 [1 to 14.8], respectively) and severity (OR [95% CI], 2.1 [1 to 4.3] and 3.4 [1.2 to 9.8]) of periodontitis. When continuous variables were used, the ORs (95% CIs) for presence and severity of periodontitis were 1.4 (0.6 to 3.3) and 1.5 (0.6 to 3.6) for TT and 1.3 (0.9 to 1.9) and 1.3 (0.9 to 1.8) for CBT, respectively.
CONCLUSIONS
These findings are consistent with the existence of an association of periodontitis with sex hormone levels, especially testosterone, in men.
Topics: Adult; Alcohol Drinking; Androstenediol; Biological Availability; Diabetes Mellitus; Dihydrotestosterone; Estradiol; Ethnicity; Gonadal Steroid Hormones; Humans; Male; Middle Aged; Nutrition Surveys; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Sex Hormone-Binding Globulin; Smoking; Testosterone; Waist-Hip Ratio
PubMed: 26062840
DOI: 10.1902/jop.2015.140530 -
International Journal of Molecular... Jun 2017In recent times, cytokines and hematopoietic growth factors have been at the center of attention for many researchers trying to establish pharmacological therapeutic... (Review)
Review
In recent times, cytokines and hematopoietic growth factors have been at the center of attention for many researchers trying to establish pharmacological therapeutic procedures for the treatment of radiation accident victims. Two granulocyte colony-stimulating factor-based radiation countermeasures have been approved for the treatment of the hematopoietic acute radiation syndrome. However, at the same time, many different substances with varying effects have been tested in animal studies as potential radioprotectors and mitigators of radiation damage. A wide spectrum of these substances has been studied, comprising various immunomodulators, prostaglandins, inhibitors of prostaglandin synthesis, agonists of adenosine cell receptors, herbal extracts, flavonoids, vitamins, and others. These agents are often effective, relatively non-toxic, and cheap. This review summarizes the results of animal experiments, which show the potential for some of these untraditional or new radiation countermeasures to become a part of therapeutic procedures applicable in patients with the acute radiation syndrome. The authors consider β-glucan, 5-AED (5-androstenediol), meloxicam, γ-tocotrienol, genistein, IB-MECA (⁶-(3-iodobezyl)adenosine-5'--methyluronamide), Ex-RAD (4-carboxystyryl-4-chlorobenzylsulfone), and entolimod the most promising agents, with regards to their contingent use in clinical practice.
Topics: Acute Radiation Syndrome; Animals; Cytokines; Hematopoietic System; Humans; Radiation-Protective Agents
PubMed: 28657605
DOI: 10.3390/ijms18071385 -
PloS One 2021Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands...
Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERβ include 5α-androstane-3β, 17β-diol (3βAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3βAdiol and Δ5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17β-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3βAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3βAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3βAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3βAdiol and E2 levels, not by Δ5-diol level.
Topics: Adult; Androstenediol; Chromatography, Liquid; Dehydroepiandrosterone; Estradiol; Female; Humans; Male; Menstrual Cycle; Sex Characteristics; Tandem Mass Spectrometry; Young Adult
PubMed: 34910781
DOI: 10.1371/journal.pone.0261440 -
Environment International Apr 2018Glycol ethers (GEs) are oxygenated solvents widely found in occupational and consumer water-based products. Some of them are well-known reproductive and developmental...
BACKGROUND
Glycol ethers (GEs) are oxygenated solvents widely found in occupational and consumer water-based products. Some of them are well-known reproductive and developmental toxicants.
OBJECTIVES
To study the variations in circulating sex steroid hormones, measured in cord blood, according to biomarkers of prenatal GE exposure.
METHODS
The study population comes from the PELAGIE mother-child cohort, which enrolled pregnant women from Brittany (France, 2002-2006). Maternal urine samples were collected from a random subcohort (n = 338) before 19 weeks' gestation, from which we measured 8 alkoxycarboxylic metabolites of GEs. We subsequently measured 13 sex steroid hormones and sex hormone-binding globulin (SHBG) in cord blood samples. Linear regressions adjusted for potential confounders were used, and nonlinear dose-response associations were investigated.
RESULTS
The detection rates of GE metabolites ranged from 4% to 98%; only the 5 most detected (>20%) metabolites were investigated further. Phenoxyacetic acid (detection rate > 95%) was associated with lower levels of SHBG and various steroids (17-alpha-hydroxy-Pregnenolone, delta-5-androstenediol, and dehydroepiandrosterone) among boys and higher SHBG and 16-alpha-hydroxy-dehydroepiandrosterone levels among girls. The two other highly detected metabolites, methoxyetoxyacetic acid and butoxyacetic acid, were associated with variations in estradiol. Butoxyacetic acid was associated with higher delta-5-androstenediol levels while detectable levels of methoxyacetic acid were associated with lower levels of this hormone.
CONCLUSION
Our study suggests that prenatal exposure to GE may affect endocrine response patterns, estimated by determining blood levels of sex steroid hormones in newborns. These results raise questions about the potential role of these changes in the pathways between prenatal GE exposure and previously reported adverse developmental outcomes, including impaired neurocognitive performance.
Topics: Female; Glycols; Gonadal Steroid Hormones; Humans; Infant, Newborn; Male; Maternal Exposure; Pregnancy
PubMed: 29421409
DOI: 10.1016/j.envint.2018.01.013