Dehydroepiandrosterone Research Articles

Hypothalamic-Pituitary-Adrenal Axis Activity and Metabolic Disorders in Kidney Transplant Recipients on Long-Term Glucocorticoid Therapy

Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24–102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68–0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.

Altered Steroidome in Women with Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ5 androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.

Modification of B-Nor Steroids Mediated by Filamentous Fungus Fusarium culmorum: Focus on 15α-Hydroxylase Activity

The metabolic activities of microorganisms to modify the chemical structures of organic compounds are an effective tool for the production of high-value steroidal drugs or active pharmaceutical ingredients (APIs). The integration of biotransformation into the synthesis of APIs can greatly reduce the number of reaction steps and achieve higher process efficiency, thus enabling their greener production. The current research efforts are focused on either the optimization of existing processes or identification of new potentially useful bioconversions. This study aimed to assess the catalytic abilities of the filamentous fungus Fusarium culmorum AM 282 to transform B-nor analogues (5(6→7)abeo compounds) of steroid hormones: androstenedione (AD), dehydroepiandrosterone (DHEA) and its acetate. Our previous studies have demonstrated that this strain is an active hydroxylating catalyst for many steroidal compounds with diverse structures. The results presented in this work showed that the hydroxylation of B-nor steroids occurred with the regio- and stereoselectivity typical of this strain in relation to the corresponding natural hormones of the standard 6:6 A/B series. After the transformations of B-nor-DHEA and its acetate, 15α-hydroxy-B-nor-DHEA was obtained as the sole product of the reaction, while the transformation of the AD analogue resulted in a mixture of its 15α- and 6α-hydroxy derivatives. A detailed analysis of the transformation course indicated that all the obtained hydroxy derivatives could be the result of the activity of the same enzyme. The presented results may provide a basis for research aimed at understanding the molecular nature of cytochrome P-450 monooxygenase from F. culmorum AM 282 with its ability for 15α-hydroxylation of steroidal compounds. An analysis of the pharmacokinetic and pharmacodynamic properties of the obtained metabolites with cheminformatics tools suggests their potential biological activity.

The effect of rapamycin treatment on mouse ovarian follicle development in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model.

Polycystic ovary syndrome (PCOS) is a complex reproductive and endocrine disorder affecting 5-10% of women of reproductive age, but the pathophysiology of PCOS still remains unknown. Here, the aim of our study was to analyze the effects of rapamycin treatment that may regulate impaired hormonal levels and folliculogenesis in dehydroepiandrosterone (DHEA)-treated PCOS mouse. We hypothesized that rapamycin may ameliorate the negative effects of PCOS in DHEA-induced PCOS mouse model. The target of rapamycin (TOR) gene product is a serine/threonine kinase that has been implicated in the control of cell growth, proliferation and autophagy, and rapamycin is a potent inhibitor of mTORC1 pathway. In this study, for the first time, mTORC1 and activation products are presented at protein and mRNA levels after rapamycin treatment in DHEA-induced PCOS mouse ovary. We showed that rapamycin treatment may regulate follicular development, hormonal levels and provide ovulation in DHEA-induced PCOS mouse. Additionally, we assessed decreased primordial follicle reserve, increased number of primary and secondary follicles, corpus luteum structure forms again after 10 days of rapamycin treatment. This study presented here suggests rapamycin treatment regulates hormonal phenotype and folliculogenesis in the ovary and also mTOR signalling pathway in granulosa cells of DHEA-induced PCOS mouse ovary which may have potential to attenuate understanding the mechanism of dominant follicle selection and anovulatory infertility.

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.MethodsTo investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).ResultsOur analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.ConclusionsOur comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Neurosteroids Alter p-ERK Levels and Tau Distribution, Restraining the Effects of High Extracellular Calcium

Neurosteroids are undeniably regarded as neuroprotective mediators, regulating brain function by rapid non-genomic actions involving interference with microtubules. Conversely, hyperphosphorylated Tau is considered responsible for the onset of a plethora of neurodegenerative diseases, as it dissociates from microtubules, leading to their destabilization, thus impairing synaptic vesicle transport and neurotransmission. Consequently, we aimed to investigate the effects of neurosteroids, specifically allopregnanolone (Allo) and dehydroepiandrosterone (DHEA), on the levels of total and phosphorylated at Serine 404 Tau (p-Tau) in C57BL/6 mice brain slices. In total tissue extracts, we found that neurosteroids elevated both total and p-Tau levels without significantly altering the p-Tau/Tau ratio. In addition, the levels of several enzymes implicated in Tau phosphorylation did not display significant differences between conditions, suggesting that neurosteroids influence Tau distribution rather than its phosphorylation. Hence, we subsequently examined the mitochondria-enriched subcellular fraction where, again, both p-Tau and total Tau levels were increased in the presence of neurosteroids. These effects seem actin-dependent, as disrupting actin polymerization by cytochalasin B preserved Tau levels. Furthermore, co-incubation with high [Ca2+] and neurosteroids mitigated the effects of Ca2+ overload, pointing to cytoskeletal remodeling as a potential mechanism underlying neurosteroid-induced neuroprotection.

Effect of Endogenous Hormone Levels on Basal Metabolic Rate in Men With Obesity.

Basal metabolic rate (BMR) is an important factor in weight management and is influenced by fat-free mass (FFM), fat mass (FM) and age. Current knowledge of the influence of hormonal levels on BMR is based on studies with small populations, studies that investigate exogenous administration and studies frequently lacking correction for body composition. Cross-sectional study. All men (n = 457) who were referred to our centre for a metabolic work-up were eligible for inclusion. Median age was 47 (18-78) years and the vast majority had obesity (BMI ≥ 30 kg/m², 90.9%). All men had a measurement of BMR, body composition and measurement of testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH) and free thyroxine (fT4). Men with low, normal and/or high levels of each of these hormones were compared. The association between hormone levels and BMR was assessed through linear regression models. All analyses were controlled for FFM, FM and age. In men with obesity, testosterone (total or free) was not associated with BMR. Linear regression analysis showed that DHEAS was positively associated with BMR in a sample of men with obesity and normal endogenous DHEAS levels, with the following equation: BMR (adjusted R² = 0.72): (BMR [kcal/d] = 513.402 + 18.940 × FFM [kg] + 9.507 × FM [kg] - 3.362 × age [years] + 0.307 × DHEAS [µg/dL]) (p < 0.01). TSH, fT4 and IGF-1 were not associated with BMR. In men with obesity, endogenous DHEAS is positively associated with BMR. Testosterone, TSH, fT4 and IGF-1 were not associated with BMR in men with obesity. Since we examined the specific population of men with obesity and only examined endogenous hormone levels, no extrapolation of results to other populations or the overall population can be made.

Maternal Obesity and Differences in Child Urine Metabolome

Background/objective: Approximately one-third of pregnant individuals in the U.S. are affected by obesity, which can adversely impact the in utero environment and offspring. This study aimed to investigate the differences in urine metabolomics between children exposed and unexposed to maternal obesity. Methods: In a study nested within a larger pregnancy cohort of women–offspring pairs, we measured untargeted metabolomics using liquid chromatography–mass spectrometry in urine samples from 68 children at 4–8 years of age. We compared metabolite levels between offspring exposed to maternal obesity (body mass index [BMI] ≥ 30.0 kg/m2) vs. unexposed (maternal BMI 18.5–24.9 kg/m2) and matched them on covariates, using two-sample t-tests, with additional sensitivity analyses based on children’s BMI. This study reports statistically significant results (p ≤ 0.05) and potentially noteworthy findings (fold change &gt; 1 or 0.05 &lt; p &lt; 0.15), considering compounds’ involvement in common pathways or similar biochemical families. Results: The mean (SD) maternal age at study enrollment was 28.0 (6.3) years, the mean child age was 6.6 (0.8) years, 56% of children were male, and 38% of children had a BMI in the overweight/obese range (BMI ≥ 85th percentile). Children exposed to maternal obesity had lower levels of 5-hydroxyindole sulfate and 7-hydroxyindole sulfate and higher levels of secondary bile acids. Phenylacetic acid derivatives were lower in offspring exposed to obesity and in offspring who had a current BMI in the overweight/obese range. Exposure to maternal obesity was associated with lower levels of androgenic steroid dehydroepiandrosterone sulfate (DHEA-S). Conclusions: In this preliminary study, children exposed to maternal obesity in utero had differences in microbiome-related metabolites in urine suggestive of altered microbial catabolism of tryptophan and acetylated peptides. Some of these differences were partially attributable to the offspring’s current BMI status. This study highlights the potential of urine metabolomics to identify biomarkers and pathways impacted by in utero exposure to maternal obesity.

Effects of Lupeol on Estrogen and Androgen Receptor-Positive Breast and Prostate Cancer Cells

Background: Different reports have shown that prostate and breast cancers are the most common cancers worldwide. Lupeol, a dietary triterpene, provides various beneficial effects including anti-cancer properties. The current study aims to investigate the anti-proliferative and antioxidant effects of lupeol, in line with the effects of lupeol on the expression of estrogen and androgen receptors in breast (MCF-7) and prostate (LNCaP) cancer cell lines. Methods: MCF-7 and LNCaP cells were incubated with increasing concentrations of the lupeol (1, 10, and 100 µM) for 24h. The cytotoxicity of the lupeol was assessed by MTT and Neutral Red assays. Moreover, TAC (total antioxidant capacity), and gene expression of androgen and estrogen receptors were measured by spectrophotometric and qPCR methods, respectively. Overall, 17 beta-estradiol (E2) (9 nM) and dehydroepiandrosterone (DHEA) (5 µM) were selected as positive controls. Results: The highest concentration of the lupeol induced cytotoxic effects on MCF-7 and LNCaP cells. Various levels of lupeol at specified time intervals increased TAC levels in comparison with the control group. Moreover, the expression levels of estrogen receptors (α and β) and androgen receptors were negatively affected by lupeol. Conclusion: The findings of our study indicate that lupeol could serve as a promising, and accessible multi-functional anti-tumor agent against hormone-positive breast and prostate cancers.

Enhancing Sleep and Reducing Occupational Stress Through Forest Therapy: A Comparative Study Across Job Groups.

The coronavirus disease-2019 (COVID-19) pandemic radically shifted occupational patterns, leading to increased telecommuting and related stressors. Healthcare providers, among the most impacted group, faced heightened risks and workplace changes. Our study examined the efficacy of forest therapy in alleviating work-induced stress across various professions, exploring the need for profession-specific stress-relief strategies in the post-pandemic workplace. To examine the impact of COVID-19 on professionals, 62 participants were recruited, consisting of 20 healthcare providers, 21 information technology (IT) specialists, and 21 teachers. Instruments such as Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale, along with salivary tests for cortisol and melatonin, were used to assess the participants' sleep and stress levels. A specialized forest healing program was implemented among these participants. Data analysis was conducted using SPSS Win Ver. 22.0, utilizing paired t-tests and a repeated measures analysis of variance. Significant improvements were observed in the participants' sleep metrics, depression scales, and stress levels after the forest healing program. Physiological measures indicated an increase in melatonin and a decline in cortisol and dehydroepiandrosterone sulfate levels, with only cortisol changes being statistically significant. Teachers, participating during school vacations, exhibited minimal stress-related physiological changes. Overall, the program demonstrated widespread health benefits regardless of occupation or gender. This study showed that forest therapy reduced stress equally across professions, including healthcare providers, IT specialists, and teachers. Individual physiological responses may play a greater role in stress relief than the specific occupation.

Healthy plasma lipidomic signatures depend on sex, age, body mass index, and contraceptives but not perceived stress.

Perceived stress is thought to contribute to the pathogenesis of metabolic, vascular, mental, and immune diseases, with different susceptibilities in women and men. The present study investigated if and how perceived stress and/or demographic variables including sex, age, body mass index, regular prescription drugs, occasional analgesics, or dietary supplements manifested in plasma lipidomic profiles, obtained by targeted and untargeted mass spectrometry analyses. The study included 217 healthy women and 108 healthy men, aged 18-68 years, who were recruited in a 2:1 female:male ratio to account for women with/without contraceptives. As expected, dehydroepiandrosterone sulfate (DHEAS) and ceramides were higher in men than women, and DHEAS decreased with age, while ceramides increased. Contrary to expectations, neither DHEAS nor ceramides were associated with perceived stress (PSQ30 questionnaire), which was however, associated with BMI in men, but not in women. None of the lipid species or classes showed a similar "age X sex X BMI" interaction, but the endocannabinoid palmitoylethanolamide (PEA) correlated with BMI and hypertension. Independent of perceived stress, lysophosphatidylcholines (LPCs) were lower in women than men, whereas LPC metabolites, lysophosphatidic acids (LPAs), were higher in women. The LPA:LPC ratio was particularly high in women using oral contraceptives suggesting a strong hormone-induced extracellular conversion of LPCs to LPAs, which is catalyzed by the phospholipase D, autotaxin. The results reveal complex sex differences in perceived stress and lipidomic profiles, the latter being exacerbated by contraceptive use, but perceived stress and lipids were not directly correlated.

Serotonin, cortisol, and DHEA-S levels in anxious and depressive pregnant women living with HIV

Pregnancy in women living with human immunodeficiency virus (WLWH) represents an important challenge for maternal-fetal health. Besides, they can also present anxiety (Anx) and depression (Dep). Imbalances in serotonin (5-HT), dehydroepiandrosterone sulfate (DHEA-S), and cortisol (CORT) levels can contribute to Anx and Dep manifestations. Currently, there is not enough data about the neuroendocrine and neurochemical changes in pregnant WLWH with affective disorders. This study aimed to characterize 5-HT, DHEA-S, and CORT plasma levels in Mexican pregnant WLWH presenting Anx/Dep. Forty-two adult pregnant women were recruited during the third trimester of gestation at the National Institute of Perinatology in Mexico during 2019–2022. These patients were divided into three groups: (1) pregnant WLWH with Anx/Dep (n = 16), (2) pregnant without HIV but with Anx/Dep (n = 12), and (3) healthy pregnant women without Anx/Dep (n = 14). WLWH presented a marked reduction in 5-HT (41.33 ± 39.37 ng/dL) compared to non-infected pregnant women with Anx/Dep (220.2 ± 151.8 ng/dL) and the healthy group (370.0 ± 145.3 ng/dL). Anx/Dep infected and uninfected pregnant women showed a significant reduction in DHEA-S levels (86.58 ± 30.59 and 76.9 ± 36.7 µg/dL, respectively) compared to healthy subjects (149.7 ± 44.6 µg/dL). Anx and Dep symptoms were inversely correlated with 5-HT and DHEA-S levels. No significant differences were observed in CORT levels among the three groups (p = 0.094). Our results suggest the presence of a disbalance in 5-HT and DHEA-S levels in pregnant WLWH with affective symptoms.

Implantable Fluorogenic DNA Biosensor for Stress Detection.

Implantable sensors that can monitor analytes related to cognitive and physiological status have gained significant focus in recent years. We have developed an implantable biosensor to detect dehydroepiandrosterone sulfate (DHEA-S), a biomarker related to stress. The biosensor strategy was based on the principle of forced intercalation (FIT) aptamers designed to detect subtle intramolecular changes during aptamer-target binding events. By incorporating a steroid-specific fluorogenic aptamer into a hydrogel, the sensitivity and biostability of the FIT biosensor fiber were improved, which were essential for designing implantable sensors to monitor biomarker levels in the living body. The polyethylenimine-based hydrogel chosen for this study produced an optically transparent cross-linked network with optimal microstructure, physicochemical, and mechanical properties, making it suitable for optical biosensors. The in vitro studies showed that the biosensor fiber was successfully activated in human serum and skin analogue, providing a linear response to physiological concentrations of the steroid. We believe that this type of implantable platform can be effective in monitoring more complex biomarkers associated with physiological or psychological health.

Rat Model of Menopausal/Andropausal Hypertension with Different Sensitivities to Non-Genomic Antihypertensive Responses of Female and Male Sex Steroids.

Hypertension is prevalent in older women and men, but the impact of sex differences is unclear. Blood pressure (BP) was evaluated weekly for 15 weeks using tail-cuff plethysmography in intact or gonadectomized female and male rats. Similarly, gonadectomized rats were subcutaneously treated daily for 15 weeks with estradiol in females or testosterone in males. Treatment with estrogen in males and androgen in females for BP was also examined. The non-genomic antihypertensive potency and efficacy of different sex steroids were determined; catheters were implanted in the carotid artery of hypertensive rats for BP recording with bolus injections in the jugular vein at cumulative doses (1 × 10-7-1 × 10-4<sc>M</sc> kg-1 min-1) of dehydroepiandrosterone (DHEA), estradiol, testosterone, or 5β-dihydrotestosterone (5β-DHT). Data showed a time-dependent increase in BP after gonadectomy in female and male rats until hypertension values were reached. Males are more sensitive to the development of hypertension than females. The increases in BP in females and males were completely prevented by estradiol or testosterone, respectively. Testosterone completely prevented hypertension in females, whereas estradiol only partially in males. Antihypertensive potencies in conscious hypertensive rats were DHEA = 5β-DHT = testosterone >> estradiol, in females and DHEA = 5β-DHT >> testosterone >> estradiol in males. The efficacy was DHEA = 5β-DHT = testosterone >> estradiol in females and 5β-DHT = DHEA >> testosterone >> estradiol in males. Gonadectomized males developed hypertension faster than females, suggesting that androgen deficiency plays an important role in BP reduction. Antihypertensive responses of steroids are structure-dependent; estradiol demonstrated the lowest potency, whereas 5β-DHT was a potent antihypertensive without estrogenic and androgenic actions, suggesting it is as a therapeutic candidate for controlling hypertension in both sexes.

The state of the hypothalamic-pituitary-adrenal system in workers exposed to electric and magnetic fields of industrial frequenc

Introduction. Electric and magnetic fields of industrial frequency are an integral part of production processes, and their effect on the human body is of increasing interest both among scientists and among specialists in the field of medicine and occupational safety. In recent decades, there has been growing concern about the potential impact of these areas on the health of workers, especially those who are exposed to prolonged exposure in the course of their professional activities. In this context, we pay special attention to the neuroendocrine system, which plays a key role in regulating many physiological processes, including metabolism, stress reactions and maintaining homeostasis. The study of the fundamentals of the neuroendocrine system and the mechanisms of the effect of electromagnetic fields on the body not only contributes to the deepening of scientific knowledge in the field of biomedical research, but also has practical significance in ensuring occupational safety and improving working conditions in industrial enterprises, allowing to identify possible health consequences and develop effective measures to protect workers from negative bioeffects. The study aims to research the effects of electric and magnetic fields of industrial frequency on the functional state of the hypothalamic-pituitary-adrenal system of employees of electric grid facilities. Materials and methods. Specialists examined 144 employees of the main group engaged in the repair and operation of electric grid facilities and 40 employees of the control group who were not exposed to electromagnetic fields of industrial frequency. We determined the concentration of adrenocorticotropic hormone, cortisol and dehydroepiandrosterone sulfate in blood serum samples and calculated the ratio of dehydroepiandrosterone sulfate to cortisol. Results. Workers exposed to the combined effects of electric and magnetic fields of industrial frequency had a lower (p&lt;0.05) level of adrenocorticotropic hormone (1.9 [0.5; 3.9] pg/ml) and dehydroepiandrosterone sulfate (5.8 [3.7; 8.4] mmol/l) in the blood compared with the group of workers exposed to magnetic fields industrial frequency fields (4.4 [2.1; 12.9] pg/ml; 9.8 [6.3; 14.5] mmol/l) and to the control group (6.4 [4.0; 19.8] pg/ml; 7.8 [4.7; 13.3] mmol/l), respectively. The scientists also revealed in the group of workers exposed to combined exposure in the field, the association of a low ratio of dehydroepiandrosterone sulfate and cortisol with the development of cardiovascular diseases and feedback from work experience (p&lt;0.05). Limitations. The study is limited by the number of people surveyed (144 employees). Conclusion. The results of the study indicate the hypoactivity of the hypothalamic-pituitary-adrenal system induced by exposure to electric and magnetic fields of industrial frequency, manifested by a decrease in the level of adrenocorticotropic hormone, dehydroepiandrosterone sulfate and its relationship to cortisol in workers exposed to combined effects of electric and magnetic fields of industrial frequency. Ethics. The work complies with ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting Scientific medical research with human participation" as amended in 2000 and the "Rules of Clinical Practice in the Russian Federation" approved by Order of the Ministry of Health of the Russian Federation dated 04/01/2016 No. 200n. We received informed consent from each examined person to participate in the study, approved in accordance with the established procedure by the local Ethics Committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics Committee No. 17 dated 12/16/2015).

Pre-Conception Androgen Levels and Obstetric Outcomes in Polycystic Ovary Syndrome: A Single-Center Retrospective Study

Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. Methods: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. Results: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. Conclusions: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-β-HSD (17β-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients.

Hormonal status in women with respiratory viral infections during critical periods

Pregnancy and menopause are critical periods in a woman’s life. Due to physiological changes in the neuroendocrine system regulation, susceptibility to respiratory viral infections increases in these periods, while affecting all organs and systems of the human body. The aim of this review was to analyze the literature data on the effect of acute respiratory viral infections on neuroendocrine regulation in women during pregnancy and menopause. We reviewed full-text publications in the public domain from the PubMed, eLibrary.ru, and Google Scholar databases with a coverage period of more than twenty years (2000–2023). Disruptions of the progesterone and estrogen production during infection with the influenza A (H1N1) and influenza B viruses have been shown in experimental studies. Hormonal status changes in pregnant women are detected during infection with the influenza A virus (H3N2) and depend on antiviral antibody titers and the presence of fetoplacental insufficiency. Pregnant women with COVID-19 may experience changes in the brain structure activities, as indicated by a high frequency of those in olfactory sensitivity and psychoemotional disorders. During menopause, infection with the SARS-CoV-2 virus leads to changes in the production of thyroxine, prolactin, estradiol, testosterone, cortisol, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate.

Meconium as an Analyte for Androgen Exposure: Analysis Through Varying Maternal-Fetal Biomarkers.

Meconium, the first stool produced by neonates, has been used as an analyte for exogenous fetal exposures. However, few studies have investigated the relationship between meconium and androgen exposure in utero. Here, we examine the associations of testosterone and dehydroepiandrosterone (DHEA) across maternal antenatal salivary testosterone, cord blood, meconium, and infant salivary testosterone. A total of 47 women with singleton, uncomplicated pregnancies, and their infants were included in this study. Participants were recruited from an academic obstetric clinic. Maternal saliva was collected at 36-weeks' gestation. Cord blood and meconium were collected at birth. Infant salivary testosterone was collected at 1 and 4 weeks of age. Multivariate model results showed that meconium testosterone was associated with neonatal testosterone at 1 (F=5.62, p=0.029) and 4 weeks (F=4.28, p=0.048) postnatal age; no sex differences were detected. This study suggests meconium is a valuable tool for evaluating endogenous androgen exposure and should be used in future studies to investigate the fetal hormonal milieu.

Bioorthogonal Regulated Metabolic Balance for Promotion of Ferroptosis and Mild Photothermal Therapy.

The nanozyme with NADPH oxidase (NOX)-like activity can promote the consumption of NADPH and the generation of free radicals. In consideration of that the upregulation of glucose-6-phosphate dehydrogenase (G6PD) would accelerate the compensation production of NADPH, for inhibition of G6PD activity, our designed bioorthogonal nanozyme can in situ catalyze pro-DHEA to produce G6PD inhibitor and dehydroepiandrosterone (DHEA) drugs to inhibit G6PD activity. Therefore, the well-defined platform can disrupt NADPH homeostasis, leading to the collapse of the antioxidant defense system in the tumor cells. The enzyme-like activity of PdCuFe is further enhanced when irradiated by NIR-II light. The destruction of NADPH homeostasis can promote ferroptosis and, in turn, facilitate mild photothermal therapy. Our design can realize NADPH depletion and greatly improve the therapeutic effect through metabolic regulation, which may provide inspiration for the design of bioorthogonal catalysis.

Screening of the most common cardiometabolic diseases based on risk factor assessment among military personnel

Objective — to assess the prevalence of major cardiometabolic diseases by identifying their risk factors and comparing them with metabolic disorders and stress indicators in military personnel. Materials and methods. The study included 74 male military personnel with an average age of 43.4 [31.4; 50.6] years. Among all the participants, the proportion of individuals with hypertension (HTN) was 51.4%, with dyslipidemia (DLP) — 75.7%, with metabolic­associated steatotic liver disease (MASLD) — 48.6%, and with overweight or obesity — 51.4%. The participants were divided into groups based on the number of cardiometabolic diseases: group 1 (comparison) consisted of military personnel without HTN, DLP, or MASLD (n=14, 18.9%), group 2 — personnel with 1—2 of the above­mentioned cardiometabolic diseases (n=32, 43.2%), and group 3 — military personnel with comorbid pathology, including HTN, DLP, and MASLD (n=28, 37.8%). All participants were assessed for anthropometric profile, traditional clinical and biochemical indicators. Stress indicators included dehydroepiandrosterone sulfate (DHEA­S), cortisol, and oxidative stress marker 8­OH­deoxyguanosine (8­OH­DG), which were measured in the blood using immunoassay methods. Results. Among military personnel with HTN, overweight/obesity was twice as common (p=0.003, χ2=9.110), MASLD was 3.3 times more frequent (p=0.0001, χ2=19.598), and DLP was 1.7 times more frequent (p=0.0001, χ2=15.418). Among military personnel with MASLD, overweight/obesity was observed three times more frequently (p=0.0001, χ2=19.598), and dyslipidemia was 1.6 times more common (p=0.0001, χ2=13.416). Personnel with more cardiometabolic diseases were significantly older (p=0.003). In group 3, 21.4% had a normal BMI, while in group 1, 28.6% were overweight or had obesity (p=0.001). The increase in the number of cardiometabolic diseases between groups was accompanied by a significant reduction in skeletal muscle percentage (p=0.039 for group 1 vs group 2; p=0.001 for group 1 vs group 3; p=0.001 for group 2 vs group 3). Military personnel in group 3 had significantly higher BMI, waist circumference (WC), total fat percentage, and lower skeletal muscle percentage compared to groups 1 and 2 (p=0.001 for all comparisons). The highest levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid (UA), and the lowest AST/ALT ratio were observed in group 3 compared to group 1 (p=0.002; p=0.0001; p=0.001; p=0.0001) and group 2 (p=0.0001; p=0.0001; p=0.0001; p=0.0001), respectively. Alkaline phosphatase levels were significantly lower in group 3 compared to group 1 (p=0.048). Lipid profile deterioration was observed with an increase in the number of cardiometabolic diseases: total cholesterol (TC), triglycerides (TG), very low­density lipoprotein cholesterol (VLDL­C), and low­density lipoprotein cholesterol (LDL­C) levels were significantly higher in group 3 compared to group 1 (p=0.0001; p=0.0001; p=0.0001; p=0.007) and group 2 (p=0.0001; p=0.024; p=0.002; p=0.005), respectively. In group 2, only TG (p=0.0001) and VLDL­C (p=0.0001) levels were higher compared to group 1. DHEA­S levels were significantly lower in group 3 compared to group 1 (p=0.019), but no differences in cortisol levels were found. 8­OH­DG levels were significantly lower in groups 2 (p=0.003) and 3 (p=0.019) compared to group 1. Correlation analysis revealed that stress hormone levels were inversely associated with WC (p=0.016), AST (p=0.004), ALT (p=0.021), total bilirubin (p=0.033), UA (p=0.002), glycated haemoglobin (HbA1с) (p=0.024), TC (p=0.002), TG (p=0.001), and VLDL­C (p=0.001). Conclusions. Cardiometabolic diseases are highly prevalent among military personnel, and comorbidity is a frequent phenomenon that contributes to a significant increase in cardiovascular risk and highlights the need for optimized preventive and therapeutic strategies. The increase in the number of cardiometabolic diseases is associated with older age, worsened anthropometric status, liver function tests, increased uric acid levels, and deteriorating lipid profile. DHEA­S can be considered a marker of chronic stress in individuals with cardiometabolic comorbidity. Monitoring and timely correction of WC, AST, ALT, total bilirubin, UA, HbA1с, TC, TG, and VLDL­C levels among military personnel are necessary, as these indicators are related to stress and can improve cardiometabolic disease prevention.