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European Child & Adolescent Psychiatry Aug 2023Although the link between androgens and depression is well established in adults, the effects of cofactors on this association are less clearly understood, particularly... (Observational Study)
Observational Study
Although the link between androgens and depression is well established in adults, the effects of cofactors on this association are less clearly understood, particularly in youth. Epidemiological cohort study of adolescents in Dresden, Germany. Analyses comprised data of 985 individuals assessed at baseline and of 512 individuals at 1-year follow-up. We investigated multivariable regression models for cross-sectional and longitudinal associations of hair testosterone, dehydroepiandrosterone (DHEA), and their cortisol ratios with 12-month diagnoses of major depressive disorder (MDD) and MDD without any anxiety disorder assessed with standardized diagnostic interview (DIA-X-5), and with dimensional depression scores (PHQ-9, PROMIS), separately for males and females. The potential moderating effect of social support was determined. Cross-sectional analyses yielded inverse associations of testosterone and DHEA with MDD and MDD without any anxiety disorders in males. In cross-sectional and longitudinal analyses, baseline ratio cortisol/DHEA was significantly, inversely associated to PROMIS-depression in males. Only cross-sectional associations for ratio cortisol/DHEA and PROMIS-depression remained significant after Bonferroni-Holm correction. No robust associations were observed in female participants. Social support exerted no consistent moderating effect on the investigated association. The present observational cohort study showed no consistent association of hair androgen concentrations with depressive disorders in adolescents. However, findings provide some support for the association between the cortisol/DHEA ratio and depression in males. Longitudinal research designs in large samples are needed to understand the interplay between androgens, depression, and developmental and social factors in youth.
Topics: Adult; Male; Humans; Adolescent; Female; Androgens; Dehydroepiandrosterone; Depressive Disorder, Major; Cohort Studies; Cross-Sectional Studies; Hydrocortisone; Testosterone; Hair
PubMed: 35112167
DOI: 10.1007/s00787-021-01929-w -
BMC Musculoskeletal Disorders Jun 2021Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of...
BACKGROUND
Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons.
METHODS
Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined.
RESULTS
In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group.
CONCLUSIONS
DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.
Topics: Animals; Cells, Cultured; Dehydroepiandrosterone; Diabetes Mellitus, Experimental; Glucose; Oxidative Stress; Rats; Rats, Sprague-Dawley; Tenocytes
PubMed: 34090401
DOI: 10.1186/s12891-021-04398-z -
Theriogenology Nov 2021Cortisol (C) and dehydroepiandrosterone (DHEA) are recognized as the main fetal steroids, and they are likely to influence fetal development and have long-term effects...
Cortisol (C) and dehydroepiandrosterone (DHEA) are recognized as the main fetal steroids, and they are likely to influence fetal development and have long-term effects on newborn hypothalamic-pituitary-adrenal axis (HPA) function. DHEA is often measured as its sulfates and expressed as DHEA-S. Hair analysis represents a promising methodological approach for the non-invasive measurement of steroids, allowing for a retrospective analysis of the total exposure to steroids over time, and avoiding the influence of acute events or circadian fluctuations. Hair cortisol and DHEA concentrations have been investigated in cows, but no studies have been performed on calves. The object of this study was to evaluate hair cortisol (HC) and hair DHEA-S (HDHEA-S) concentrations in beef calves from birth to six months of age. Hair samples of 12 beef calves (seven males, five females) were firstly collected at birth (T1) and then every three weeks up to six months of age (T2-T10), collecting only the re-grown hair. HC and HDHEA-S were analyzed by radioimmunoassay (RIA). Calves sex, weight and APGAR score were registered immediately after birth. Statistical analysis revealed that both HC and HDHEA-S were influenced by sampling time (P < 0.001). HC concentrations were higher at T1 compared to all subsequent samplings (T2-T10, P < 0.01); HC concentrations were higher at T2 compared to T4-T10 (P < 0.01), while no further changes were detected from T3 onward. Higher HDHEA-S concentrations were registered at T1, T2 and T3 compared to all the other samplings (P < 0.01). No correlation was found between hair concentrations of both steroids and calf sex or birthweight. APGAR score was negatively correlated only with HC at birth (P < 0.05). These data demonstrate that C and DHEA-S are quantifiable in the hair of calves and are influenced by their age. The higher HC detected at birth (T1) probably reflects the high serum C concentrations present late in pregnancy and increased by the fetal HPA axis, by which parturition is initiated in cows. The highest HDHEA-S at birth (T1) in calves indicates that the largest amounts of DHEA and its sulfates are produced during fetal development. Moreover, the findings of higher HC at three weeks after birth and of higher HDHEA-S until six weeks after birth, suggest that C and DHEA secretion continues also beyond birth, and that these steroids could be involved in the events occurring during the challenging first weeks of age in the calf.
Topics: Animals; Cattle; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Parturition; Pituitary-Adrenal System; Pregnancy; Retrospective Studies
PubMed: 34517287
DOI: 10.1016/j.theriogenology.2021.08.037 -
Journal of Neuroinflammation Oct 2018It is a well-known fact that DHEA declines on ageing and that it is linked to ageing-related neurodegeneration, which is characterised by gradual cognitive decline.... (Review)
Review
It is a well-known fact that DHEA declines on ageing and that it is linked to ageing-related neurodegeneration, which is characterised by gradual cognitive decline. Although DHEA is also associated with inflammation in the periphery, the link between DHEA and neuroinflammation in this context is less clear. This review drew from different bodies of literature to provide a more comprehensive picture of peripheral vs central endocrine shifts with advanced age-specifically in terms of DHEA. From this, we have formulated the hypothesis that DHEA decline is also linked to neuroinflammation and that increased localised availability of DHEA may have both therapeutic and preventative benefit to limit neurodegeneration. We provide a comprehensive discussion of literature on the potential for extragonadal DHEA synthesis by neuroglial cells and reflect on the feasibility of therapeutic manipulation of localised, central DHEA synthesis.
Topics: Aging; Animals; Dehydroepiandrosterone; Encephalitis; Humans; Neurodegenerative Diseases
PubMed: 30326923
DOI: 10.1186/s12974-018-1324-0 -
Cleveland Clinic Journal of Medicine Nov 2005Deficiency of dehydroepiandrosterone (DHEA) is associated with lupus erythematosus, diabetes mellitus, Alzheimer disease, and some cancers, but we are not yet ready to... (Review)
Review
Deficiency of dehydroepiandrosterone (DHEA) is associated with lupus erythematosus, diabetes mellitus, Alzheimer disease, and some cancers, but we are not yet ready to conclude that prescribing supplemental DHEA is helpful in these or any other conditions. DHEA shows some promise in observational clinical studies and laboratory experiments, but we still need large-scale human studies to answer key questions. For now, we do not have enough evidence to recommend routine treatment with DHEA. As with other supplements, quality control is always a concern, and different brands may contain different amounts of active ingredient.
Topics: Adjuvants, Immunologic; Dehydroepiandrosterone; Dietary Supplements; Humans; Neoplasms
PubMed: 16315437
DOI: 10.3949/ccjm.72.11.965 -
Cleveland Clinic Journal of Medicine Jan 2021
Topics: Androgens; Dehydroepiandrosterone; Female; Humans; Postmenopause; Testosterone
PubMed: 33384314
DOI: 10.3949/ccjm.88a.20195 -
American Journal of Physiology. Heart... Dec 2018Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone, which has the highest serum concentration among steroid hormones with DHEA sulfate (DHEAS). DHEA possesses...
Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone, which has the highest serum concentration among steroid hormones with DHEA sulfate (DHEAS). DHEA possesses an inhibitory action on glucose-6-phosphate dehydrogenase (G6PD), the first pentose-phosphate pathway enzyme that reduces NADP to NADPH. DHEA induced relaxation of high K-induced contraction in rat arterial strips, whereas DHEAS barely induced it. We studied the effects of DHEA on L-type Ca current ( I) of A7r5 arterial smooth muscle cells and compared the mechanism of inhibition with that produced by the 6-aminonicotinamide (6-AN) competitive inhibitor of G6PD. DHEA moderately inhibited I that was elicited from a holding potential (HP) of -80 mV [voltage-independent inhibition (VIDI)] and accelerated decay of I during the depolarization pulse [voltage-dependent inhibition (VDI)]. DHEA-induced VDI decreased peak I at depolarized HPs. By applying repetitive depolarization pulses from multiple HPs, novel HP-dependent steady-state inactivation curves ( f-HP) were constructed. DHEA shifted f-HP to the left and inhibited the window current, which was recorded at depolarized HPs and obtained as a product of current-voltage relationship and f-HP. The IC value of I inhibition was much higher than serum concentration. DHEA-induced VDI was downregulated by the dialysis of guanosine 5'- O-(2-thiodiphosphate), which shifted f-voltage to the right before the application of DHEA. 6-AN gradually and irreversibly inhibited I by VIDI, suggesting that the inhibition of G6PD is involved in DHEA-induced VIDI. In 6-AN-pretreated cells, DHEA induced additional inhibition by increasing VIDI and generating VDI. The inhibition of G6PD underlies DHEA-induced VIDI, and DHEA additionally induces VDI as described for Ca channel blockers. NEW & NOTEWORTHY Dehydroepiandrosterone, the most abundantly released adrenal steroid hormone with dehydroepiandrosterone sulfate, inhibited L-type Ca current and its window current in aortic smooth muscle cells. The IC value of inhibition decreased with the depolarization of holding potential to 15 µM at -20 mV. The inhibition occurred in a voltage-dependent manner as described for Ca channel blockers and in a voltage-independent manner because of the inhibition of glucose-6-phosphate dehydrogenase.
Topics: Action Potentials; Animals; Arteries; Calcium Channels, L-Type; Cells, Cultured; Dehydroepiandrosterone; Female; Hormones; Myocytes, Smooth Muscle; Rats; Rats, Wistar
PubMed: 30379558
DOI: 10.1152/ajpheart.00291.2018 -
Bioscience Trends Dec 2015Diminished ovarian reserve (DOR) has a high morbidity rate worldwide and has become a primary cause of infertility. DOR is a daunting obstacle in in vitro fertilization... (Review)
Review
Diminished ovarian reserve (DOR) has a high morbidity rate worldwide and has become a primary cause of infertility. DOR is a daunting obstacle in in vitro fertilization (IVF) and leads to poor ovarian response, high cancellation rates, poor IVF outcomes, and low pregnancy rates. Abnormal autoimmune function may also contribute to DOR. Dehydroepiandrosterone (DHEA) is a C19 androgenic steroid. DHEA is secreted mainly by the adrenal gland, and its secretion declines with age. DHEA has a pro-inflammatory immune function that opposes cortisol. The cortisol to DHEA ratio increases with age, which may lead to decreased immune function. DHEA supplementation helps improve this situation. A number of clinical case control studies and several prospective randomized clinical trials have observed a positive effect of DHEA supplementation in women with DOR. However, the underlying mechanism by which DHEA improves ovarian reserve remains unclear. DHEA functions as an immune regulator in many different tissues in mammals and may also play an important role in regulating the immune response in the ovaries. The conversion of DHEA to downstream sex steroids may allow it to regulate the immune response there. DHEA can also enhance the Th1 immune response and regulate the balance of the Th1/Th2 response. DHEA treatment can increase selective T lymphocyte infiltration in mice, resulting in a decline in the CD4+ T lymphocyte population and an upregulation of the CD8+ T lymphocyte population in ovarian tissue, thus regulating the balance of CD4+/CD8+ T cells. This review mainly focuses on how DHEA supplementation affects regulation of the immune response in the ovaries.
Topics: Dehydroepiandrosterone; Dietary Supplements; Female; Fertilization in Vitro; Humans; Immunity, Cellular; Ovarian Reserve; Ovary; Th1 Cells
PubMed: 26781792
DOI: 10.5582/bst.2015.01154 -
Proceedings of the National Academy of... Jul 2001
Review
Topics: Aging; Animals; Dehydroepiandrosterone Sulfate; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Receptors, Cytoplasmic and Nuclear; Transcription Factors
PubMed: 11459947
DOI: 10.1073/pnas.161278698 -
PloS One 2022To better understand how health risk processes are linked to adrenarche, measures of adrenarcheal timing and tempo are needed. Our objective was to describe and classify...
To better understand how health risk processes are linked to adrenarche, measures of adrenarcheal timing and tempo are needed. Our objective was to describe and classify adrenal trajectories, in terms of timing and tempo, in a population of children transitioning to adolescence with repeated measurements of salivary dehydroepiandrosterone (DHEA), DHEA-sulphate, and testosterone. We analysed data from the Childhood to Adolescence Transition Study (CATS), a longitudinal study of 1239 participants, recruited at 8-9 years old and followed up annually. Saliva samples were assayed for adrenal hormones. Linear mixed-effect models with subject-specific random intercepts and slopes were used to model longitudinal hormone trajectories by sex and derive measures of adrenarcheal timing and tempo. The median values for all hormones were higher at each consecutive study wave for both sexes, and higher for females than males. For all hormones, between-individual variation in hormone levels at age 9 (timing) was moderately large and similar for females and males. Between-individual variation in hormone progression over time (tempo) was of moderate magnitude compared with the population average age-slope, which itself was small compared with overall hormone level at each age. This suggests that between-individual variation in tempo was less important for modelling hormone trajectories. Between-individual variation in timing was more important for determining relative adrenal hormonal level in childhood than tempo. This finding suggests that adrenal hormonal levels at age 8-9 years can be used to predict relative levels in early adolescence (up to 13 years).
Topics: Male; Female; Animals; Adrenarche; Dehydroepiandrosterone; Longitudinal Studies; Prospective Studies; Dehydroepiandrosterone Sulfate
PubMed: 36520840
DOI: 10.1371/journal.pone.0278948