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Pharmacology & Therapeutics Oct 2007Neurosteroids are a relatively new class of neuroactive compounds brought to prominence in the past 2 decades. Despite knowing of their presence in the nervous system of... (Review)
Review
Neurosteroids are a relatively new class of neuroactive compounds brought to prominence in the past 2 decades. Despite knowing of their presence in the nervous system of various species for over 20 years and knowing of their functions as GABA(A) and N-methyl-d-aspartate (NMDA) ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of 4 distinct neurosteroids: pregnenolone, progesterone, allopregnanolone, and dehydroepiandrosterone (DHEA).
Topics: Animals; Central Nervous System; Dehydroepiandrosterone; Humans; Pregnanolone; Pregnenolone; Progesterone; Steroids; Synaptic Transmission
PubMed: 17651807
DOI: 10.1016/j.pharmthera.2007.04.011 -
Proceedings of the National Academy of... Apr 1998
Review
Topics: Animals; Brain; Cholesterol Side-Chain Cleavage Enzyme; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Gene Expression Regulation, Developmental; Humans; Signal Transduction; Steroid 17-alpha-Hydroxylase
PubMed: 9539693
DOI: 10.1073/pnas.95.8.4089 -
Hormones (Athens, Greece) Mar 2023
Topics: Humans; Hydrocortisone; COVID-19; Dehydroepiandrosterone Sulfate; Dehydroepiandrosterone
PubMed: 36374475
DOI: 10.1007/s42000-022-00417-3 -
Archives of Disease in Childhood Aug 1982
Topics: Age Factors; Breast; Child; Child, Preschool; Dehydroepiandrosterone; Female; Humans; Infant; Puberty, Precocious
PubMed: 6214219
DOI: 10.1136/adc.57.8.642 -
Hormones and Behavior Jul 2015Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may have mood enhancement effects: higher DHEAS concentrations and DHEA/cortisol ratio have been... (Randomized Controlled Trial)
Randomized Controlled Trial
Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may have mood enhancement effects: higher DHEAS concentrations and DHEA/cortisol ratio have been related to lower depression scores and controlled trials of DHEA administration have reported significant antidepressant effects. The balance between DHEAS and DHEA has been suggested to influence brain functioning. We explored DHEAS, DHEA, cortisol, DHEA/cortisol and DHEAS/DHEA ratios relations to the processing of negative emotional stimuli at behavioral and brain levels by recording the electroencephalogram of 21 young women while performing a visual task with implicit neutral or negative emotional content in an audio-visual oddball paradigm. For each condition, salivary DHEA, DHEAS and cortisol were measured before performing the task and at 30 and 60min intervals. DHEA increased after task performance, independent of the implicit emotional content. With implicit negative emotion, higher DHEAS/DHEA and DHEA/cortisol ratios before task performance were related to shorter visual P300 latencies suggesting faster brain processing under a negative emotional context. In addition, higher DHEAS/DHEA ratios were related to reduced visual P300 amplitudes, indicating less processing of the negative emotional stimuli. With this study, we could show that at the electrophysiological level, higher DHEAS/DHEA and DHEA/cortisol ratios were related to shorter stimulus evaluation times suggesting less interference of the implicit negative content of the stimuli with the task. Furthermore, higher DHEAS/DHEA ratios were related to reduced processing of negative emotional stimuli which may eventually constitute a protective mechanism against negative information overload.
Topics: Adolescent; Adult; Behavior; Brain Waves; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Electrocardiography; Emotional Intelligence; Emotions; Female; Humans; Hydrocortisone; Reaction Time; Young Adult
PubMed: 26122298
DOI: 10.1016/j.yhbeh.2015.06.005 -
Environmental Research Dec 2022Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels.
OBJECTIVE
We conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women.
METHODS
We included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors.
RESULTS
In premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results.
CONCLUSION
Our findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.
Topics: Androgens; Androstenedione; Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Estrone; Female; Gonadal Steroid Hormones; Humans; Sex Hormone-Binding Globulin; Testosterone
PubMed: 36088991
DOI: 10.1016/j.envres.2022.114285 -
Hormones (Athens, Greece) Jun 2023Hyperandrogenism, one of the most frequent causes of anovulation in women, increases the risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS)....
PURPOSE
Hyperandrogenism, one of the most frequent causes of anovulation in women, increases the risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS). Ferroptosis, characterized by iron-dependent lipid peroxidation, has provided new insight into the progression of PCOS. 1,25-dihydroxyvitamin D3 (1,25D3) may play a role in reproduction because its receptor, VDR, which contributes to the inhibition of oxidative stress, is primarily located in the nuclei of granulosa cells. This study has therefore investigated whether 1,25D3 and hyperandrogenism affect granulosa-like tumor cells (KGN cells) through ferroptosis.
METHODS
KGN cells were treated with dehydroepiandrosterone (DHEA) or pretreated with 1,25D3. Cell viability was evaluated with the cell counting kit-8 (CCK-8) assay. The mRNA and protein expression levels of ferroptosis-related molecules, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member (SLC7A11), and long-chain acyl-CoA synthetase 4 (ACSL4), were assessed via qRT-PCR and western blot. The concentration of malondialdehyde (MDA) was measured by ELISA. The rates of reactive oxygen species (ROS) production and lipid peroxidation were assessed via photometric methods.
RESULTS
Decreased cell viability, suppression of GPX4 and SLC7A11 expression, increased expression of ACSL4, elevated levels of MDA, accumulation of ROS, and increased lipid peroxidation, which are changes representative of ferroptosis, were observed in KGN cells after treatment with DHEA. Pretreatment with 1,25D3 in KGN cells significantly prevented these changes.
CONCLUSIONS
Our findings demonstrate that 1,25D3 attenuates hyperandrogen-induced ferroptosis of KGN cells. This finding might lead to new insights into the pathophysiology and therapy of PCOS and provides new evidence for the treatment of PCOS with 1,25D3.
Topics: Humans; Female; Calcitriol; Ferroptosis; Reactive Oxygen Species; Hyperandrogenism; Polycystic Ovary Syndrome; Dehydroepiandrosterone
PubMed: 36884209
DOI: 10.1007/s42000-023-00439-5 -
Aging Cell Aug 2004Aging is associated with a decline in immunity described as immunosenescence. This is paralleled by a decline in the production of several hormones, as typically... (Review)
Review
Aging is associated with a decline in immunity described as immunosenescence. This is paralleled by a decline in the production of several hormones, as typically illustrated by the menopausal loss of ovarian oestrogen production. However, other hormonal changes that occur with aging and that potentially impact on immune function include the release of the pineal gland hormone melatonin and pituitary growth hormone, adrenal production of dehydroepiandrosterone and tissue-specific availability of active vitamin D. It remains to be established whether hormonal changes with aging actually contribute to immunosenescence and this area is at the interface of fact and fiction, clearly inviting systematic research efforts. As a step in this direction, the present review summarizes established facts on the physiology of secretion and function of hormones that, in most cases, decline with aging and that are likely to affect the immune system.
Topics: Aging; Calcitriol; Dehydroepiandrosterone; Hormones; Human Growth Hormone; Humans; Immunity; Melatonin; Models, Biological
PubMed: 15268754
DOI: 10.1111/j.1474-9728.2004.00109.x -
Fertility and Sterility Aug 2004Review of literature with regard to androgen replacement therapy in women. (Review)
Review
OBJECTIVE
Review of literature with regard to androgen replacement therapy in women.
DESIGN
Review of the MEDLINE database and references from articles.
CONCLUSIONS
Androgens affect sexual function, bone health, muscle mass, body composition, mood, energy, and the sense of well-being. Androgen insufficiency clearly has been demonstrated in patients with hypopituitarism, adrenalectomy, oophorectomy, and in some women placed on oral estrogen therapy which increases sex hormone-binding globulin (SHBG) levels and lowers the free and bioavailable forms of T. Symptoms of androgen insufficiency in women may include a diminished sense of well-being, low mood, fatigue, and hypoactive sexual desire disorder with decreased libido, or decreased sexual receptivity and pleasure that causes a great deal of personal distress. The preponderance of evidence from clinical trials supports the correlation of decreased endogenous androgen levels with these symptoms and alleviation of many of the symptoms with the administration of T or, in some cases, DHEA. There are no Food and Drug Administration-approved androgen preparations on the market for treating androgen insufficiency in women. The safety profile of androgens in doses used for the treatment of hypoactive sexual desire disorder has been excellent with only mild acne and hirsutism being noted in a minority of patients.
Topics: Androgens; Clinical Trials as Topic; Dehydroepiandrosterone; Female; Hormone Replacement Therapy; Humans; MEDLINE; Sexuality
PubMed: 15302268
DOI: 10.1016/j.fertnstert.2003.11.062 -
The Netherlands Journal of Medicine Sep 2005Dehydroepiandrosterone (DHEA) and its ester dehydroepiandrosterone sulphate (DHEAS) are produced by the adrenal glands. These hormones are inactive precursors that are... (Review)
Review
Dehydroepiandrosterone (DHEA) and its ester dehydroepiandrosterone sulphate (DHEAS) are produced by the adrenal glands. These hormones are inactive precursors that are transformed into active sex steroids in peripheral target tissues. After a peak in early adulthood, there is a marked decrease in plasma concentrations throughout adult life. These hormones are thought to affect mood and well-being, have neurosteroid effects and may influence the immune system. Animal experiments suggest that DHEA has many other effects, including anticancer, immune-enhancing, neurotropic and general antiageing effects, but information based on studies in humans is limited. In female patients with adrenal insufficiency, treatment with DHEA replacement doses of 20 to 50 mg results in improvements in mood, quality of life and libido. These studies usually lasted only a few months, so the effect of chronic DHEA treatment or its effectiveness in male patients is not known. Some studies suggest a favourable effect of pharmacological doses of DHEA in the treatment of depression. DHEA may have a very limited effect on cognitive function in elderly people, and some studies suggest a beneficial immunomodulatory effect of DHEA in patients with autoimmune diseases, but further studies are warranted before introducing DHEA for these indications in clinical practice.
Topics: Adrenal Insufficiency; Affect; Age Factors; Autoimmune Diseases; Cognition; Dehydroepiandrosterone; Evidence-Based Medicine; Female; Humans; Male; Postmenopause
PubMed: 16186639
DOI: No ID Found