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Nutrients Dec 2021Red meat (RM) consumption is correlated with multiple health outcomes. This study aims to identify potential biomarkers of RM consumption in the Chinese population and...
Red meat (RM) consumption is correlated with multiple health outcomes. This study aims to identify potential biomarkers of RM consumption in the Chinese population and evaluate their predictive ability. We selected 500 adults who participated in the 2015 China Health and Nutrition Survey and examined their overall metabolome differences by RM consumption by using elastic-net regression, then evaluate the predictivity of a combination of filtered metabolites; 1108 metabolites were detected. In the long-term RM consumption analysis 12,13-DiHOME, androstenediol (3α, 17α) monosulfate 2, and gamma-Glutamyl-2-aminobutyrate were positively associated, 2-naphthol sulfate and S-methylcysteine were negatively associated with long-term high RM consumption, the combination of metabolites prediction model evaluated by area under the receiver operating characteristic curve (AUC) was 70.4% (95% CI: 59.9-80.9%). In the short-term RM consumption analysis, asparagine, 4-hydroxyproline, and 3-hydroxyisobutyrate were positively associated, behenoyl sphingomyelin (d18:1/22:0) was negatively associated with short-term high RM consumption. Combination prediction model AUC was 75.6% (95% CI: 65.5-85.6%). We identified 10 and 11 serum metabolites that differed according to LT and ST RM consumption which mainly involved branch-chained amino acids, arginine and proline, urea cycle and polyunsaturated fatty acid metabolism. These metabolites may become a mediator of some chronic diseases among high RM consumers and provide new evidence for RM biomarkers.
Topics: Adult; Amino Acids; Aminobutyrates; Androstenediols; Asian People; Biomarkers; China; Cysteine; Diet; Fatty Acids, Unsaturated; Female; Humans; Lipids; Male; Metabolomics; Middle Aged; ROC Curve; Red Meat; Sulfuric Acid Esters; Surveys and Questionnaires
PubMed: 34960119
DOI: 10.3390/nu13124567 -
Genes & Development Dec 2023Reductions in brain kynurenic acid levels, a neuroinhibitory metabolite, improve cognitive function in diverse organisms. Thus, modulation of kynurenic acid levels is...
Reductions in brain kynurenic acid levels, a neuroinhibitory metabolite, improve cognitive function in diverse organisms. Thus, modulation of kynurenic acid levels is thought to have therapeutic potential in a range of brain disorders. Here we report that the steroid 5-androstene 3β, 17β-diol (ADIOL) reduces kynurenic acid levels and promotes associative learning in We identify the molecular mechanisms through which ADIOL links peripheral metabolic pathways to neural mechanisms of learning capacity. Moreover, we show that in aged animals, which normally experience rapid cognitive decline, ADIOL improves learning capacity. The molecular mechanisms that underlie the biosynthesis of ADIOL as well as those through which it promotes kynurenic acid reduction are conserved in mammals. Thus, rather than a minor intermediate in the production of sex steroids, ADIOL is an endogenous hormone that potently regulates learning capacity by causing reductions in neural kynurenic acid levels.
Topics: Animals; Kynurenic Acid; Steroids; Hormones; Mammals
PubMed: 38092521
DOI: 10.1101/gad.350745.123 -
Cell May 2011Microglia and astrocytes play essential roles in the maintenance of homeostasis within the central nervous system, but mechanisms that control the magnitude and duration...
Microglia and astrocytes play essential roles in the maintenance of homeostasis within the central nervous system, but mechanisms that control the magnitude and duration of responses to infection and injury remain poorly understood. Here, we provide evidence that 5-androsten-3β,17β-diol (ADIOL) functions as a selective modulator of estrogen receptor (ER)β to suppress inflammatory responses of microglia and astrocytes. ADIOL and a subset of synthetic ERβ-specific ligands, but not 17β-estradiol, mediate recruitment of CtBP corepressor complexes to AP-1-dependent promoters, thereby repressing genes that amplify inflammatory responses and activate Th17 T cells. Reduction of ADIOL or ERβ expression results in exaggerated inflammatory responses to TLR4 agonists. Conversely, the administration of ADIOL or synthetic ERβ-specific ligands that promote CtBP recruitment prevents experimental autoimmune encephalomyelitis in an ERβ-dependent manner. These findings provide evidence for an ADIOL/ERβ/CtBP-transrepression pathway that regulates inflammatory responses in microglia and can be targeted by selective ERβ modulators.
Topics: 17-Hydroxysteroid Dehydrogenases; Alcohol Oxidoreductases; Androstenediol; Animals; Astrocytes; Cells, Cultured; DNA-Binding Proteins; Encephalomyelitis, Autoimmune, Experimental; Estrogen Receptor beta; Humans; Inflammation; Mice; Mice, Inbred C57BL; Microglia; Neurodegenerative Diseases; Proto-Oncogene Proteins c-fos; Signal Transduction
PubMed: 21565615
DOI: 10.1016/j.cell.2011.03.050 -
Menopause (New York, N.Y.) Jun 2012The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids...
OBJECTIVE
The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids that have the potential to alter estrogen/androgen balance and explain the wide interwoman range of estrogen-related symptoms experienced during the MT.
METHODS
Annual serum samples from the Study of Women's Health Across the Nation, which had previously been analyzed for immunoreactive estradiol (E2), testosterone, DHEAS, and sex hormone-binding globulin, were selected based on DHEAS concentration and analyzed for immunoreactive and bioactive estrogens and androgens, including immunoreactive androstenedione, dehydroepiandrosterone, and 5-androstene-3β,17β-diol (androstenediol [Adiol]).
RESULTS
A two-fold increase in circulating androstenedione and testosterone was found to rise in parallel with the rise in circulating DHEAS, whereas dehydroepiandrosterone and Adiol concentrations rose seven- to eight-fold. Circulating Adiol, which has both androgenic and estrogenic biological activity, was significantly associated (P < 0.02) with circulating estrogen bioactivity only when E2 concentrations were low and Adiol levels were high.
CONCLUSIONS
The wide range of circulating levels of Adiol and its contribution to total circulating estrogenicity during the MT is consistent with the observed interwoman difference in symptoms at this time. Therefore, we conclude that Adiol contributes to circulating estrogenicity when E2 production falls at menopause and may contribute significantly to the endocrine changes experienced by midlife women.
Topics: Adult; Androstenediol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Humans; Middle Aged; Perimenopause; Testosterone
PubMed: 22415563
DOI: 10.1097/gme.0b013e31823df577 -
The Journal of Biological Chemistry Apr 1975Cellular protein binding of a number of androstene and androstane derivatives that promote the growth of the vagina in rats has been studied. It was found that cell...
Cellular protein binding of a number of androstene and androstane derivatives that promote the growth of the vagina in rats has been studied. It was found that cell nuclei of the rat vagina contain a tissue-specific protein that binds 3beta,17beta-dihydroxy-androst-5-ene (delta5-androstenediol), a unique steroid causing growth and keratinization of the vaginal epithelium. The formation of the steroid-protein complex can be demonstrated by the administration of delta5-[3H]androstenediol to ovariectomized rats or by the incubation of minced vagina with the radioactive steroid. The steroid can interact with purified vaginal cell nuclei even in the absence of a cytosol preparation, forming the same steroid-protein complex. The formation of the complex is temperature-dependent; it occurs much more readily at 37 degrees than at 0 degrees. The delta5-[3H]androstenediol-protein complex migrated as about 4 S in a sucrose gradient medium containing 0.4 M KCl. A similar complex can be detected when nuclei of vaginal cells are incubated with 3alpha,17beta-dihydroxy-5alpha-androstane, 3beta,17beta-dihydroxy-5alpha-androstane, and 3beta-hydroxy-androst-5-en-17-one which also have the capability of stimulating vaginal epithelium, although in somewhat different ways. These steroids may bind to different groups of chromatin-bound receptor proteins in various layers of vaginal epithelium. The delta5-androstenediol binding protein is not found in the vaginal cytosol fraction that contains receptor proteins for estrogens and progestins, nor in the cytosol or nuclei of rat uterus cells, but not in muscle, brain, kidney, or liver. Testosterone and 5alpha-dihydrostestosterone bind weakly to the protein, whereas cortisol, androstenedione, 17beta-estradiol, and progesterone do not bind to the same protein by any significant extent.
Topics: Androstenediols; Animals; Binding Sites; Castration; Cell Nucleus; Centrifugation, Density Gradient; Cytosol; Female; Kidney; Kinetics; Liver; Macromolecular Substances; Organ Specificity; Ovary; Protein Binding; Proteins; Rats; Receptors, Cell Surface; Temperature; Uterus; Vagina
PubMed: 164458
DOI: No ID Found -
Menopause (New York, N.Y.) Jun 2012It is now recognized that mean circulating dehydroepiandrosterone sulfate (DHEAS) concentrations in most midlife women exhibit a positive inflection starting in early...
OBJECTIVE
It is now recognized that mean circulating dehydroepiandrosterone sulfate (DHEAS) concentrations in most midlife women exhibit a positive inflection starting in early perimenopause, continuing through early postmenopause and returning to early perimenopausal levels by late postmenopause. This rise in mean DHEAS is accompanied by concomitant rises in testosterone (T), dehydroepiandrosteone (DHEA), and androstenedione (Adione) and an equal rise in androstenediol (Adiol). These observations suggest that there is a specific relationship between the circulating levels of steroids emanating from the adrenal glands, declining ovarian function, and the stages of the menopausal transition. This study was designed to test the hypothesis that the menopausal stage-specific change in circulating DHEAS is associated with concomitant changes in the circulating pattern of adrenal steroids and that some of these adrenal androgens could influence the circulating estrogen/androgen balance.
METHODS
Stored annual serum samples (N = 120) were first selected to represent four longitudinal DHEAS profiles of individual women to assess and compare changes in the adrenal contribution to circulating steroids.
RESULTS
Changes in mean circulating DHEAS levels in midlife women during the menopausal transition is associated with changes in mean circulating T, Adione, and Adiol. Mean Adione and T concentrations changed the least, whereas mean DHEAS and Adiol changed the most.
CONCLUSIONS
Changes in circulating steroid hormone emanating from the adrenal during the menopausal transition may be more important than the decline in ovarian function in terms of altering the estrogen/androgen balance.
Topics: Adrenal Glands; Adult; Androgens; Androstenediol; Androstenedione; Cohort Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Humans; Hydrocortisone; Longitudinal Studies; Middle Aged; Perimenopause; Testosterone
PubMed: 22415570
DOI: 10.1097/gme.0b013e31823fe274 -
Toxicology and Applied Pharmacology May 2024Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line...
BACKGROUND
Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line pharmacological treatments include acetazolamide and topiramate and given the nature of IIH patients and the dosing regimen of these drugs, their effect on the endocrine system is important to evaluate. We aimed to assess the effects of acetazolamide and topiramate on steroid profiles in relevant endocrine tissues.
METHODS
Female Sprague Dawley rats received chronic clinically equivalent doses of acetazolamide or topiramate by oral gavage and were sacrificed in estrus. Tissue specific steroid profiles of lateral ventricle CP, 4th ventricle CP, CSF, serum, uterine horn and fundus, ovaries, adrenal glands and pituitary glands were assessed by quantitative targeted LC-MS/MS. We determined luteinizing hormone (LH) and follicle stimulating hormones (FSH) levels in paired serum by ELISA.
RESULTS
Topiramate increased the concentration of estradiol and decreased the concentration of DHEA in lateral choroid plexus. Moreover, it decreased the concentration of androstenediol in the pituitary gland. Topiramate increased serum LH. Acetazolamide decreased progesterone levels in serum and uterine fundus and increased corticosteroid levels in the adrenal glands.
CONCLUSION
These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.
Topics: Animals; Female; Topiramate; Rats, Sprague-Dawley; Acetazolamide; Endocrine Disruptors; Rats; Estrus; Luteinizing Hormone; Fructose; Pituitary Gland; Progesterone; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Estradiol; Ovary
PubMed: 38580201
DOI: 10.1016/j.taap.2024.116919 -
Frontiers in Chemistry 2022Accurate investigation of adrenal hormone levels plays a vital role in pediatric endocrinology for the detection of steroid-related disorders. This study aims to develop...
Simultaneous quantitation of 17 endogenous adrenal corticosteroid hormones in human plasma by UHPLC-MS/MS and their application in congenital adrenal hyperplasia screening.
Accurate investigation of adrenal hormone levels plays a vital role in pediatric endocrinology for the detection of steroid-related disorders. This study aims to develop a straightforward, sensitive UHPLC-MS/MS method to quantify 17 endogenous adrenal corticosteroid hormones in human plasma. These hormones are the main ingredients in the synthetic and metabolic pathways of adrenal corticosteroid hormones. Chromatographic separation was achieved on a C18 column before electrospray ionization triple-quadrupole mass spectrometry in multiple reaction monitoring mode with a run time of 7 min. The samples were extracted by liquid-liquid extraction and required no derivatization. Analytical performance was evaluated, including linearity, analytical sensitivity, accuracy, precision, and specificity. Plasma specimens from 32 congenital adrenal hyperplasia (CAH) patients and 30 healthy volunteers were analyzed to further reveal the diagnostic value of multiple steroid hormones in the synthetic and metabolic pathways of adrenal corticosteroid in CAH diagnosis. All hormones were effectively extracted and separated using our method. The method was essentially free from potential interference of isomers or structural analogues. The imprecisions were <10%. The lower limits of quantification varied from 0.05 to 15.0 ng/ml. Good linearity coefficients ( > 0.998) were also obtained for most hormones in the required concentration range, except for 21-deoxycortisol ( = 0.9967) and androstenediol ( = 0.9952). The recoveries for the steroid hormones ranged from 91.7 to 109.8%. We developed the UHPLC-MS/MS method for the simultaneous measurement of steroid hormones. The results showed that measurement of steroid hormones simultaneously could improve the diagnostic efficiency of CAH.
PubMed: 36034654
DOI: 10.3389/fchem.2022.961660 -
Endocrinology Apr 2008Stimulation of prostate growth is a major concern with testosterone therapy in older hypogonadal men. As a result, nonsteroidal selective androgen receptor modulators...
Tissue selectivity of the anabolic steroid, 19-nor-4-androstenediol-3beta,17beta-diol in male Sprague Dawley rats: selective stimulation of muscle mass and bone mineral density relative to prostate mass.
Stimulation of prostate growth is a major concern with testosterone therapy in older hypogonadal men. As a result, nonsteroidal selective androgen receptor modulators with anabolic activity but less prostate stimulation are being developed. Anabolic steroids might exhibit similar tissue selectivity. We hypothesized the anabolic steroid 19-nor-4-androstenediol-3beta,17beta-diol (3beta,19-NA) would increase muscle, lean body mass (LBM), and bone mineral density (BMD) with little stimulation of prostate growth. Male Sprague Dawley rats were implanted with SILASTIC brand (Dow Corning, Midland, MI) capsules containing 3beta,19-NA (4, 8, or 16 cm), dihydrotestosterone (DHT) (8 cm), 19-nortestosterone (16 cm), or four empty capsules after undergoing either a sham operation (intact) or orchidectomy (ORX). Serum gonadotropins, measured after 4, 8, or 24 wk of treatment, were significantly lower in 3beta,19-NA-treated vs. untreated, intact, and ORX rats (P < 0.05), and testosterone was lowered by 3beta,19-NA-treatment of intact animals. LBM and BMD were assessed after 20 wk, and 4 wk later, rats were killed for levator ani muscle and prostate weights. Compared with ORX rats, 3beta,19-NA-treated rats had dose-dependent higher levator ani muscle weights, LBM, and BMD, which were similar to intact and DHT-treated rats at the highest 3beta,19-NA dose. In contrast, prostate weights in all 3beta,19-NA-treated groups were similar to ORX rats and lower than intact and DHT- and 19-nortestosterone-treated rats even at the highest 3beta,19-NA dose. In summary, 3beta,19-NA increases muscle and bone mass without significant stimulation of prostate growth, suggesting it may have some properties of a steroidal selective androgen receptor modulator. Anabolic steroids such as 3beta,19-NA should be studied further to determine their mechanisms of tissue selectivity and effects in men.
Topics: Androstenediols; Animals; Body Composition; Bone Density; Hypothalamo-Hypophyseal System; Male; Muscle, Skeletal; Organ Specificity; Prostate; Rats; Rats, Sprague-Dawley
PubMed: 18096666
DOI: 10.1210/en.2007-0956 -
Fertility and Sterility Sep 1981
Review
Topics: Adrenal Gland Diseases; Androgens; Androstenediol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Female; Hirsutism; Humans; Infertility; Male; Menstruation Disturbances; Ovarian Diseases; Testosterone
PubMed: 6456938
DOI: 10.1016/s0015-0282(16)45728-6