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1.
Sci Total Environ ; 918: 170621, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38316302

RESUMEN

PURPOSE: The aim of this study was to investigate the effect of solid fuel use on serum sex hormone levels. Furthermore, the effects of improved kitchen ventilation and duration of cooking time on the relationship between solid fuel use and serum sex hormone levels will be further explored. METHODS: In this cross-sectional study, 5386 individuals were recruited. Gender and menopausal status modified associations between solid fuel type and serum sex hormone levels was investigated through generalized linear models and further analyzed by improving kitchen ventilation and length of cooking time on the relationship between solid fuel use and serum sex hormone levels. To identify the causal association, mendelian randomization of two-sample was performed. RESULTS: In observational analyses, for ln-17-hydroxyprogesterone, ln-testosterone, and ln-androstenedione among premenopausal women, the estimated ß and 95 % CI of sex hormone levels for the effect of solid fuel users was -0.337 (-0.657, -0.017), -0.233 (-0.47, 0.005), and - 0.240 (-0.452, -0.028) respectively, and - 0.150 (-0.296, -0.004) in ln-progesterone among postmenopausal women. It was found that combining solid fuels with long cooking periods or no ventilation more effectively reduced testosterone and androstenedione in premenopausal women. We further found the adverse effects of using solid fuel on progesterone, testosterone, and androstenedione levels were enhanced with the increases of PM1, PM2.5, PM10, and NO2. Corresponding genetic, the causal risk effect of solid fuel were - 0.056 (-0.513, 0.4) and 0.026 (-3.495, 3.547) for testosterone levels and sex hormone binding globulin, respectively. CONCLUSION: Using gas or solid fuel was negatively related to sex hormone levels. A combination of using solid fuels, cooking for a long time, or cooking without ventilation had a stronger effect on sex hormone levels. However, genetic evidence did not support causality for the associations. WHAT IS ALREADY KNOWN ON THIS TOPIC?: The mechanisms underlying these associations household air pollution (HAP) from incomplete combustion of such fuels and occurrence of chronic diseases remained obscure. Recent years, extensive evidences from animal as well as human researches have suggested that progestogen and androgen hormones are involved in the development of diabetes, hypertension, and cardiovascular disease, which indicated that changes in serum progestogen and androgen hormones levels might play a role in these pathological mechanisms. However, limited evidence exists examining the effect of HAP from solid fuel use on serum sex hormone levels.


Asunto(s)
Contaminación del Aire Interior , Humanos , Femenino , Contaminación del Aire Interior/análisis , Estudios Transversales , Progesterona/análisis , Progestinas/análisis , Andrógenos/análisis , Androstenodiona/análisis , Análisis de la Aleatorización Mendeliana , Culinaria , Testosterona , China
2.
Clin Chem Lab Med ; 62(6): 1080-1091, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38205643

RESUMEN

OBJECTIVES: Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS). We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification. METHODS: Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by in-house and external calibration. Intra- and inter-laboratory performances were valued. RESULTS: Intra-laboratory CVs ranged between 4.2-13.2 % for androstenedione, 1.6-10.8 % for DHEAS, and 4.3-8.7 % and 2.6-7.1 % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 %. Median inter-laboratory CV with in-house vs. external calibration were 12.0 vs. 9.6 % for androstenedione (p<0.001), 7.2 vs. 4.9 % for DHEAS (p<0.001), 6.4 vs. 7.6 % for female testosterone (p<0.001) and 6.8 and 7.4 % for male testosterone (p=0.111). Median bias vs. all laboratory median with in-house and external calibration were -13.3 to 20.5 % and -4.9 to 18.7 % for androstenedione, -10.9 to 4.8 % and -3.4 to 3.5 % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 % for testosterone in females, and -7.0 to 8.5 % and -7.5 to 11.8 % for testosterone in males, respectively. CONCLUSIONS: Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.


Asunto(s)
Androstenodiona , Sulfato de Deshidroepiandrosterona , Espectrometría de Masas en Tándem , Testosterona , Androstenodiona/sangre , Androstenodiona/análisis , Testosterona/sangre , Testosterona/análisis , Testosterona/normas , Humanos , Espectrometría de Masas en Tándem/normas , Espectrometría de Masas en Tándem/métodos , Calibración , Masculino , Femenino , Cromatografía Liquida/normas , Cromatografía Liquida/métodos , Sulfato de Deshidroepiandrosterona/sangre , Sulfato de Deshidroepiandrosterona/análisis , Sulfato de Deshidroepiandrosterona/normas , Persona de Mediana Edad , Cromatografía Líquida con Espectrometría de Masas
3.
Environ Toxicol Chem ; 43(4): 915-925, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38085110

RESUMEN

Steroid hormones (SHs) have received widespread attention in recent years. However, current studies of SHs have primarily focused on estrogenic substances, with androgen-related studies being quite limited. We optimized the solid-phase extraction (SPE) pretreatment method, as well as the enzymolysis conditions of five androgens (androstenedione, boldenone, methandienone, nandrolone, and testosterone), to simultaneously determine their concentrations in the effluent from wastewater treatment plants and surface water samples. Then we evaluated the ecological risks of the five androgens in the effluent and Pearl River basin of Guangzhou (PR China) using the risk quotient method. The recovery rates of the targets were 90% to 99% in water samples when digested with ß-glucosidase for 90 min before solid-phase extraction, extracted with a Poly-Sery HLB column, and washed with 15% methanol aqueous solution and 2% ammonia. The established instrument's limit of detection was between 0.02 and 0.39 µg/L, and the limit of quantification was between 0.05 and 1.29 µg/L. Androstenedione, boldenone, methandienone, nandrolone, and testosterone were detected in all samples from the 2018 and 2022 wastewater influent and the 2018 surface water, with concentrations of 3.06 × 101 ng/L to 1.33 × 103 ng/L, 1.03-8.15 × 102 ng/L, and 0.93 × 101 ng/L to 5.50 × 102 ng/L, respectively. The ecological risks of androgens in wastewater influent and surface water were medium to high and low to medium, respectively. Moreover, the biotoxicity of androgens was predicted by the Ecological Structure Activity Relationships model, with methandienone and androstenedione having the highest and lowest acute and chronic toxicities, respectively. These results suggest that the risk of environmental androgens should not be ignored and that further research should be carried out. Environ Toxicol Chem 2024;43:915-925. © 2023 SETAC.


Asunto(s)
Metandrostenolona , Nandrolona , Contaminantes Químicos del Agua , Andrógenos , Aguas Residuales , Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas en Tándem/métodos , Androstenodiona/análisis , Metandrostenolona/análisis , Esteroides , Testosterona , Agua/química , Nandrolona/análisis , Extracción en Fase Sólida , Medición de Riesgo , Cromatografía Líquida de Alta Presión/métodos , Contaminantes Químicos del Agua/análisis
4.
Chemosphere ; 333: 138682, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37201600

RESUMEN

Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize wastewater-derived viral loads in local populations. Chemical tracers, both exogenous and endogenous compounds, have proven to be more stable and reliable for normalization than biological indicators. However, differing instrumentation and extraction methods can make it difficult to compare results. This review examines current extraction and quantification methods for ten common population indicators: creatinine, coprostanol, nicotine, cotinine, sucralose, acesulfame, androstenedione 5-hydroindoleacetic acid (5-HIAA), caffeine, and 1,7-dimethyluric acid. Some wastewater parameters such as ammonia, total nitrogen, total phosphorus, and daily flowrate were also evaluated. The analytical methods included direct injection, dilute and shoot, liquid/liquid, and solid phase extraction (SPE). Creatine, acesulfame, nicotine, 5-HIAA and androstenedione have been analysed by direct injection into LC-MS; however, most authors prefer to include SPE steps to avoid matrix effects. Both LC-MS and GC-MS have been successfully used to quantify coprostanol in wastewater, and the other selected indicators have been quantified successfully with LC-MS. Acidification to stabilize the sample before freezing to maintain the integrity of samples has been reported to be beneficial. However, there are arguments both for and against working at acidic pHs. Wastewater parameters mentioned earlier are quick and easy to quantify, but the data does not always represent the human population effectively. A preference for population indicators originating solely from humans is apparent. This review summarises methods employed for chemical indicators in wastewater, provides a basis for choosing an appropriate extraction and analysis method, and highlights the utility of accurate chemical tracer data for wastewater-based epidemiology.


Asunto(s)
COVID-19 , Contaminantes Químicos del Agua , Humanos , Aguas Residuales , Nicotina/análisis , ARN Viral , SARS-CoV-2 , Ácido Hidroxiindolacético/análisis , Androstenodiona/análisis , Colestanol/análisis , Pandemias , Contaminantes Químicos del Agua/análisis , COVID-19/epidemiología , Extracción en Fase Sólida/métodos , Indicadores y Reactivos
5.
J Endocrinol ; 258(2)2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37161994

RESUMEN

In birds, exposure to maternal (yolk) testosterone affects a diversity of offspring post-hatching traits, which eventually affect offspring competitiveness. However, maternal testosterone is heavily metabolized at very early embryonic developmental stages to hydrophilic metabolites that are often assumed to be much less biologically potent. Either the rapid metabolism could either keep the maternal testosterone from reaching the embryos, opening the possibility for a mother-offspring conflict or the metabolites may facilitate the uptake of the lipophilic testosterone from the yolk into the embryonic circulation after which they are either converted back to the testosterone or functioning directly as metabolites. To test these possibilities, we injected isotope-labeled testosterone (T-[D5]) into the yolk of freshly laid Rock pigeon (Columba livia) eggs and determined the concentration and distribution of T-[D5] and its labeled metabolites within different egg fractions by liquid chromatography combined with tandem mass spectrometry at day 2, 5 and 10 of incubation. Although under a supraphysiological dosage injection, yolk testosterone decreased within 2 days and was metabolized into androstenedione, conjugated testosterone, etiocholanolone and other components that were unidentifiable due to methodological limitation. We show for the first time that testosterone, androstenedione and conjugated testosterone, but not etiocholanolone, reached the embryo including its brain. Their high concentrations in the yolk and extraembryonic membranes suggest that conversion takes place here. We also found no sex-specific metabolism, explaining why maternal testosterone does not affect sexual differentiation. Our findings showed that maternal testosterone is quickly converted by the embryo, with several but not all metabolites reaching the embryo providing evidence for both hypotheses.


Asunto(s)
Andrógenos , Androstenodiona , Animales , Andrógenos/metabolismo , Androstenodiona/análisis , Androstenodiona/metabolismo , Columbidae/metabolismo , Herencia Materna , Testosterona/metabolismo , Yema de Huevo/química , Yema de Huevo/metabolismo
6.
Int J Mol Sci ; 23(23)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36499192

RESUMEN

The marked sexual dimorphism prevalent in inflammatory/autoimmune diseases is mostly due to sex hormone actions. One common eye disease that disproportionately affects women is dry eye. Thus, our aim was to optimise our highly sensitive liquid chromatography-tandem mass spectrometry method for steroid hormone quantification in tear fluid (TF). We used tears and matched serum samples from 10 heathy individuals. Estrone, estradiol testosterone, progesterone, androstenedione, and dehydroepiandrosterone, were quantified with an HPLC coupled with a Triple Quad 5500 MS. Estrone was measured in 80% of female and 20% of male TF samples (mean ± SD, 68.9 ± 62.2 pmol/L), whereas estradiol was undetectable in tears. Progesterone was identified in half of the female tear samples (2.91 ± 3.47 nmol/L) but in none of the male samples, whereas testosterone was quantifiable only in male tears (0.24 ± 0.1 nmol/L). TF hormone levels were, on average, from 1.4% to 55% of systemic values. Estrone, progesterone, and testosterone levels in tears correlated with the matching serum samples (r = 0.82, 0.79, and 0.85, respectively), but androstenedione and dehydroepiandrosterone showed no correlations. Our LC-MS/MS method could detect five out of the six steroid hormones studied in individual human TF samples and could therefore be used to analyse the role of sex steroids in eye diseases.


Asunto(s)
Estrona , Progesterona , Humanos , Femenino , Masculino , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Hormonas Esteroides Gonadales , Androstenodiona/análisis , Testosterona , Estradiol
7.
J Pharm Biomed Anal ; 215: 114768, 2022 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-35472830

RESUMEN

Hair steroid analysis offers the possibility to evaluate long-term steroid metabolism. It is especially beneficial when studying the steroid milieu in newborns and children, for example it can provide new insights into steroid metabolism over months and is unaffected by diurnal fluctuations in steroid concentrations. This study describes a quantitative and highly selective high-resolution mass spectrometry method for the simultaneous analysis of multiple steroids from human scalp hair. The developed method utilizes parallel reaction monitoring in the analysis of hydroxylamine derivatized steroids from hair samples first washed with isopropanol, extracted with methanol, and further purified with solid-phase extraction and liquid-liquid extraction. The method was proven suitable for the quantitative analysis of endogenous glucocorticoids (cortisol [1.5-364 pg/mg]; cortisone [3.6-355 pg/mg]; corticosterone [0.7-347 pg/mg]; 11-deoxycortisol [0.1-343 pg/mg]), androgens (testosterone [0.1-288 pg/mg]; dehydroepiandrosterone [0.3-288 pg/mg]; androstenedione [0.1-285 pg/mg]; 11ß-hydroxyandrostenedione [0.3-304 pg/mg]), progestogens (pregnenolone [0.1-313 pg/mg]; progesterone [0.1-313 pg/mg]; 17α-hydroxypregnenolone [0.3-315 pg/mg]; 17α-hydroxyprogesterone [0.7-330 pg/mg]; 21-hydroxyprogesterone [0.6-320 pg/mg]), and estrogens (estrone [0.1-267 pg/mg]; estradiol [0.5-274 pg/mg]). In addition, 11-ketoandrostenedione [0.6-60 pg/mg]; dihydrotestosterone [0.3-290 pg/mg]; 11-ketotestosterone [0.1-12 pg/mg]; and 5α-androstanedione [0.6-281 pg/mg] could be analyzed semi-quantitatively. Aldosterone [3.5-346 pg/mg]; 11ß-hydroxytestosterone [0.3-300 pg/mg]; and 11-ketodihydrotestosterone [0.3-300 pg/mg] were also included in the method, but their concentrations were below the lower limit of quantification in all tested hair samples. The method was applied for the analysis of authentic hair samples from different age groups ranging from newborns to adults, including mothers within 48 h after delivery. The newborn hair samples displayed the widest variety and had also the highest amounts of steroids in comparison to the samples of the other groups.


Asunto(s)
Cuero Cabelludo , Espectrometría de Masas en Tándem , Adulto , Andrógenos , Androstenodiona/análisis , Niño , Cromatografía Liquida/métodos , Cabello/química , Humanos , Recién Nacido , Cuero Cabelludo/química , Cuero Cabelludo/metabolismo , Esteroides/química , Espectrometría de Masas en Tándem/métodos
8.
Domest Anim Endocrinol ; 80: 106712, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35276581

RESUMEN

The various fibroblast growth factors (FGF) regulate their function via binding to 4 main FGF receptor (FGFR) subtypes and their splice variants, FGFR1b, FGF1c, FGFR2b, FGFR2c and FGFR3c and FGFR4, but which of these FGFR are expressed in the granulosa (GC) and theca cells (TC), the 2 main cell layers of ovarian follicles, or change during follicular development is unknown. We hypothesized that FGFR1c, FGFR2c and FGFR3c (but not FGFR4) gene expression in GC (but not TC) would change with follicular development. Hence, the objective of this study was to determine if abundance of FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in Holstein cattle exhibiting regular estrous cycles. Estrous cycles of non-lactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n = 8) or d 5 to 6 (n = 8) post-ovulation for GC and TC RNA extraction from small (1-5 mm), medium (5.1 to 8 mm) or large (8.1-18 mm) follicles for real-time PCR analysis. In GC, FGFR1c and FGFR2c mRNA relative abundance was greater in estrogen (E2)-inactive (ie, concentrations of E2 < progesterone, P4) follicles of all sizes than in GC from large E2-active follicles (ie, E2 > P4), whereas FGFR3c and FGFR4 mRNA abundance did not significantly differ among follicle types or days post-estrus. In TC, medium E2-inactive follicles had greater FGFR1c and FGFR4 mRNA abundance than large E2-active and E2-inactive follicles on d 5 to 6 post-ovulation whereas FGFR2c and FGFR3c mRNA abundance did not significantly differ among follicle types or day post-estrus. In vitro experiments revealed that androstenedione increased abundance of FGFR1c, FGFR2c and FGFR4 mRNA in GC whereas estradiol decreased FGFR2c mRNA abundance. Neither androstenedione nor estradiol affected abundance of the various FGFR mRNAs in cultured TC. Taken together, the findings that FGFR1c and FGFR2c mRNA abundance was less in GC of E2-active follicles and FGFR1c and FGFR4 mRNA was greater in TC of medium inactive follicles at late than at early growing phase of the first dominant follicle support an anti-differentiation role for FGF and their FGFR as well as support the idea that steroid-induced changes in FGF and their receptors may regulate selection of dominant follicles in cattle.


Asunto(s)
Androstenodiona , Células Tecales , Androstenodiona/análisis , Androstenodiona/metabolismo , Animales , Bovinos , Estradiol/metabolismo , Femenino , Células de la Granulosa/metabolismo , Ovario/metabolismo , ARN Mensajero/análisis , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Células Tecales/metabolismo
9.
Endocrinology ; 163(3)2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34999782

RESUMEN

A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.


Asunto(s)
Hormonas Esteroides Gonadales/análisis , Tejido Adiposo Blanco/química , Androstenodiona/análisis , Animales , Dihidrotestosterona/análisis , Estradiol/análisis , Estrona/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Hormonas Esteroides Gonadales/sangre , Hormonas Esteroides Gonadales/farmacocinética , Masculino , Ratones , Ratones Endogámicos C57BL , Orquiectomía , Progesterona/análisis , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/métodos , Testosterona/análisis , Distribución Tisular
10.
Biol Reprod ; 106(1): 118-131, 2022 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-34726240

RESUMEN

A population of cows with excess androstenedione (A4; High A4) in follicular fluid, with follicular arrest, granulosa cell dysfunction, and a 17% reduction in calving rate was previously identified. We hypothesized that excess A4 in the ovarian microenvironment caused the follicular arrest in High A4 cows and that vascular endothelial growth factor A would rescue the High A4 phenotype. In trial 1, prior to culture, High A4 ovarian cortex (n = 9) had greater numbers of early stage follicles (primordial) and fewer later-stage follicles compared to controls (n = 11). Culture for 7 days did not relieve this follicular arrest; instead, High A4 ovarian cortex had increased indicators of inflammation, anti-Mullerian hormone, and A4 secretion compared to controls. In trial 2, we tested if vascular endothelial growth factor A isoforms could rescue the High A4 phenotype. High A4 (n = 5) and control (n = 5) ovarian cortex was cultured with (1) PBS, (2) VEGFA165 (50 ng/mL), (3) VEGFA165B (50 ng/mL), or (4) VEGFA165 + VEGFA165B (50 ng/mL each) for 7 days. Follicular progression increased with VEGFA165 in High A4 cows with greater early primary, primary, and secondary follicles than controls. Similar to trial 1, High A4 ovarian cortex secreted greater concentrations of A4 and other steroids and had greater indicators of inflammation compared to controls. However, VEGFA165 rescued steroidogenesis, oxidative stress, and fibrosis. The VEGFA165 and VEGFA165b both reduced IL-13, INFα, and INFß secretion in High A4 cows to control levels. Thus, VEGFA165 may be a potential therapeutic to restore the ovarian steroidogenic microenvironment and may promote folliculogenesis.


Asunto(s)
Androstenodiona/análisis , Anovulación/veterinaria , Enfermedades de los Bovinos/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Folículo Ovárico/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Androstenodiona/metabolismo , Animales , Anovulación/tratamiento farmacológico , Anovulación/fisiopatología , Hormona Antimülleriana/metabolismo , Bovinos , Citocinas/metabolismo , Femenino , Fibrosis , Líquido Folicular/química , Folículo Ovárico/fisiopatología , Ovario/metabolismo , Ovario/patología , Estrés Oxidativo/efectos de los fármacos , Isoformas de Proteínas/administración & dosificación , Técnicas de Cultivo de Tejidos/veterinaria
11.
J Clin Endocrinol Metab ; 106(11): e4509-e4519, 2021 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-34165575

RESUMEN

CONTEXT: Several studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD). OBJECTIVE: To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional single-center study including 59 patients with classic 21OHD (men = 30; women = 29) and 49 body mass index- and age-matched controls (men = 19; women = 30). OUTCOME MEASURES: Salivary concentrations of the following steroids were analyzed by liquid chromatography-tandem mass spectrometry: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11ß-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). RESULTS: Similar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: mean reduction of hormone concentrations between timepoint 1 and 5 (Δ mean) in male patients = 66%; male controls Δ mean = 83%; female patients Δ mean = 47%; female controls Δ mean = 86%; 11KT: male patients Δ mean = 57%; male controls Δ mean = 63%; female patients Δ mean = 50%; female controls Δ mean = 76%). Significant correlations between the area under the curve for 17OHP and 11KT (rpmale = 0.773<0.0001; rpfemale = 0.737<0.0001), and 11OHA4 (rpmale = 0.6330.0002; rpfemale = 0.5640.0014) were observed in patients but not present or reduced in controls. CONCLUSIONS: Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.


Asunto(s)
Hiperplasia Suprarrenal Congénita/metabolismo , Andrógenos/análisis , Ritmo Circadiano/fisiología , Saliva/química , 17-alfa-Hidroxiprogesterona/análisis , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Adulto , Andrógenos/metabolismo , Androstenodiona/análogos & derivados , Androstenodiona/análisis , Biomarcadores/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Testosterona/análogos & derivados , Testosterona/análisis
12.
Int J Mol Sci ; 22(2)2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33418978

RESUMEN

The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate cancer (CRPC). De novo steroidogenesis has been identified as a key mechanism that develops during CRPC. Currently, there is very limited information available on human prostate tissue steroidogenesis. The purpose of the present study was to investigate steroid metabolism in human prostate cancer tissues with comparison between PZ and TZ. Human prostate cancer tumors were procured from the patients who underwent radical prostatectomy without any neoadjuvant therapy. Human prostate homogenates were used to quantify steroid levels intrinsically present in the tissues as well as formed after incubation with 2 µg/mL of 17-hydroxypregnenolone (17-OH-pregnenolone) or progesterone. A Waters Acquity ultraperformance liquid chromatography coupled to a Quattro Premier XE tandem quadrupole mass spectrometer using a C18 column was used to measure thirteen steroids from the classical and backdoor steroidogenesis pathways. The intrinsic prostate tissue steroid levels were similar between PZ and TZ with dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), pregnenolone and 17-OH-pregnenolone levels higher than the other steroids measured. Interestingly, 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one, and 5-pregnan-17-ol-3,20-dione formation was significantly higher in both the zones of prostate tissues, whereas, androstenedione, testosterone, DHT, and progesterone levels were significantly lower after 60 min incubation compared to the 0 min control incubations. The incubations with progesterone had a similar outcome with 5-pregnan-3,20-dione and 5-pregnan-3-ol-20-one levels were elevated and the levels of DHT were lower in both PZ and TZ tissues. The net changes in steroid formation after the incubation were more observable with 17-OH-pregnenolone than with progesterone. In our knowledge, this is the first report of comprehensive analyses of intrinsic prostate tissue steroids and precursor-driven steroid metabolism using a sensitive liquid chromatography-mass spectrometry assay. In summary, the PZ and TZ of human prostate exhibited similar steroidogenic ability with distinction in the manner each zone utilizes the steroid precursors to divert the activity towards backdoor pathway through a complex matrix of steroidogenic mechanisms.


Asunto(s)
Neoplasias de la Próstata/patología , Esteroides/metabolismo , Androstenodiona/análisis , Androsterona/análisis , Cromatografía Líquida de Alta Presión , Humanos , Masculino , Espectrometría de Masas , Progesterona/análogos & derivados , Progesterona/análisis , Progesterona/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata/metabolismo , Esteroides/análisis , Esteroides/química , Testosterona/análisis
13.
Rapid Commun Mass Spectrom ; 34(24): e8937, 2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-32876355

RESUMEN

RATIONALE: The aromatase inhibitor formestane (4-hydroxyandrost-4-ene-3,17-dione) is included in the World Anti-Doping Agency's List of Prohibited Substances in Sport. However, it also occurs endogenously as do its 2-, 6- and 11-hydroxy isomers. The aim of this study is to distinguish the different isomers using gas chromatography/electron ionization mass spectrometry (GC/EI-MS) for enhanced confidence in detection and selectivity for determination. METHODS: Established derivatization protocols to introduce [2 H9 ]TMS were followed to generate perdeuterotrimethylsilylated and mixed deuterated derivatives for nine different hydroxy steroids, all with 3-keto-4-ene structure. Formestane was additionally labelled with H2 18 O to obtain derivatives doubly labelled with [2 H9 ]TMS and 18 O. GC/EI-MS spectra of labelled and unlabelled TMS derivatives were compared. Proposals for the generation of fragment ions were substantiated by high-resolution MS (GC/QTOFMS) and tandem mass spectrometry (MS/MS) experiments. RESULTS: Subclass-specific fragment ions include m/z 319 for the 6-hydroxy and m/z 219 for the 11-hydroxy compounds. Ions at m/z 415, 356, 341, 313, 269 and 267 were indicative for the 2- and 4-hydroxy compounds. For their discrimination the transition m/z 503 → 269 was selective for formestane. In 2-, 4- and 6-hydroxy steroids loss of a TMSO radical takes place as cleavage of a TMS-derived methyl radical and a neutral loss of (CH3 )2 SiO. Further common fragments were also elucidated. CONCLUSIONS: With the help of stable isotope labelling, the structures of postulated diagnostic fragment ions for the different steroidal subclasses were elucidated. 18 O-labelling of the other compounds will be addressed in future studies to substantiate the obtained findings. To increase method sensitivity MS3 may be suitable in future bioanalytical applications requiring discrimination of the 2- and 4-hydroxy compounds.


Asunto(s)
Androstenodiona/análogos & derivados , Cromatografía de Gases y Espectrometría de Masas/métodos , Esteroides/análisis , Espectrometría de Masas en Tándem/métodos , Androstenodiona/análisis , Androstenodiona/química , Doping en los Deportes , Esteroides/química
14.
Sci Rep ; 10(1): 2954, 2020 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-32075989

RESUMEN

The blubber steroid hormone profiles of 52 female humpback whales migrating along the east coast of Australia were investigated for seasonal endocrine changes associated with reproduction. Individuals were randomly sampled during two stages of the annual migration: before reaching the breeding grounds (northward migration; June/July), and after departing from the breeding grounds (southward migration; September/October). Assignment of reproductive status of the sampled individuals was based on season, single-hormone ranks and multi-variate analysis of the hormonal profiles. High concentrations of progesterone (>19 ng/g, wet weight), recognised as an indicator of pregnancy in this species, were only detected in one sample. However, the androgens, testosterone and androstenedione were measured in unusually high concentrations (1.6-12 and 7.8-40 ng/g wet weight, respectively) in 36% of the females approaching the breeding grounds. The absence of a strong accompanying progesterone signal in these animals raises the possibility of progesterone withdrawal prior to parturition. As seen with other cetacean species, testosterone and androstenedione could be markers of near-term pregnancy in humpback whales. Confirmation of these androgens as alternate biomarkers of near-term pregnancy would carry implications for improved monitoring of the annual fecundity of humpback whales via non-lethal and minimally invasive methods.


Asunto(s)
Androstenodiona/análisis , Yubarta/fisiología , Pruebas de Embarazo/métodos , Grasa Subcutánea/química , Testosterona/análisis , Animales , Biomarcadores/análisis , Femenino , Embarazo , Progesterona/análisis , Estaciones del Año
15.
Sci Total Environ ; 671: 248-253, 2019 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-30928753

RESUMEN

Endogenous chemicals specific to human metabolism have been suggested to be good candidates for markers of population size in wastewater-based epidemiology (WBE). So far, creatinine is the only endogenous chemical to be assessed against the criteria of in-sewer stability. This study thus aimed to evaluate the fate of three other endogenous compounds, 5-hydroxy indole acetic acid (5-HIAA), cortisol and androstenedione, under different sewer conditions using laboratory-scale sewer reactors. The results showed that while all compounds were stable in wastewater only (i.e. without biofilm), cortisol and androstenedione degraded quickly in sewers with the presence of sewer biofilms. The degradation followed first-order kinetics similar to that of creatinine. In contrast, 5-HIAA was relatively stable in sewer reactors. This study also recognised the impact of wastewater pH on the detectability of 5-HIAA using a LC-MS/MS direct injection method. In samples acidified to pH 2, the method did not allow routine detection/quantification of 5-HIAA whereas in non-acidified samples the method was sufficiently sensitive for routine quantification of 5-HIAA. The stability of 5-HIAA in sewers and the possibility to measure it using a simple and rapid analytical method corroborate that 5-HIAA may be a suitable biomarker for estimation of population size in WBE.


Asunto(s)
Androstenodiona/análisis , Monitoreo del Ambiente/métodos , Hidrocortisona/análisis , Ácido Hidroxiindolacético/análisis , Aguas Residuales/análisis , Contaminantes Químicos del Agua/análisis , Biomarcadores/análisis
16.
J Pediatr Endocrinol Metab ; 32(3): 287-294, 2019 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-30811345

RESUMEN

Background During pubertal development in healthy boys, increased levels of different sex steroids occur which are responsible for sexual maturation and physical changes. However, relationships between various sex hormones and pubertal development stages have not been sufficiently studied. Methods The investigation included 165 normal boys (mean age 12.7±2.8 years, mean body mass index [BMI] 19.6±4.2 kg/m2). Pubic hair (PH) stages were stratified by Tanner and testicular volume (TV) by means of the Prader orchidometer and assigned to the prepubertal, pubertal and postpubertal development phase. Four different sex steroids (testosterone [TE], dehydroepiandrosterone [DHEA]/dehydroepiandrosterone-sulfate [DHEAS], androstenedione (AE), 17-hydroxyprogesterone [17-OHP]) were measured in saliva by enzyme-linked immunosorbent assay (ELISA) and as serum total steroids by different assays (radioimmunoassay [RIA], chemiluminescence immunoassay [CLIA], electrochemiluminescence immunoassay [ECLIA]). Validation of saliva-based ELISA tests included data related to inter- and intra-assay coefficients of variation (CVs), recovery and linearity. Results Using Spearman rank correlation, salivary steroids significantly correlated (p<0.001) with pubertal development: TE (TV r=0.74 and PH stages r=0.72), DHEA (r=0.58 and 0.62), AE (r=0.38 and 0.45) and 17-OHP (r=0.42 and 0.43). Correlations between salivary and serum concentrations of steroids were also statistically significant (p<0.001). Binomial logistic regression analysis revealed significant correlations between salivary TE and pubertal maturation during the development phases of prepuberty-puberty and puberty-postpuberty. Inclusion of further salivary steroids did not improve analysis results. Conclusions Salivary TE permits a good non-invasive characterization of pubertal maturation stages. The consideration of further salivary sex steroids did not improve diagnostic accuracy.


Asunto(s)
17-alfa-Hidroxiprogesterona/análisis , Androstenodiona/análisis , Sulfato de Deshidroepiandrosterona/análisis , Deshidroepiandrosterona/análisis , Pubertad/metabolismo , Saliva/química , Testosterona/análisis , Adolescente , Niño , Humanos , Masculino
17.
Reprod Biomed Online ; 38(1): 30-37, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30527851

RESUMEN

RESEARCH QUESTION: Can IVF outcomes be predicted from the steroid profile generated by liquid chromatography-mass spectrometry (LC-MS/MS) from follicular fluid collected from a single dominant follicle and serum after ovarian stimulation. DESIGN: Prospective observational cohort study in which serum and follicular fluid were collected from women and used to generate steroid profiles by LC-MS/MS. A total of 93 consecutive women enrolled for IVF treatment were recruited at the Fertility Unit, Royal Prince Alfred Women and Babies Hospital, Sydney between September 2014 and July 2015. Baseline and serum levels at oocyte retrieval, as well as follicular fluid samples from the largest single antral follicle, were collected. All samples underwent steroid analysis within a single batch to measure progesterone (P4), oestradiol (E2), oestrone (E1), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), dihydrotestosterone (DHT), and 3 α, 5α androstanediol (3α-diol) and 3ß, 5α androstanediol (3ß-diol). RESULTS: P4, E2, E1, A4, T, DHEA and A4 were detectable in all baseline serum levels, at oocyte retrieval and in follicular fluid samples, whereas DHT, 3α-diol and 3ß-diol were only detectable in a minority of samples. The most consistent predictor of pre-transfer (number of follicles >14mm in diameter, oocytes retrieved or fertilized, day-5 blastocysts) outcomes was baseline serum anti-Müllerian hormone. In follicular fluid, E2 was a negative predictor of the number of oocytes retrieved and the number of day-5 blastocysts but no follicular fluid steroids predicted pregnancy outcome. CONCLUSIONS: None of the nine steroids measured in follicular fluid predicted pregnancy outcome in women undergoing IVF.


Asunto(s)
Andrógenos/análisis , Estrógenos/análisis , Líquido Folicular/química , Progesterona/análisis , Progestinas/análisis , Adulto , Andrógenos/sangre , Androstenodiona/análisis , Androstenodiona/sangre , Cromatografía Liquida , Deshidroepiandrosterona/análisis , Deshidroepiandrosterona/sangre , Dihidrotestosterona/análisis , Dihidrotestosterona/sangre , Estradiol/análisis , Estradiol/sangre , Estrógenos/sangre , Estrona/análisis , Estrona/sangre , Femenino , Fertilización In Vitro , Humanos , Espectrometría de Masas , Progesterona/sangre , Progestinas/sangre , Testosterona/análisis , Testosterona/sangre
18.
Rev. chil. endocrinol. diabetes ; 12(1): 11-15, 2019. tab, ilus
Artículo en Español | LILACS | ID: biblio-982011

RESUMEN

Clinical case: a girl of 7 ½ years who consulted for early pubarche without thelark, with a percentile size of 75 for a genetic target size in the 10th percentile, overweight with a 90th percentile BMI, and normal blood pressure. The biochemical study showed high levels of androgens: testosterone: 7.2 ng/dL, androstenedione of 5.1 ng / ml, 17OHP: 15 ng / dL with low normal DHEAS (0.26 ug/ml), Plasma Renin Activity normal low: 0.22 ng/mL/h. Initial imaging study showed a bone age of 10 years 6 months and normal abdominal and pelvic ultrasound. Molecular study showed no pathogenic variants in the CYP21A2 gene (21 Hydroxylase). With a probable diagnosis of non-classical congenital adrenal hyperplasia (HSRNC) and no known mutation, he started treatment with hydrocortisone (12 mg/m2). At 8.7 years, pubertal development begins and braking begins with LHRH analogues, which are administered for 18 months. Despite the treatment, signs of virilization and elevation of androgens (testosterone up to 130 ng/ml) are progressively accentuated, which do not diminish when trying different corticosteroid schemes. MRI of the abdomen and pelvis shows the normal adrenal glands and a solid nodular image of 2.1 x 1.6 cm in the right ovary (Figure 2), later demonstrated with pelvic ultrasound (Figure 2). Right laparoscopic oophorectomy was performed, whose biopsy demonstrated a Leydig cell tumor. One month after surgery, all androgenic levels were normalized, so the gradual suspension of corticosteroids began. Conclusion: Although HSRNC is the most frequent pathological cause of early pubarche, when it is associated with progressive clinical and biochemical hyperandrogenism despite adequate treatment and without pathogenic variants in the CYP21A2 gene, even with high levels of 17OHP, other causes should be considered, specifically, androgen producing tumors.


Caso clínico: niña de 7½ años que consulta por pubarquia precoz sin telarquia, con talla en percentil 75 para una talla objetivo genético en percentil 10, sobrepeso con IMC percentil 90 y presión arterial normal. El estudio bioquímico mostró niveles elevados de andrógenos: testosterona: 7,2 ng/dL, androstenediona de 5,1 ng/ml, 17OHP: 15 ng/dL con DHEAS normal baja (0,26 ug/ml), Actividad de Renina Plasmática normal baja: 0.22 ng/ mL/h. Estudio de imágenes inicial mostró una edad ósea de 10 años 6 meses y ecografía abdominal y pelviana normales. Estudio molecular no mostró variantes patogénicas en el gen CYP21A2 (21 Hidroxilasa). Con diagnosticó probable de hiperplasia suprarrenal congénita no clásica (HSRNC) y sin mutación conocida,inició el tratamiento con hidrocortisona (12 mg/m2). A los 8.7 años comienza desarrollo puberal y se inicia frenación con análogos de LHRH, los cuales se administran por 18 meses. A pesar del tratamiento se acentúan progresivamente los signos de virilización y hayelevación de los andrógenos (testosterona hasta 130 ng/ml), que no disminuyen intentando diferentes esquemas de corticoides. Se realiza RM de abdomen y pelvis que muestra las glándulas suprarrenales normales y una imagen nodular sólida de 2.1 x 1.6 cm en el ovario derecho (Figura 2), demostrada posteriormente con Ecografía pelviana (Figura 2). Se realiza ooforectomía derecha por vía laparoscópica, cuya biopsia demostró un tumor de células de Leydig. Un mes después de la cirugía, se normalizan todos los niveles androgénicos por lo que se inició la suspensión gradual de los corticoides. Conclusión: Aunque la HSRNC es la causa patológica más frecuente de la pubarquia precoz, cuando se asocia con un hiperandrogenismo clínico y bioquímico progresivo a pesar de un tratamiento adecuado y sin variantes patógenicas en el gen CYP21A2, incluso con niveles elevados de 17OHP, otras causas deben ser consideradas, específicamente tumores productores de andrógenos.


Asunto(s)
Humanos , Femenino , Niño , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico , Pubertad Precoz/etiología , Tumor de Células de Leydig/complicaciones , Tumor de Células de Leydig/diagnóstico , Testosterona/análisis , Hiperandrogenismo/etiología , Hiperplasia Suprarrenal Congénita/diagnóstico , 17-alfa-Hidroxiprogesterona/análisis , Hirsutismo/etiología , Andrógenos/análisis , Androstenodiona/análisis
19.
J Chromatogr A ; 1566: 51-63, 2018 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-29958683

RESUMEN

Anabolic and androgenic steroids (AAS) are banned substances in both human and equine sports. They are often administered intramuscularly to horses in esterified forms for the purpose of extending their time of action. The authors' laboratory has previously reported an UHPLC/HRMS method using quadrupole-Orbitrap mass spectrometer in full scan and parallel reaction monitoring (PRM) mode for the detection of 48 AAS and/or their esters in horse hair. However, two injections were required due to the long duty cycle time. In this paper, an UHPLC/HRMS method using multiplexed targeted MS2 mode was developed and validated to improve the coverage to 65 AAS and/or their esters in a single injection. In addition, a GC/MS/MS method in selected reaction monitoring (SRM) mode was developed to screen for another seven AAS and/or their esters not adequately covered by the UHPLC/HRMS method using the same sample extract after derivatisation with pentafluoropropionic anhydride. The UHPLC/HRMS and GC/MS/MS methods in combination allowed the detection of 72 AAS and/or their esters with estimated limits of detection down to sub to low ppb levels with good interday precision. Method applicability was demonstrated by the detection of boldione and 4-androstenedione in two out-of-competition hair samples and testosterone propionate in a referee hair sample.


Asunto(s)
Cromatografía Líquida de Alta Presión , Ésteres/análisis , Cromatografía de Gases y Espectrometría de Masas , Cabello/química , Esteroides/análisis , Espectrometría de Masas en Tándem , Androstenodiona/análisis , Animales , Doping en los Deportes , Ésteres/química , Caballos , Esteroides/química , Propionato de Testosterona/análisis
20.
Steroids ; 138: 26-34, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29864449

RESUMEN

BACKGROUND: Recently, measurements of steroids like testosterone, androstenedione, cortisol and cortisone in saliva are more and more applied in diagnostics and scientific studies. This is mainly due to the simple and non-invasive collection of saliva. We aimed to evaluate the optimal way to collect saliva for steroid hormone measurement. METHODS: We investigated in twenty volunteers whether there is a difference between steroid hormone concentrations in unstimulated and stimulated saliva collected while chewing, using cotton and synthetic Salivettes®, citric acid or chewing gum. Furthermore, total unstimulated saliva was compared to parotid gland saliva. Testosterone, androstenedione, cortisol and cortisone were measured using Liquid-Chromatography Tandem Mass Spectrometry (LC-MS/MS). RESULTS: Salivary testosterone, androstenedione and cortisol concentrations were unaffected by stimulation upon mouth and tongue movements, cortisone levels were on average 16% lower. Concentrations of all hormones were lower in parotid gland saliva compared to total unstimulated saliva (on average 51%, 26%, 66% and 49% lower, for testosterone, androstenedione, cortisol and cortisone, respectively). Concentrations of testosterone as well as androstenedione were lower when using synthetic Salivettes® (58% and 41%, respectively) and were higher when using cotton Salivettes® (217% and 46%, respectively). Cortisol levels in saliva were unaffected by using Salivettes®. However, cortisol and testosterone levels were higher in with chewing gum stimulated saliva (16% and 55%, respectively). Cortisone concentrations were lower in all types of stimulations (on average 25%-35%). CONCLUSION: The way saliva is collected should be considered when analysing and interpreting salivary hormone concentrations. We advocate unstimulated saliva collection in simple polypropylene tubes for all steroid measurements.


Asunto(s)
Androstenodiona/análisis , Cortisona/análisis , Hidrocortisona/análisis , Saliva/química , Esteroides/análisis , Testosterona/análisis , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
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