Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.
A development of robust and rapid method with simple sample preparation for the analysis of steroids of C18-, C19-, C21- families is of interest of many research groups. Here we present a novel LC-MS/MS method for the simultaneous quantification of 32 steroid hormones in human plasma. Twenty-two of them were analyzed directly without the need for derivatization, while ten were derivatized with 2-fluoro-1-methylpyridinium p-toluenesulfonate. The steroids were separated on a C18 column with a gradient elution consisting of methanol and water with the addition of 0.1% formic acid. The mass spectrometer was operated in positive ESI mode. Validation demonstrated that the method was applicable for the quantitative analysis of two C18- steroids (estrone, estradiol), nineteen C19- steroids (testosterone, epitestosterone, dihydrotestosterone, 11-ketodihydrotestosterone, 11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketotestosterone, dehydroepiandrosterone, 7α-hydroxydehydroepiandrosterone, 7β-hydroxydehydroepiandrosterone, 7-ketodehydroepiandrosterone, androsterone, epiandrosterone, androstenedione, androstenediol, 5α-androstane-3α,17β-diol, 5α-androstane-3β,17β-diol, 5β-androstane-3α,17β-diol, 5β-androstane-3β,17β-diol), and eleven C21- steroids (cortisol, 21-deoxycortisol, 11-deoxycortisol, cortisone, corticosterone, 11-deoxycorticosterone, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 5α-dihydroprogesterone). The lower limits of quantification are appropriate for analyses in both physiological and various pathophysiological conditions. The accuracy, intra- and inter-day precision values as well as stability tests were in accordance with FDA Guidelines. The method will be a useful tool in investigating the mechanisms of steroid-related diseases and will serve as a steppingstone for the development of other methods for steroid analyses in various biological matrices such as prostate tissue, cerebrospinal fluid, urine, seminal fluid, and saliva.
- MeSH
- androgeny MeSH
- androstendion * MeSH
- chromatografie kapalinová metody MeSH
- estron MeSH
- lidé MeSH
- tandemová hmotnostní spektrometrie * metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: There is strong epidemiologic evidence indicating that estrogens may not be the sole steroid drivers of breast cancer. We hypothesize that abundant adrenal androgenic steroid precursors, acting via the androgen receptor (AR), promote an endocrine-resistant breast cancer phenotype. EXPERIMENTAL DESIGN: AR was evaluated in a primary breast cancer tissue microarray (n = 844). Androstenedione (4AD) levels were evaluated in serum samples (n = 42) from hormone receptor-positive, postmenopausal breast cancer. Levels of androgens, progesterone, and estradiol were quantified using LC/MS-MS in serum from age- and grade-matched recurrent and nonrecurrent patients (n = 6) before and after aromatase inhibitor (AI) therapy (>12 months). AR and estrogen receptor (ER) signaling pathway activities were analyzed in two independent AI-treated cohorts. RESULTS: AR protein expression was associated with favorable progression-free survival in the total population (Wilcoxon, P < 0.001). Pretherapy serum samples from breast cancer patients showed decreasing levels of 4AD with age only in the nonrecurrent group (P < 0.05). LC/MS-MS analysis of an AI-sensitive and AI-resistant cohort demonstrated the ability to detect altered levels of steroids in serum of patients before and after AI therapy. Transcriptional analysis showed an increased ratio of AR:ER signaling pathway activities in patients failing AI therapy (t test P < 0.05); furthermore, 4AD mediated gene changes associated with acquired AI resistance. CONCLUSIONS: This study highlights the importance of examining the therapeutic consequences of the steroid microenvironment and demonstrable receptor activation using indicative gene expression signatures.
- MeSH
- androgenní receptory fyziologie MeSH
- androstendion krev fyziologie MeSH
- chemorezistence MeSH
- inhibitory aromatasy terapeutické užití MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buňky kultivované MeSH
- nádory prsu krev farmakoterapie etiologie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has become apparent that those compounds that naturally occur in animals can also be found as natural constituents of plants and vice versa, i.e., they have essentially the same fate in the majority of living organisms. This review summarizes the current state of knowledge on the occurrence of animal steroid hormones in the plant kingdom, particularly focusing on progesterone, testosterone, androstadienedione (boldione), androstenedione, and estrogens.
- MeSH
- androstadieny metabolismus MeSH
- androstendion biosyntéza MeSH
- biosyntetické dráhy MeSH
- estrogeny biosyntéza MeSH
- fytosteroly metabolismus MeSH
- progesteron biosyntéza MeSH
- rostliny metabolismus MeSH
- steroidy biosyntéza MeSH
- testosteron biosyntéza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The androgens dehydroepiandrosterone sulfate, dehydro-epiandrosterone, androstenedione and testosterone are routinely assessed in women, and circulating levels of these androgens reflect their production. These androgens are measured in most laboratories using various immuno-analytical methods. Recently, however, androgen assays have begun to be performed using gas or liquid chromatography combined with mass spectrometry. To better understand the difficulties and issues of androgen laboratory diagnostics, it is important to assess each of the methods used, how and why they were introduced into practice, and their advantages, limits, historic milestones and current status. It is also necessary to understand how reference ranges are determined and specifics arising from the physiology of individual androgens. Here we present a summary and discussion of these issues.
- MeSH
- androgeny krev MeSH
- androstendion krev MeSH
- biologické markery krev MeSH
- chromatografie kapalinová normy MeSH
- dehydroepiandrosteron krev MeSH
- hmotnostní spektrometrie normy MeSH
- lidé MeSH
- nemoci endokrinního systému krev diagnóza MeSH
- referenční hodnoty MeSH
- testosteron krev MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- přehledy MeSH
Smoking during pregnancy presents health risks for both the mother and her child. In this study we followed changes in the production of steroid hormones in pregnant smokers. We focused on changes in steroidogenesis in the blood of mothers in their 37(th) week of pregnancy and in mixed cord blood from their newborns. The study included 88 healthy women with physiological pregnancies (17 active smokers and 71 non-smokers). We separately analyzed hormonal changes associated with smoking according to the sex of newborns. In women with male fetuses, we found higher levels of serum cortisone, dehydroepiandrosterone (DHEA), 7alpha-OH-DHEA, 17-OH pregnenolone, testosterone, and androstenedione in smokers at the 37(th) week compared to non-smokers. In women with female fetuses, we found lower serum levels of 7beta-OH-DHEA and higher androstenedione in smokers at the 37(th) week. We found significantly higher levels of testosterone in newborn males of smokers and higher levels of 7alpha-OH-DHEA in female newborns of smokers. Smoking during pregnancy induces changes in the production of steroids in both the mother and her child. These changes are different for different fetal sexes, with more pronounced changes in mothers carrying male newborns as well as in the newborn males themselves.
- MeSH
- androstendion krev MeSH
- dehydroepiandrosteron analogy a deriváty krev MeSH
- dehydroepiandrosteronsulfát krev MeSH
- dospělí MeSH
- estradiol krev MeSH
- fetální krev metabolismus MeSH
- kouření škodlivé účinky metabolismus MeSH
- lidé MeSH
- novorozenec MeSH
- plod metabolismus MeSH
- průzkumy a dotazníky MeSH
- steroidy krev MeSH
- těhotenství MeSH
- testosteron krev MeSH
- zpožděný efekt prenatální expozice krev etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- algoritmy MeSH
- androstendion * krev MeSH
- dehydroepiandrosteronsulfát * krev MeSH
- dospělí MeSH
- estradiol * krev MeSH
- estron * krev MeSH
- F faktor MeSH
- globulin vázající pohlavní hormony * analýza MeSH
- kohortové studie MeSH
- lidé MeSH
- polysomnografie MeSH
- poruchy iniciace a udržování spánku epidemiologie krev patofyziologie MeSH
- poruchy spánku a bdění epidemiologie krev patofyziologie MeSH
- poruchy spánku z vnitřních příčin * epidemiologie krev patofyziologie MeSH
- prevalence MeSH
- průřezové studie MeSH
- stupeň závažnosti nemoci MeSH
- syndromy spánkové apnoe epidemiologie krev patofyziologie MeSH
- testosteron * MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
- souhrny MeSH
- Geografické názvy
- Německo MeSH
The metabolism of steroids and retinoids has been studied in detail for a long time, as these compounds are involved in a broad spectrum of physiological processes. Many enzymes participating in the conversion of such compounds are members of the short-chain dehydrogenase/reductase (SDR) superfamily. Despite great effort, there still remain a number of poorly characterized SDR proteins. According to various bioinformatics predictions, many of these proteins may play a role in the metabolism of steroids and retinoids. Dehydrogenase/reductase (SDR family) member 7 (DHRS7) is one such protein. In a previous study, we determined DHRS7 to be an integral membrane protein of the endoplasmic reticulum facing the lumen which has shown at least in vitro NADPH-dependent reducing activity toward several eobiotics and xenobiotics bearing a carbonyl moiety. In the present paper pure DHRS7 was used for a more detailed study of both substrate screening and an analysis of kinetics parameters of the physiologically important substrates androstene-3,17-dione, cortisone and all-trans-retinal. Expression patterns of DHRS7 at the mRNA as well as protein level were determined in a panel of various human tissue samples, a procedure that has enabled the first estimation of the possible biological function of this enzyme. DHRS7 is expressed in tissues such as prostate, adrenal glands, liver or intestine, where its activity could be well exploited. Preliminary indications show that DHRS7 exhibits dual substrate specificity recognizing not only steroids but also retinoids as potential substrates and could be important in the metabolism of these signalling molecules.
- MeSH
- androstendion metabolismus MeSH
- cirkulární dichroismus MeSH
- fylogeneze MeSH
- kinetika MeSH
- kortison metabolismus MeSH
- lidé MeSH
- oxidoreduktasy chemie genetika metabolismus MeSH
- regulace genové exprese enzymů MeSH
- retinaldehyd metabolismus MeSH
- steroidy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Exogenous substances altering the function of the endocrine system and exhibiting adverse health effects on the organism are defined as endocrine disruptors. Nonylphenol is one of the most abundant alkylphenol ethoxylate derivatives, being detected in food products. Diverse studies have classified nonylphenol as hazardous to the health, especially to male reproduction. This in vitro study aimed to examine the effects of 4-nonylphenol on androstenedione and testosterone production as well as on the viability of Leydig cells of NMRI mice. The cells were cultured for 44 h with addition of 0.04; 0.2; 1.0; 2.5 and 5.0 μg/ml of 4-nonylphenol and compared to the control. Quantification of testosterone and androstenedione directly from aliquots of the medium was performed by enzyme-linked immunosorbent assay. Cell viability was measured by the metabolic activity assay for mitochondrial functional activity. Androstenedione production significantly (P < 0.001) increased with 1.0; 2.5 and 5.0 μg/ml 4-nonylphenol. Although cAMP-stimulated testosterone production was not significantly affected by 4-nonylphenol, a tendency to attenuate the level of testosterone in the Leydig cells treated with 2.5 and 5.0 μg/ml 4-nonylphenol was observed. The viability of mouse Leydig cells was slightly increased at the lowest doses of 4-nonylphenol (0.04 and 0.2 μg/ml). We also observed an increase at higher concentrations of the substance (1.0; 2.5 and 5.0 μg/ml), but this increase was not significant. Further investigations are required to establish the biological significance and possible reproductive implications.
- MeSH
- AMP cyklický metabolismus MeSH
- androstendion biosyntéza MeSH
- fenoly farmakologie MeSH
- hormony biosyntéza MeSH
- kultivované buňky MeSH
- Leydigovy buňky cytologie účinky léků MeSH
- myši MeSH
- testosteron biosyntéza MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Syndróm polycystických ovárií (PCOS) je najčastejšou endokrinopatiou u žien fertilného veku a najčastejšou príčinou porúch menštruačného cyklu. Je charakterizovaný hyperandrogénnym stavom (klinickým alebo biochemickým) a ovariálnou dysfunkciou (anovuláciou alebo ultrasonografickým nálezom polycystických ovárií), čo sú zároveň kritériá pre jeho diagnózu podľa Androgen Excess and PCOS Society. Syndróm má mnohopočetné fenotypové prejavy, medzi ktoré patrí okrem uvedených charakteristík aj metabolický syndróm, predovšetkým obezita a inzulínová rezistencia. Diagnóza PCOS je v klinickej praxi pomerne náročná a stále platí, že je diagnózou per exclusionem, po vylúčení iných príčin hyperandrogénneho stavu a chronickej oligo-anovulácie. Vyžaduje si úzku spoluprácu gynekológa, endokrinológa a z hľadiska častých metabolických komplikácií aj internistu, diabetológa a prípadne aj kardiológa. Kľúčové slová: AES kritériá – diagnóza – diferenciálna diagnóza – syndróm polycystických ovárií
Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist. Key words: AES criteria – diagnosis – differential diagnosis – polycystic ovary syndrome
- MeSH
- alopecie etiologie MeSH
- androstendion analýza MeSH
- anovulace etiologie MeSH
- antimülleriánský hormon analýza MeSH
- diferenciální diagnóza MeSH
- hirzutismus etiologie MeSH
- hyperandrogenismus diagnóza MeSH
- lidé MeSH
- menstruační poruchy etiologie MeSH
- syndrom polycystických ovarií * diagnóza patofyziologie ultrasonografie MeSH
- testosteron analýza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
