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| 3. |
- Bergquist, Maria, et al.
(author)
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Altered adrenal and gonadal steroids biosynthesis in patients with burn injury
- 2016
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In: Clinical Mass Spectrometry. - : Elsevier BV. - 2213-8005 .- 2376-9998. ; 1, s. 19-26
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Journal article (peer-reviewed)abstract
- Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury.Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry.Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OH-pregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury.Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesis driven study.
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| 4. |
- Ericsson, Maria, et al.
(author)
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Domestication effects on behavioural and hormonal responses to acute stress in chickens
- 2014
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In: Physiology and Behavior. - : Elsevier BV. - 0031-9384 .- 1873-507X. ; 133, s. 161-169
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Journal article (peer-reviewed)abstract
- Comparative studies have shown that alterations in physiology, morphology and behaviour have arisen due to the domestication. A driving factor behind many of the changes could be a shift in stress responses, with modified endocrine and behavioural profiles. In the present study we compared two breeds of chicken (Gallus gallus), the domestic White Leghorn (WL) egg laying breed and its ancestor, the Red Junglefowl (RJF). Birds were exposed to an acute stress event, invoked by 3 or 10 min of physical restraint. They were then continuously monitored for the effects on a wide range of behaviours during a 60 min recovery phase. Blood samples were collected from the chicken at baseline, and after 10 and 60 min following a similar restraint stress, and the samples were analyzed for nine endogenous steroids of the HPA and HPG axes. Concentration of the steroids was determined using validated liquid chromatography tandem mass spectrometry methods. In RJF, an immediate behavioural response was observed after release from restraint in several behaviours, with a relatively fast return to baseline within 1 h. In WL, some behaviours were affected for a longer period of time, and others not at all. Concentrations of corticosterone increased more in RJF, but returned faster to baseline compared to WL. A range of baseline levels for HPG-related steroids differed between the breeds, and they were generally more affected by the stress in WL than in RJF. In conclusion, RJF reacted stronger both behaviourally and physiologically to the restraint stress, but also recovered faster. This would appear to be adaptive under natural conditions, whereas the stress recovery of domesticated birds has been altered by domestication and breeding for increased reproductive output.
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| 5. |
- Grönbladh, Alfhild, et al.
(author)
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The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats
- 2013
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In: Steroids. - : Elsevier. - 0039-128X .- 1878-5867. ; 78:12-13, s. 1192-1199
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Journal article (peer-reviewed)abstract
- Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC-MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17- hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. controls, AAS, rhGH and the combination of AAS and rhGH treatment.
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| 9. |
- Kushnir, Mark M., et al.
(author)
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Beta-methylamino-L-alanine analysis by liquid chromatography tandem mass spectrometry with iTRAQ as the derivative
- 2009
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In: European journal of mass spectrometry. - : SAGE Publications. - 1469-0667 .- 1751-6838. ; 15:3, s. 439-443
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Journal article (peer-reviewed)abstract
- Amino acid BMMA is produced by cyanobacteria and has been linked to the development of neurodegenerative diseases. We developed a method for quantitative analysis of BMAA in biological samples and plant extracts. The method is utilizing iTRAQ and LC-MS/MS detection using multiple reaction monitoring mode. The method uses 50 pL of sample and has a Limit of quantitation of 300 ng mL(-1), within-run run imprecision below 1%. Using this method we analyzed human serum samples, human cerebrospinal fluid samples and extract of the cycad seed. No BMAA could be detected in the human samples. Content of BMAA in the seed was 50 mg kg(-1).
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| 12. |
- Kushnir, Mark M., et al.
(author)
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Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment
- 2016
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In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 162, s. 126-133
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Research review (peer-reviewed)abstract
- Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF.
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| 13. |
- Kushnir, Mark M., et al.
(author)
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High-Sensitivity Tandem Mass Spectrometry Assay for Serum Estrone and Estradiol
- 2008
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In: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 129:4, s. 530-539
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Journal article (peer-reviewed)abstract
- High-sensitivity measurement of serum estrogens is important in adult and pediatric endocrinology and oncology. We developed a high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of estrone (E-1) and estradiol (E-2). Aliquots of 200 mu L of serum were spiked with internal standard, extracted, derivatized with dansyl chloride, and analyzed by LC-MS/MS using 2-dimensional chromatographic separation. Total imprecision for the method was less than 11%; the limit of quantitation was 1 pg/mL. Reference intervals were established with samples from more than 900 healthy postmenopausal women, men, girls, and boys. Concentrations of estrogens in children reached adult levels by Tanner stage 3. In men and postmenopausal women, the median concentrations of total estrogens (E-1 + E-2) were 39 and 22 pg/mL, and the median E-2/E-1 ratios were 0.98 and 0.55, respectively. The method requires a small sample volume and has adequate sensitivity and specificity for analyzing estrogens in samples from postmenopausal women, men, and children.
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| 14. |
- Kushnir, Mark M., et al.
(author)
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LC-MS/MS in clinical laboratories
- 2013
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In: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 5:1, s. 5-6
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Journal article (peer-reviewed)
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| 15. |
- Kushnir, Mark M., et al.
(author)
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Liquid chromatography-tandem mass spectrometry applications in endocrinology
- 2010
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In: Mass spectrometry reviews (Print). - : Wiley. - 0277-7037 .- 1098-2787. ; 29:3, s. 480-502
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Research review (peer-reviewed)abstract
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC-MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on-line and off-line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC-MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles.
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| 16. |
- Kushnir, Mark M., et al.
(author)
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Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories
- 2011
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 44:1, s. 77-88
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Research review (peer-reviewed)abstract
- Liquid chromatography tandem mass spectrometry is one of the most specific techniques available in clinical laboratories. In the past, immunoassays were the primary methodology for analysis of steroids in biological samples because they are rapid and easy to perform. However, these methods were shown to suffer from the lack of specificity for measuring many of the diagnostically important steroids. LC-MS/MS overcomes many of the limitations of immunoassays, enhances diagnostic utility of the testing, and expands diagnostic capabilities in endocrinology. In addition to the superior quality of the measurements, LC-MS/MS allows high throughput testing using small sample volume with minimal sample preparation, and frees the laboratory from dependence on suppliers of assay specific reagents. LC-MS/MS is being widely employed for routine measurement of steroids, and the methodology plays an important role in the standardization and harmonization of measurements among clinical laboratories.
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| 17. |
- Kushnir, Mark M., 1957-
(author)
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Mass Spectrometric Applications for Diagnosing Metabolic and Endocrine Diseases
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Disease-specific compounds (biomarkers) are analyzed in clinical laboratories to assist with diagnosing diseases. This thesis describes development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS) based tests for diagnosing a diverse group of endocrine and metabolic diseases. The analytical methods used on-line and off-line sample extraction and analytical derivatization as means of enhancing the analytical sensitivity, specificity and clinical utility. All developed methods were extensively validated and reference intervals for the biomarker concentrations were established in blood samples of healthy adults and children. Advantages of the LC-MS/MS as an analytical technique include possibility of simultaneous measurement of multiple analytes and ability of confirming their identity. In this thesis we proposed and evaluated approaches for the assessment of the specificity of analysis in the methods that use tandem mass spectrometry detection. To enhance throughput of the LC-MS/MS tests for the biomarkers that have endogenous or exogenous isomers an approach was developed for quantitation of isomers from unresolved chromatographic peaks. Using methods developed in this thesis we performed a study of the steroidogenesis in ovarian follicles of healthy women and women with polycystic ovary syndrome (PCOS). Obtained data on the steroid concentrations and associations between the steroid metabolites in the pathway would be helpful for better understanding of the ovarian pathophysiology. Potential biomarkers of PCOS were identified in the thesis; further studies will be necessary to confirm their clinical utility.
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| 18. |
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| 19. |
- Kushnir, Mark M., et al.
(author)
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Protein and Steroid Profiles in Follicular Fluid after Ovarian Hyperstimulation as Potential Biomarkers of IVF Outcome
- 2012
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:10, s. 5090-5100
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Journal article (peer-reviewed)abstract
- Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocy-te retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.
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| 20. |
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| 21. |
- Kushnir, Mark M, et al.
(author)
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Steroid profiles in ovarian follicular fluid from regularly menstruating women and women after ovarian stimulation
- 2009
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 55:3, s. 519-526
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Journal article (peer-reviewed)abstract
- BACKGROUND: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA). METHODS: We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-microL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups. RESULTS: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013). CONCLUSIONS: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.
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| 22. |
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| 23. |
- Lennartsson, Anna-Karin, et al.
(author)
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Changes in DHEA-s levels during the first year of treatment in patients with clinical burnout are related to health development
- 2016
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In: Biological Psychology. - : Elsevier BV. - 0301-0511 .- 1873-6246. ; 120, s. 28-34
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Journal article (peer-reviewed)abstract
- The regenerative hormone DHEA-S was measured in 122 patients with clinical burnout during their first year of treatment. Relations between change of DHEA-S levels and development in health were investigated. About half of the patients exhibited increased DHEA-S levels during the year, while the other half exhibited decreased levels. There was no difference in burnout symptoms or associated health status at baseline between subsequent DHEA-S increasing and DHEA-S decreasing groups. Greater reduction in the burnout symptoms was observed in patients in who DHEA-S levels increased during the year, than in the patients in who DHEA-S levels decreased. Relative change of DHEA-S and direction of the change during the year both predicted burnout symptoms at the end of the year. In addition, patients with increased DHEA-S levels had better self-rated health, vitality and well-being. Our data suggest that changes in DHEA-S are associated with prognosis for the outcome in burnout patients.
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| 24. |
- Lennartsson, Anna-Karin, et al.
(author)
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Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:10
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Journal article (peer-reviewed)abstract
- ObjectiveDehydroepiandrosterone sulphate (DHEA-s) is an anabolic protective hormone of importance for maintenance of health. DHEA-s levels peak in young adults and decline thereafter with age. DHEA-s has previously been shown to be lower in individuals reporting prolonged stress. This study investigates DHEA-s levels in patients with clinical burnout, a disorder caused by long-term psychosocial stress.Methods122 patients (51% men) and 47 controls (51% men) in the age 25-54 years were included in the study. DHEA-s levels were compared between patients and controls in the whole sample and within each of the three 10-year-interval age groups.ResultsIn the youngest age group (25-34 years), DHEA-s levels were on average 25% lower in the patients (p = 0.006). The differences in DHEA-s levels between patients and controls were more pronounced among female than male participants (on average 32% and 13% lower, respectively). There were no differences in DHEA-s levels between patients and controls in the age group 35-44 years (p = 0.927) or 45-54 years (p = 0.897) or when analyzing all age groups together (p = 0.187).ConclusionThe study indicates that levels of the health promoting "youth" hormone DHEA-s are low in younger burnout patients. The fact that younger adults have much higher DHEA-s levels and more pronounced inter-subject variability in DHEA-s levels than older individuals might explain why burnout status differentiates patients from controls only among the youngest patients included in this study.
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| 25. |
- Lind, Thomas, Docent, 1965-, et al.
(author)
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Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only
- 2019
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In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 177
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Journal article (peer-reviewed)abstract
- Background: Developmental exposure to low doses of the endocrine disruptor bisphenol A (BPA) is known to alter bone tissue in young rodents, although how bone tissue is affected in aged animals is not well known. We have recently shown that low-dose developmental exposure to BPA increases procollagen type I N-terminal propeptide (P1NP) levels, a peptide formed during type 1 collagen synthesis, in plasma of 5-week-old female rat offspring while male offspring showed reduced bone size.Objective: To analyze offspring bone phenotype at 52 weeks of age and clarify whether the BPA-induced increase in P1NP levels at 5 weeks is an early sign of bone marrow fibrosis development.Methods: As in our 5-week study, pregnant Fischer 344 rats were exposed to BPA via drinking water corresponding to 0.5 mu g/kg BW/day (BPA0.5), which is in the range of human daily exposure, or 50 mu g/kg BW/day (BPA50) from gestational day 3.5 until postnatal day 22. Controls were given only vehicle. The offspring were sacrificed at 52 weeks of age. Bone effects were analyzed using peripheral quantitative and micro-computed tomography (microCT), 3-point bending test, plasma markers and histological examination.Results: Compared to a smaller bone size at 5 weeks, at the age of 52 weeks, femur size in male offspring had been normalized in developmentally BPA-exposed rats. The 52-week-old female offspring showed, like the 5-week-old siblings, higher plasma P1NP levels compared to controls but no general increasing bone growth or strength. However, 2 out of 14 BPA-exposed female offspring bones developed extremely thick cortices later in life, discovered by systematic in vivo microCT scanning during the study. This was not observed in male offspring or in female controls. Biomechanical testing revealed that both doses of developmental BPA exposure reduced femur stiffness only in female offspring. In addition, histological analysis showed an increased number of fibrotic lesions only in the bone man ow of female rat offspring developmentally exposed to BPA. In line with this, plasma markers of inflammation, Tnf (in BPA0.5) and Timpl (in BPA50) were increased exclusively in female offspring.Conclusions: Developmental BPA exposure at an environmentally relevant concentration resulted in female specific effects on bone as well as on plasma biomarkers of collagen synthesis and inflammation. Even a dose approximately eight times lower than the current temporary EFSA human tolerable daily intake of 4 mu g/kg BW/day, appeared to induce bone stiffness reduction, bone man ow fibrosis and chronic inflammation in female rat offspring later in life.
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| 26. |
- Naessén, Tord, et al.
(author)
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Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women
- 2010
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:4, s. 1889-1897
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Journal article (peer-reviewed)abstract
- CONTEXT: There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly. OBJECTIVE: The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry. SETTING: The study was conducted at a university hospital research unit. DESIGN AND METHODS: Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded. RESULTS: Men without prevalent CVD had higher plasma 17beta-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06-0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25-0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis. CONCLUSIONS: Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.
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| 27. |
- Naessén, Tord, et al.
(author)
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Higher endogenous estrogen levels in 70-year-old women and men : an endogenous response to counteract developing atherosclerosis?
- 2012
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In: Menopause. - : Ovid Technologies (Wolters Kluwer Health). - 1072-3714 .- 1530-0374. ; 19:12, s. 1322-1328
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Reported associations between endogenous steroid hormone levels and cardiovascular disease in the older population have been contradictory. We evaluated plasma steroid concentrations in terms of the dimensions of the common carotid artery wall layers as a measure of the extent of atherosclerosis.METHODS:A subgroup of 70-year-old participants (32 women and 50 men) from the Prospective Investigation of the Vasculature in Uppsala Seniors study was investigated. All participants had assessments of common carotid artery wall layer parameters (intima thickness, media thickness, and intima-media thickness [IMT] ratio; measured by high-frequency ultrasound at 22 MHz) and endogenous steroid hormone concentrations (measured by liquid chromatography-tandem mass spectrometry).RESULTS:Low androgen levels, high aromatase enzyme activity (estrone [E1]/androstenedione and estradiol [E2]/testosterone), high E2/E1 ratio, and high estrogen levels (E1, E2, estriol, and E2/sex hormone-binding globulin) were consistently associated (often significantly) with a more unhealthy artery wall (thick intima, thin media, and high IMT ratio) in both sexes. Consistently strong associations were found between the aromatase index E2/testosterone and intima, media, and the IMT ratio. For IMT ratio, in both men (rs = 0.52) and women (rs = 0.58), P was <0.001 for both and remained significant after adjustment for cardiovascular disease risk factors and the Framingham risk score (both P < 0.01).CONCLUSIONS:Low androgens, high aromatase enzyme activity, and high estrogen levels are often significantly associated with an unhealthy artery wall on ultrasound. We suggest that the steroid hormone profile of older individuals with higher estrogens most probably reflects an endogenous response to developing atherosclerosis, rather than a cause-and-effect relationship. However, the reverse causality cannot be excluded.
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| 28. |
- Naessén, Tord, et al.
(author)
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Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry.
- 2010
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In: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 94:6, s. 2228-2233
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Journal article (peer-reviewed)abstract
- OBJECTIVE To compare steroid concentrations and steroid product-to-precursor ratios in ovarian follicular fluid (FF) from women with polycystic ovary syndrome (PCOS) and from regularly menstruating women in their early follicular phase, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polycystic ovary syndrome involves abnormal regulation of the steroidogenic enzymes, leading to arrest of follicle development. DESIGN Case-control study. SETTING University hospital clinic. PATIENT(S) Follicular fluid from size-matched ovarian follicles (5-8 mm) in 27 nonstimulated women with PCOS and in 21 women without PCOS was sampled. Thirteen steroids were quantitated from 40 muL of FF, using LC-MS/MS. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Concentrations of steroids in the FF and product-to-precursor ratios (enzyme activity) were compared between the groups. RESULT(S) In women with PCOS, ovarian FF contained higher concentrations of individual and total androgens, lower individual and total estrogens (E), and a lower total E-to-androgen ratio, compared with regularly menstruating women. The product-to-precursor concentration ratios indicated higher CYP17-linked and lower CYP19-linked (aromatase) enzyme activity. Receiver operating characteristic plots indicated the early CYP17 step (17-OH5P/5P) being highly important for the prevalence of PCOS (c = 0.95). CONCLUSION(S) The women with PCOS had higher ovarian CYP17-linked and lower CYP19-linked (aromatase) enzyme activity, confirming previous data. Multiple steroid assessments from minute volumes including FF from nonstimulated ovaries, using LC-MS/MS, might be useful in research, clinical endocrinology, and in IVF.
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| 29. |
- Penell, Johanna Christina, et al.
(author)
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Concentrations of nine endogenous steroid hormones in 70-year-old men and women
- 2021
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In: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 10:5, s. 511-520
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Journal article (peer-reviewed)abstract
- ObjectivesCirculating concentrations of endogenous steroids have systemic implications on health in elderly. However, population-based age- and ethnicity-specific data are scarce. The aim was to report sex-specific plasma concentrations of endogenous sex and adrenal steroids in elderly Swedish Caucasians, to examine the impact of BMI and to present concentrations in apparently healthy subjects.MethodsA population-based observational study of 70-year olds, including 684 community-dwelling men and women enrolled in the PIVUS study, Sweden. Median plasma concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for pregnenolone, 17-hydroxypregnenolone, 17-hydroxy-progesterone, 11-deoxycortisol, DHEA, androstenedione, testosterone, estrone and estradiol.ResultsPlasma concentrations were significantly higher in men (n = 452) than in women (n = 232) for estradiol: median 61.3 pmol/L (95% CI, 11.4, 142.7) vs 18.4 (4.0, 127.3), for estrone: 92.8 (33.3, 206) vs 71.6 (17.8, 209) pmol/L, and for testosterone 13.8 (5.7, 28.0) vs 0.7 (0.2, 2.0) nmol/L. Higher concentrations of estrone and estradiol were observed in obese than non-obese women. Compared to non-obese men, obese men had lower concentrations of testosterone and its precursors: 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione and DHEA. The subgroup of apparently healthy individuals had median values > 20% lower for estrone and estradiol in women but slightly higher for testosterone in both sexes.ConclusionsConcentrations of estradiol, estrone and testosterone were higher in 70-year-old men than in women. BMI associated positively to estradiol and estrone in women and negatively to testosterone in men. Apparently healthy women had lower median concentrations of estradiol and estrone and men had higher median testosterone compared to all individuals.
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| 30. |
- Spörndly-Nees, Ellinor, et al.
(author)
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Low-dose exposure to Bisphenol A during development has limited effects on male reproduction in midpubertal and aging Fischer 344 rats.
- 2018
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 81, s. 196-206
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Journal article (peer-reviewed)abstract
- Low doses of Bisphenol A (BPA) during development may affect reproduction. In this study, Fischer 344 rats were exposed to 0.5 or 50 μg BPA/kg bw/day via drinking water from gestational day 3.5 to postnatal day 22. Anogenital distance, organ weight, histopathology of reproductive organs, hormone analysis and sperm morphology were evaluated in male offspring. In this study no major effects of BPA on male reproduction in midpubertal (postnatal day 35) or adult (12-month-old) rats were revealed, apart from a higher prevalence of mild inflammatory cell infiltrate in cauda epididymis in adult rats exposed to 50 μg BPA/kg bw/day. No BPA-related effects on sexual development were seen but care should be taken when evaluating histopathology in midpuberty testis due to large morphological variation. Results from the present study show no major signs of altered male reproduction in rats exposed to low doses of BPA during gestation and lactation.
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| 31. |
- Ström Holst, Bodil, et al.
(author)
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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for analysis of endogenous steroids in the luteal phase and early pregnancy in dogs : a pilot study
- 2015
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In: Veterinary clinical pathology. - : Wiley. - 0275-6382 .- 1939-165X. ; 44:4, s. 552-558
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Journal article (peer-reviewed)abstract
- Background Blood samples from dogs are often limited in volume, only allowing few steroids to be quantified with immunoassays. In addition, immunoassays may be compromised by interferences such as anti-reagent antibodies. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be used for the simultaneous quantitation of several steroids. This has not been described in dogs before. Objectives The aims were to use LC-MS/MS to study steroid profiles in early pregnancy and luteal phase in dogs, and to determine if differences exist between pregnant (P) and nonpregnant (NP) dogs. Methods Nine female dogs were included, 4 during a NP luteal phase, 4 during a P luteal phase, and one during one NP and one P luteal phase. Blood samples were collected around the time of the LH surge (Day 0) and on Day 26. Serum was analyzed for 5 classes of steroids, including glucocorticoids, androgens, estrogens, pregnanes, and progestins, using LC-MS/MS methods. Results The concentration of progesterone was significantly higher on Day 26 in P than in NP bitches. Distribution of concentrations of glucocorticoids, androgens, estrogens, or pregnanes in P and NP dogs were not statistically different. The predominating glucocorticoid was cortisol, and dihydroepiandrosterone (DHEA) was the predominating androgen. Concentration of estrone was comparable to oestradiol, whereas concentrations of pregnenolone were higher than those of 17-OH pregnenolone. Conclusions Only concentration of progesterone differed between P and NP bitches, being significantly higher on Day 26 in P than in NP bitches. LC-MS/MS offers interesting possibilities for studies of canine reproductive endocrinology.
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| 32. |
- Söndergaard, Hans Peter, et al.
(author)
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Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress
- 2012
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In: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 5:186
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Journal article (peer-reviewed)abstract
- BACKGROUNDDuring the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as; factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome.METHODSEleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children.RESULTS Cortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone) and 17-OH-progesterone were increased in the symptomatic state and decreased after the recovery.CONCLUSIONS Pattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites such as pregnanes and 17-OH-progesterone was found to be associated with the symptomatic state.
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