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Sökning: WFRF:(Theodorsson Elvar)

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31.
  • Ström, Jakob O., 1983-, et al. (författare)
  • Effects of high and low 17β-estradiol doses on focal cerebral ischemia : negative results
  • 2013
  • Ingår i: Scientific Reports. - London, United Kingdom : Nature Publishing Group. - 2045-2322. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17β-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.
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32.
  • Ström, Jakob O., 1983-, et al. (författare)
  • Hormesis and female sex hormones
  • 2011
  • Ingår i: Pharmaceuticals. - Basel, Switzerland : MDPIAG. - 1424-8247. ; 4:5, s. 726-740
  • Forskningsöversikt (refereegranskat)abstract
    • Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.
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33.
  • Ström, Jakob O., 1983-, et al. (författare)
  • Male Testosterone Does Not Adapt to the Partner's Menstrual Cycle
  • 2018
  • Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 15:8, s. 1103-1110
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It has not yet been established whether men in heterosexual relationships adapt their hormone levels to their female partner's menstrual cycle to allocate reproductive resources to the period when the female is actually fertile.Aim: This prospective observational study tested the hypothesis that some males have peaks in testosterone or acne (a possible biomarker for androgen activity) near their partners' ovulation, whereas other males display the opposite pattern.Methods: 48 couples supplied menstrual cycle data, male salivary samples, and a protocol of daily activities for 120 days. Daily saliva samples were analyzed for testosterone concentrations by enzyme-linked immunosorbent assay. The main hypothesis was tested by analyzing whether each individual male's testosterone/acne response to ovulation (either an increase or a decrease in comparison to the individual's average levels) was stable over time. To do this, we analyzed the Spearman correlation between individually normalized periovulatory testosterone and acne during the first half of the study versus the second half of the study.Outcomes: Correlation between each male individual's periovulatory testosterone and acne patterns during the first half of the study versus the second half of the study.Results: No predictability in the male individuals' testosterone (Spearman's rho = -0.018, P = .905) or acne (Spearman's rho = -0.036, P = .862) levels during ovulation was found.Clinical translation: The study being "negative," there is no obvious translational potential in the results.Strengths and limitations: The main strength of this study lies in the excellent compliance of the study participants and the large number of sampling timepoints over several menstrual cycles, thereby allowing each male individual to be his own control subject. A limitation is that samples were only obtained in the morning; however, including later timepoints would have introduced a number of confounders and would also have hampered the study's feasibility.Conclusions: The current results strongly indicate that male morning testosterone levels neither increase nor decrease in response to the partner's ovulation. This discordance to previous laboratory studies could indicate either that (i) the phenomenon of hormonal adaptation of men to women does not exist and earlier experimental studies should be questioned, (ii) that the phenomenon is short-lived/acute and wanes if the exposure is sustained, or (iii) that the male testosterone response may be directed toward other women than the partner. Copyright (C) 2018, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.
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34.
  • Ström, Jakob O., 1983-, et al. (författare)
  • Order of magnitude differences between methods for maintaining physiological 17beta-oestradiol concentrations in ovariectomized rats
  • 2008
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Oslo, Norway : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 68:8, s. 814-822
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of animal models, especially the rat, is crucial for elucidating the biological effects and mechanisms of the widely used hormone 17beta-oestradiol. Unfortunately, there is a lack of consensus on optimal means of obtaining and maintaining physiological 17beta-oestradiol concentrations in plasma and this may be the reason for the varying results in several studies, including the disagreement on whether 17beta-oestradiol is neuroprotective or not. Very few studies have been devoted to investigating the characteristics and biological relevance of different methods of 17beta-oestradiol administration. We therefore ovariectomized 75 Sprague-Dawley rats and, following a 2-week washout period, administered 17beta-oestradiol using three different methods; daily injections (10 microg 17beta-oestradiol/kg), slow-release pellets (0.25 mg 60 day-release pellets, 0.10 mg 90 day-release pellets) and silastic capsules (with/without washout periods) (silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with 20 mm columns of 180 microg 17beta-oestradiol/mL sesame oil). A further 45 animals were used as ovariectomized and native controls studied in different parts of the oestrous cycle. Silastic capsules produced concentrations of 17beta-oestradiol within the physiological range 4-5 weeks independently of whether a prior washout period was included or not. The slow-release pellets, irrespective of dose or release period, resulted in initial concentrations an order of magnitude above physiological concentrations during the first 2 weeks followed by a substantial decrease. Daily injections resulted in increasing 17beta-oestradiol concentrations, but within physiological levels. Silastic capsules are conveniently manufactured and used and are superior to pellets and injections in reliably producing long-term 17beta-oestradiol concentrations within the physiological range.
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35.
  • Ström, Jakob O., et al. (författare)
  • Order of magnitude differences between methods for maintaining physiological 17β-estradiol concentrations in ovariectomized rats
  • 2008
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 68:8, s. 814-822
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of animal, especially rat, models, is crucial for elucidating the biological effects and mechanisms of the widely used hormone 17β-estradiol. Unfortunately there is a lack of consensus on optimal means of obtaining and maintaining physiological 17β-estradiol concentrations in plasma. This may be the reason for varying results in several studies including the disagreement on whether 17β-estradiol is neuroprotective or not. Very few studies have been devoted to investigating the characteristics and biological relevance of different methods of 17β-estradiol administration. We therefore ovariectomized 75 Sprague-Dawley rats and, following a 2 weeks wash-out period, administered 17β-estradiol using three different methods; daily injections (10 µg 17β-estradiol/kg), slow-release pellets (0.25 mg 60 day-release pellets, 0.10 mg 90 day-release pellets) and silastic capsules (with/without wash-out periods) (silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with 20 mm columns of 180 µg 17β-estradiol/mL sesame oil). Further 45 animals were used as ovariectomized and native controls, studied in different parts of the estrous cycle. Silastic capsules produced concentrations of 17β-estradiol within the physiological range for 4-5 weeks independent of whether a prior wash-out period was included or not. The slow-release pellets, irrespective of dose or release period, resulted in initial concentrations which were an order of magnitude above physiological concentrations during the first two weeks followed by a substantial decrease. Daily injections resulted in increasing 17β-estradiol concentrations, however within physiological levels. Silastic capsules are conveniently manufactured and used, and are superior to pellets and injections in reliably producing long-term 17β-estradiol concentrations within the physiological range.
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36.
  • Ström, Jakob O., 1983-, et al. (författare)
  • Ovariectomy and 17β-estradiol replacement in rats and mice : a visual demonstration
  • 2012
  • Ingår i: Journal of Visualized Experiments. - Cambridge, USA : Journal of Visualized Experiments. - 1940-087X. ; :64
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.
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37.
  • Ström, Jakob O., et al. (författare)
  • Substantial discrepancies in 17β-estradiol concentrations obtained with three different commercial direct radioimmunoassay kits in rat sera
  • 2008
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Oslo, Norway : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 68:8, s. 806-813
  • Tidskriftsartikel (refereegranskat)abstract
    • The extensive use of estrogen for contraception and amelioration of post-menopausal symptoms has made it the subject of substantial recent research efforts. Ovariectomized (ovx) rats treated with exogenous ovarial hormones constitute important tools in the investigation of the effects and mechanisms of estrogen actions. The crucial need to control and to monitor plasma levels of 17β-estradiol calls for accurate, precise and robust assay methods. The performance of direct radioimmunoassays (RIAs) for measurement of 17β-estradiol has previously been reported for human samples, but – to our knowledge – not for rat samples. In the current study, 552 serum samples from ovx, native and hormone treated rats were used to compare the performance of three commercially manufactured direct RIAs from the companies DPC (Siemens Healthcare Diagnostics Inc., formerly Diagnostic Products Corporation), DSL (Diagnostic Systems Labs) and MPB (MP Biomedicals, formerly ICN Biomedicals). Substantial differences in results between the three assay methods were found when measuring serum 17β-estradiol concentrations. The following formulas, describing the relation between the different methods’ results, were obtained using weighted Deming’s orthogonal regression (all regression formulae in the abstract are based on pg/mL): DSL= 0.43*DPC+12.3, MPB= 2.1*DPC+84.7 and DSL= 4.8*MPB+22.2. Furthermore, a preceding diethyl ether extraction step of the serum appears to impair the RIAs’ performances in the present samples: DPCex= 0.39*DPCunex+0.76, DSLex= 0.32*DSLunex-1.7 and MPBex= 0.22*MPBunex+1.4.
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38.
  • Ström, Jakob O., 1983-, et al. (författare)
  • The female menstrual cycle does not influence testosterone concentrations in male partners
  • 2012
  • Ingår i: Journal of Negative Results in BioMedicine. - London, United Kingdom : BioMed Central (BMC). - 1477-5751. ; 11, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation.Methods: Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis.Results: In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05).Conclusions: Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.
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39.
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40.
  • Ström, Jakob (författare)
  • The dose-dependent effects of estrogens on ischemic stroke
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Estrogens are a group of female sex hormones that in addition to central roles in reproductive functions also have profound impact on for example brain development, blood vessels, bone tissue, metabolism and the immune system. The dominant endogenous production sites for estrogens in females are the ovaries and adipose tissue, while exogenous sources include combined contraceptive hormone treatments and menopausal hormone therapy. A few decades ago, the observation that females in comparison to men seemed to be protected against cerebral ischemia, and that this benefit was partially lost during menopause, sparked the hypothesis that estrogens protect against stroke. This was later confirmed by epidemiological studies and a large number of experimental animal studies, which motivated extensive clinical trials in which estrogens and/or progestagens were administered with the intent to prevent degenerative conditions rather than to ameliorate menopausal symptoms. However, the results were generally disappointing. The largest study, the Women’s Health Initiative (WHI), was discontinued due to the observation of an increased risk of breast cancer, cardiovascular disease and stroke. In parallel, a small number of animal studies in which estrogens were shown to increase damage from cerebral ischemia were published, one of these originating from our laboratory. This was, despite the WHI outcome, a surprising result, since the vast majority of previous animal studies had demonstrated protective effects.Therefore, in an attempt to explain the discordant results, Paper 1, and later Paper 4, of the current thesis were planned, in which four 17β-estradiol administration methods were tested. Substantial differences in serum hormone concentrations resulted from the different methods. Most importantly, the commercially available slow-release pellets used in our earlier experiments resulted in extremely high serum concentrations of 17β-estradiol. In Paper 2, 66 published studies that had investigated the effects of estrogens on stroke were meta-analyzed to pin-point the methodological reasons for the result dichotomy. Strikingly, in all six studies in which estrogens had produced damaging effects, the same type of slow-release pellets had been used, although these were used in a minority of the total number of studies. Paper 3 substantially strengthened the hypothesis that administration methods were crucial by showing that repeating the earlier experiment from our laboratory in which pellets had been used, but using a low-dose regimen instead, switched the estrogen effects from neurodamaging to neuroprotective. In Paper 5, an effort was made to challenge the assumption that the dose, and not the administration method per se, was the key factor, however this failed due to large intra-group infarct size variability.The current thesis adds evidence to the notion that differences in administration methods and their resulting serum concentrations of 17β-estradiol constitute a major factor responsible for the dichotomous results in studies investigating estrogens’ effects on cerebral ischemia. Even though results from animal studies are difficult to extrapolate to humans, this has a bearing on the menopausal hormone therapy debate, indicating that the risk of stroke could be reduced if serum concentrations of estrogens are minimized.
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