| 1. |
- Islander, Ulrika, 1975, et al.
(författare)
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Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands
- 2005
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Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Estrogens and androgens have extensive effects on the immune system, for example they suppress both T and B lymphopoiesis in thymus and bone marrow. Submandibular glands are sexually dimorphic in rodents, resulting in larger granular convoluted tubules in males compared to females. The aim of the present experiments was to investigate the estrogenic and androgenic effects of 4-estren-3alpha,17beta-diol (estren) on thymus, bone marrow and submandibular glands, and compare the effects to those of 17beta-estradiol (E2) and 5alpha-dihydrotestosterone (DHT), respectively. Estrogen receptors (ERs) were blocked by treatment of mice with the ER-antagonist ICI 182,780; also, knock-out mice lacking one or both ERs were used. RESULTS: As expected, the presence of functional ERs was mandatory for all the effects of E2. Similar to DHT-treatment, estren-treatment resulted in decreased thymus weight, as well as decreased frequency of bone marrow B cells. Treatment with estren or DHT also resulted in a shift in submandibular glands towards an androgen phenotype. All the effects of estren and DHT were independent of ERs. CONCLUSION: Our study is the first to show that estren has similar effects as the androgen DHT on lymphopoiesis in thymus and bone marrow, and on submandibular glands, and that these effects are independent of estrogen receptors. This supports the hypothesis of estren being able to signal through the androgen receptor.
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| 2. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.
- 2006
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381 .- 1930-739X. ; 14:4, s. 662-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men. RESEARCH METHODS AND PROCEDURES: Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. RESULTS: DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production. DISCUSSION: We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.
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| 3. |
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| 4. |
- Chagin, A S, et al.
(författare)
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Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice.
- 2004
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 19:1, s. 72-7
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Tidskriftsartikel (refereegranskat)abstract
- To determine the long-term role of ER beta in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. Our results show that ER beta inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. INTRODUCTION: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER) alpha-/- and the ER alpha-/- beta-/-, but not the ER beta-/-, mouse models have clearly increased serum levels of estradiol. MATERIALS AND METHODS: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. RESULTS: Young adult (4-month-old) ER beta-/- mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER beta inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER alpha-/- mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER alpha-/- mice, must be mediated through ER beta because old ER alpah-/- beta-/- mice displayed unchanged, unfused growth plates. CONCLUSIONS: Our results confirm that ER beta is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER beta, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice.
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| 5. |
- Folkersen, Lasse, et al.
(författare)
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Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease
- 2017
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.
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| 6. |
- Gustafsson, Karin L., 1987, et al.
(författare)
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A tissue-specific role of membrane-initiated ERα signaling for the effects of SERMs
- 2022
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Ingår i: Journal of Endocrinology. - 0022-0795. ; 253:2, s. 75-84
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Tidskriftsartikel (refereegranskat)abstract
- Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. ERs exert effects via nuclear actions but can also utilize membrane-initiated signaling pathways. To dete rmine if membrane-initiated ERα (mERα) signaling affects SERM action in a tissue-specific manner, C451 A mice, lacking mERα signaling due to a mutation at palmitoylation site C451, were treated with Lasofoxifene (Las), Bazedoxifene (Bza), or estradi ol (E2), and various tissues were evaluated. Las and Bza treatment increased uterine weight to a similar extent in C451A and control mice, demonstrating mERα-independent uterine SERM effects, while the E2 effect on the uterus was predominantly mER α-dependent. Las and Bza treatment increased both trabecular and cortical bone mass in controls to a similar degree as E2, while both SERM and E2 treatment effects were abse nt in C451A mice. This demonstrates that SERM effects, similar to E2 effects, in th e skeleton are mERα- dependent. Both Las and E2 treatment decreased thymus weight in controls, while neither treatment affected the thymus in C451A mice, demonstrati ng mERα-dependent SERM and E2 effects in this tissue. Interestingly, both SERM and E2 treatments decreased the total body fat percent in C451A mice, demonstrating the ability of these treatments to affect fat tissue in the absence of functional mER α signaling. In conclusion, mERα signaling can modulate SERM responses in a tissue-specific manne r. This novel knowledge increases the understanding of the mechanisms behind SERM effects and may thereby facilitate the development of new improved SERMs.
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| 7. |
- Gustafsson, Karin L., 1987, et al.
(författare)
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ER alpha expression in T lymphocytes is dispensable for estrogenic effects in bone
- 2018
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 238:2, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERa) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERa expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERa expression specifically in T lymphocytes (Lck-ERa-/-) and ERaflox/flox littermate (control) mice. Deletion of ERa expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERa-/compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERa-/- mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERa-/- led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERa in T lymphocytes. In conclusion, ERa expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.
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| 8. |
- Gustafsson, Sofia, 1975-
(författare)
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Comparability between the Medieval Swedish Town Law and the Lübeck Law
- 2009. - 1
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Ingår i: Crossing Legal Cultures. - München : Martin Meidenbauer. - 9783899751543 ; , s. 129-140
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Mit ihren 34 gesammelten Beitraegen zielt die vorliegende Publikation darauf ab, die Reihe European Yearbook of Young Legal History mit einem anspruchsvollen wissenschaftlichen Grenzbereich zusammenzufuehren. Sie naehert sich der Disziplin der Rechtsgeschichte in einem komplexen Ansatz, indem sie sich ganz bewusst ueber die ungeschriebenen roten Grenzlinien allgemein anerkannter Rechtsgeschichte hinaus begibt, welche bisher von der vorherrschenden Geschichtsschreibung gepraegt ist. Dabei gelingt es dem Band, Disziplinen benachbarter sozialwissenschaftlicher Richtungen, wie beispielsweise die der Linguistik, der Theorie Internationaler Beziehungen, der Geschichte des Altertums und sogar der Roemischen Gesetzgebung aufzugreifen und einzubeziehen. Insofern strebt dieses Projekt danach, zu einem besseren, nicht notgedrungen konfliktgeladenen Verstaendnis der interkulturellen Erzeugung gesetzlicher Praktiken, Mechanismen und Normen in Europa beizutragen.
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| 9. |
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| 10. |
- Gustafsson, Sofia, 1975-
(författare)
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Consulting with the Community in Late Medieval Towns
- 2007
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Ingår i: Urban Europe in Comparative Perspective. - Stockholm : Institute of Urban History, Stockholm University. - 9188882284
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 11. |
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| 12. |
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| 13. |
- Gustafsson, Sofia, 1975-
(författare)
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Governance of northern European towns in the Middle Ages : the benefits of a comparative perspective
- 2011
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Ingår i: La gobernanza de la cuidad europea en la Edad Media. - Logroño : Instituto de Estudios Riojanos. - 9788499600109 ; , s. 47-74
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The essay is about medieval town governance in northern Europe. By comparing English, German and Scandinavian towns, the structural similarities among medieval towns are pointed out. The roles played by the major actors within the towns: town lords, bailiffs, burgomasters, councils and the burgher communities are scrutinized, as well as their relationships to each other and how these changed over the centuries. Even though every medieval town differed from the other depending on their local conditions, a majority of towns shared a common basic structure of governance, irrespective of their geographical location and prerequisites. This is interpreted as being a result of a common town culture. The author therefore encourages wider perspecives, beyond the regional and national sphere, in studies of medieval towns.
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| 14. |
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| 15. |
- Gustafsson, Sofia, Filosofie Doktor, 1975-
(författare)
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Joen Petri Klint : Stridbar kyrkoherde i Vasatid
- 2018
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Ingår i: Personhistorisk Tidskrift. - Johanneshov, Sweden : Personhistoriska Samfundet. - 0031-5699. ; 1:114, s. 29-50
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Gustafsson, Sofia, Filosofie Doktor, 1975-
(författare)
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Järtecken : Joen Petri Klint och 1500-talets vidunderliga lutherdom
- 2018
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Kometer, norrsken, jordbävningar, drakar, missbildningar och andra märkligheter ofta uppfattades de som så kallade järtecken som varslade om kommande olyckor.I sin 400 sidor långa bok från 1500-talets andra hälft beskriver kyrkoherden Joen Petri Klint i ord och bild dessa bisarra tecken, deras uppkomst och betydelser. Han försöker finna sambandet mellan dem och efterföljande händelser såsom Johan III:s död och slaget vid Stångebro. Intresset för järtecken delade Klint med sin omvärld, inte minst med det lutherska prästerskapet i Europa. Naturfenomen betraktades av de flesta som en reaktion från Gud på människornas synder i värsta fall ett tecken på den annalkande apokalypsen.I Järtecken analyserar historikern Sofia Gustafsson Klints tidigare förbisedda järteckenbok i ljuset av tidens lutherska föreställningsvärld. Varför skrev Klint boken och hur typiska var berättelserna i boken för sin tid?
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| 17. |
- Gustafsson, Sofia, Biträdande professor, 1975-
(författare)
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Järteckentro i reformationstid
- 2024
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Ingår i: Nordbor. - Stockholm : Makadam Förlag. - 9789170614705 ; , s. 62-67
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Bokkapitel (populärvet., debatt m.m.)
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| 18. |
- Gustafsson, Sofia, 1975-
(författare)
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Måltid på rådhuset
- 2016
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Ingår i: Biskop Brasks måltider. - Stockholm : Bokförlaget Atlantis. - 9789173538282 ; , s. 161-182
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Gustafsson, Sofia, 1975-
(författare)
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Sale of Goods around the Baltic Sea in the Middle Ages
- 2012
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Ingår i: The Hanse in Medieval and Early Modern Europe. - Leiden : Brill Academic Publishers. - 9789004212527 - 9789004241930 ; , s. 129-148
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Gustafsson, Sofia, 1975-
(författare)
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Succession in Medieval Swedish Town Councils
- 2009. - 1
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Ingår i: Generations in Towns. - Newcastle upon Tyne : Cambridge Scholars Publishing. - 9781443813013 ; , s. 194-209
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The existence and changing of generations in family life, business and politics was a central feature of towns as well as rural societies in earlier times. Even so, it remains understudied by urban historians of the pre-modern period. This book aims to fill some of this gap, containing twelve studies of generations in late medieval and early modern European towns, ranging from the Mediterranean to the Nordic countries, with a time-span from the fourteenth to the early nineteenth century. Dealing with topics like succession and inheritance, family consciousness, as well as relations and conflicts within and between generations, the articles demonstrate the importance and potential of generational studies on pre-modern towns. The book will appeal to anyone who takes an interest in urban social and cultural history, legal and family history in medieval and early modern times.Show more Show less
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| 21. |
- Gustafsson, Sofia, 1975-
(författare)
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Svenska städer i medeltidens Europa : En komparativ studie av stadsorganisation och politisk kultur
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- How did the Swedish towns compare to the surrounding world during the late Middle Ages concerning town organization and political culture? Previous research has claimed a strong German influence on the Swedish town life, but in this dissertation the Europeanization is being put forward as the explanatory factor for the extensive international similarities that can be identified during the Middle Ages. The towns were part of an international town culture that was highly integrated. Differences between towns are foremost analysed as a result of different local conditions such as population size, social structure and relationship to the town lord. Since preserved sources from all towns of medieval Sweden (including Finland) have been examined in a joint study and been placed in a wider context, the dissertation presents renewed and deepened knowledge about the Swedish towns. The study includes Danish, English and German towns and thus compares regions with each other that rarely have been compared before, and thereby presents new perspectives on each respective area. The aspects of the organization that are being systematically compared are the creation of councils, the number of aldermen and mayors, the rotation of offices and functions of the town lords, bailiffs, councils, mayors and chamberlains. Regarding political culture, it is investigated how the councils expressed their group cohesiveness and power in the town and how they defined the border between themselves and the town population. Furthermore, the expectations the town populations placed on the officials and their perception of their own part in the rule of the town is being examined. Finally, the political interaction between council and town population in different towns is compared and analysed.
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| 22. |
- Gustafsson, Sofia, 1975-
(författare)
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Tecken i skyn
- 2010
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Ingår i: Sveriges historia 1350-1600. - Stockholm : Norstedts. ; , s. 372-377
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Bokkapitel (populärvet., debatt m.m.)
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| 23. |
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| 24. |
- Gustafsson, Sofia, Biträdande professor, 1975-
(författare)
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The legal position of guests in late medieval Stockholm
- 2024
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Ingår i: Urban History. - : Cambridge University Press. - 0963-9268 .- 1469-8706.
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Tidskriftsartikel (refereegranskat)abstract
- The article analyses the legal position of foreign visitors in late medieval Stockholm through the prism of the concept of legal certainty, which requires public, explicit and clear regulations, an institutionalized jurisdiction and equal, just and impartial judgments in court. The article concludes that the authorities in Stockholm strove to create legal certainty for foreign guests and that the regulated relationship between local hosts and visiting guests both provided a control mechanism for the authorities and security for the guests.
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| 25. |
- Islander, Ulrika, 1975, et al.
(författare)
-
Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent
- 2005
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Ingår i: Clin Exp Immunol. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 139:2, s. 210-5
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen has extensive effects on the immune system. The aim of the present experiments was to compare the effects of 17beta-estradiol (E2) and 4-estren-3alpha,17beta-diol (estren) on T lymphopoiesis and T cell-dependent inflammation. In order to investigate the role of estrogen receptors (ER) in the effects of E2 and estren on the immune system, ER knock-out mice lacking both ERalpha and ERbeta (DERKO) were used. T lymphopoiesis and T cell-dependent inflammation were studied by investigating thymus cellularity, the delayed-type hypersensitivity (DTH) reaction, CD4(+) T cells in spleen and serum levels of interleukin (IL)-6. As expected, the presence of ERs was mandatory for all the effects of E2. In contrast, treatment with estren reduced thymus cellularity in ER knock-out mice, indicating an effect through ER-independent pathways. Interestingly, estren suppressed only DTH, the frequency of CD4(+) T cells in spleen and serum levels of IL-6 in wild-type (WT) mice, but not in mice lacking ERs. Thus, our study is the first to show that estren inhibits T lymphopoiesis via ER-independent pathways, whereas its suppressive effects on inflammation are ER-dependent.
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| 26. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice.
- 2003
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 17:2, s. 203-8
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-beta (ERbeta) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERbeta-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERbeta-inactivated than in WT mice, demonstrating that ERbeta reduces estrogen receptor-alpha (ERalpha)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERalpha-inactivated mice was intermediate between that seen in WT and ERalphabeta double-inactivated mice. Thus, ERbeta inhibits ERalpha-mediated gene transcription in the presence of ERalpha, whereas, in the absence of ERalpha, it can partially replace ERalpha. In conclusion, our in vivo data indicate that an important physiological role of ERbeta is to modulate ERalpha-mediated gene transcription supporting a "Ying Yang" relationship between ERalpha and ERbeta in mice.
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| 27. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Estrogen receptor specificity for the effects of estrogen in ovariectomized mice.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 174:2, s. 167-78
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen exerts a variety of important physiological effects, which have been suggested to be mediated via the two known estrogen receptors (ERs), alpha and beta. Three-month-old ovariectomized mice, lacking one or both of the two estrogen receptors, were given estrogen subcutaneously (2.3 micro g/mouse per day) and the effects on different estrogen-responsive parameters, including skeletal effects, were studied. We found that estrogen increased the cortical bone dimensions in both wild-type (WT) and double ER knockout (DERKO) mice. DNA microarray analysis was performed to characterize this effect on cortical bone and it identified four genes that were regulated by estrogen in both WT and DERKO mice. The effect of estrogen on cortical bone in DERKO mice might either be due to remaining ERalpha activity or represent an ERalpha/ERbeta-independent effect. Other effects of estrogen, such as increased trabecular bone mineral density, thymic atrophy, fat reduction and increased uterine weight, were mainly ERalpha mediated.
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| 28. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Identification of estrogen-regulated genes of potential importance for the regulation of trabecular bone mineral density.
- 2002
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 17:12, s. 2183-95
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen is of importance for the regulation of trabecular bone mineral density (BMD). The aim of this study was to search for possible mechanisms of action of estrogen on bone. Ovariectomized (OVX) mice were treated with 17beta-estradiol. Possible effects of estrogen on the expression of 125 different bone-related genes in humerus were analyzed using the microarray technique. Estrogen regulated 12 of these genes, namely, two growth factor-related genes, 8 cytokines, and 2 bone matrix-related genes. Five of the 12 genes are known to be estrogen-regulated, and the remaining 7 genes are novel estrogen-regulated genes. Seven genes, including interleukin-1 receptor antagonist (IL-1ra), IL-1receptor type II (IL-1RII), insulin-like growth factor-binding protein 4 (IGFBP-4), transforming growth factor beta (TGF-beta), granulocyte colony-stimulating factor receptor (G-CSFR), leukemia inhibitory factor receptor (LIFR), and soluble IL-4 receptor (sIL-4R) were selected as probable candidate genes for the trabecular bone-sparing effect of estrogen, as the mRNA levels of these genes were highly correlated (r2 > 0.65) to the trabecular BMD. The regulation of most of these seven genes was predominantly estrogen receptor alpha (ER-alpha)-mediated (5/7) while some genes (2/7) were regulated both via ER-alpha and ER-beta. In conclusion, by using the microarray technique, we have identified four previously known and three novel estrogen-regulated genes of potential importance for the trabecular bone-sparing effect of estrogen.
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| 29. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Two different pathways for the maintenance of trabecular bone in adult male mice.
- 2002
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 17:4, s. 555-62
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Tidskriftsartikel (refereegranskat)abstract
- Androgens may regulate the male skeleton either directly via activation of the androgen receptor (AR) or indirectly via aromatization of androgens into estrogen and, thereafter, via activation of estrogen receptors (ERs). There are two known estrogen receptors, ER-alpha and ER-beta. The aim of this study was to investigate the relative roles of ER-alpha, ER-beta, and AR in the maintenance of trabecular bone in male mice. Seven-month-old male mice, lacking ER-alpha (ERKO), ER-beta (BERKO), or both receptors (DERKO), were orchidectomized (orx) and treated for 3 weeks with 0.7 microg/mouse per day of 17beta-estradiol or vehicle. No reduction in trabecular bone mineral density (BMD) was seen in ERKO, BERKO, or DERKO mice before orx, showing that neither ER-a nor ER-beta is required for the maintenance of a normal trabecular BMD in male mice. After orx, there was a pronounced decrease in trabecular BMD, similar for all groups, resulting in equal levels of trabecular BMD in all genotypes. This reduction was reversed completely in wild-type (WT) and BERKO mice treated with estrogen, and no significant effect of estrogen was found in ERKO or DERKO mice. In summary, the trabecular bone is preserved both by a testicular factor, presumably testosterone acting via AR and by an estrogen-induced activation of ER-alpha. These results indicate that AR and ER-alpha are redundant in the maintenance of the trabecular bone in male mice. In contrast, ER-beta is of no importance for the regulation of trabecular bone in male mice.
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| 30. |
- Movérare, Sofia, et al.
(författare)
-
Estren is a selective estrogen receptor modulator with transcriptional activity.
- 2003
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Ingår i: Molecular pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0026-895X .- 1521-0111. ; 64:6, s. 1428-33
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Tidskriftsartikel (refereegranskat)abstract
- It was recently reported that the synthetic compound estren increases bone mass without affecting reproductive organs or classic transcription. The aim of the present study was to further characterize the in vivo and in vitro effects of estren. We demonstrate that estren is a selective estrogen receptor modulator (SERM) with a strong effect on thymus, a moderate effect on uterus and trabecular bone, but no major effect on fat or cortical bone in 11-month-old ovariectomized mice. The effect of estren on trabecular bone and uterus is mediated via estrogen receptors (ERs) because no effect is seen in ER double-inactivated mice. Furthermore, with the use of ERalpha- and ERbeta-expressing reporter cell lines, we demonstrate that estren displays an agonistic effect on transcriptional activity of an estrogen-responsive element-driven reporter gene with a degree of agonism similar to that of 17beta-estradiol for both ERalpha and ERbeta. Thus, estren has the capacity to exert genomic effects via both ERalpha and ERbeta. We conclude, in contrast to what was previously reported by others, that estren is a SERM with transcriptional activity.
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| 31. |
- Movérare, Sofia, et al.
(författare)
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Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the hair follicle cycling as well as the thickness of epidermis in male mice.
- 2002
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 0022-202X. ; 119:5, s. 1053-8
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen is of importance for the regulation of hair growth and epidermal thickness. The effects of estrogen have predominantly been studied in females; however, recent studies demonstrate that estrogen also is critical for males. The aim of this study was to investigate the relative functional importance of estrogen receptor alpha and estrogen receptor beta in the regulation of the hair follicle cycling and epidermal thickness in male mice. Seven month old transgenic male mice, lacking estrogen receptor alpha (ERKO), estrogen receptor beta (BERKO), or both receptors (DERKO), were orchidectomized and treated for 3 week with 17beta-estradiol or vehicle. Orchidectomy induced a synchronized anagen phase of the hair follicles, which was inhibited by 17beta-estradiol treatment in wild-type and BERKO mice, but not in ERKO and DERKO mice. Furthermore, 17beta-estradiol treatment increased the thickness of epidermis in wild-type and BERKO mice, but not in ERKO and DERKO. This study demonstrates that estrogen is of importance for the regulation of hair follicle cycling and epidermal thickness in male mice. The effect on hair follicle cycling is caused by an estrogen receptor alpha mediated inhibition of telogen-anagen transition and the effect of estrogen to increase epidermal thickness is associated with an estrogen receptor alpha mediated increase in the proliferative rate of the keratinocytes in the basal cell layer of the epidermis.
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| 32. |
- Ng, Nawi, 1974, et al.
(författare)
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Sustainable Behavior Change for Health Supported by Person-Tailored, Adaptive, Risk-Aware Digital Coaching in a Social Context: Study Protocol for the STAR-C Research Programme
- 2021
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Vasterbotten Intervention Programme (VIP) in the Region Vasterbotten Sweden is one of the very few cardiovascular disease (CVD) prevention programmes globally that is integrated into routine primary health care. The VIP has been shown as a cost-effective intervention to significantly reduce CVD mortality. However, little is known about the effectiveness of a digital solution to tailor risk communication strategies for supporting behavioral change. STAR-C aims to develop and evaluate a technical platform for personalized digital coaching that will support behavioral change aimed at preventing CVD. Methods: STAR-C employs a mixed-methods design in seven multidisciplinary projects, which runs in two phases during 2019-2024: (i) a formative intervention design and development phase, and (ii) an intervention implementation and evaluation phase. In the 1st phase, STAR-C will model the trajectories of health behaviors and their impact on CVDs (Project 1), evaluate the role of the social environment and social networks on behavioral change (Project 2) and assess whether and how social media facilitates the spread of health information beyond targeted individuals and stimulates public engagement in health promotion (Project 3). The findings will be utilized in carrying out the iterative, user-centered design, and development of a person-tailored digital coaching platform (Project 4). In the 2nd phase, STAR-C will evaluate the implementation of the coaching programme and its effectiveness for promoting behavioral change and the spreading of health information across social networks and via social media (Project 5). The cost-effectiveness (Project 6) and ethical issues (Project 7) related to the coaching programme intervention will be evaluated. Discussion: The STAR-C research programme will address the knowledge and practice research gaps in the use of information technologies in health promotion and non-communicable disease (NCD) prevention programmes in order to narrow the health inequality gaps. Ethics: STAR-C has received approval from the Swedish Ethical Review Authority (Dnr. 2019-02924;2020-02985). Dissemination: The collaboration between Umea University and Region Vasterbotten will ensure the feasibility of STAR-C in the service delivery context. Results will be communicated with decision-makers at different levels of society, stakeholders from other regions and healthcare professional organizations, and through NGOs, local and social media platforms.
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| 33. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Mild stimulatory effect of a probiotic mix on bone mass when treatment is initiated 1.5 weeks after ovariectomy in mice
- 2021
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 320:3
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Tidskriftsartikel (refereegranskat)abstract
- Studies in humans and rodents show that probiotic bacteria can protect from bone loss caused by sex steroid deficiency. We showed earlier that a mixture of three probiotic bacteria, Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312, and DSM 15313 (L. mix), protects mice from ovariectomy (ovx)-induced bone loss when treatment was started 2 wk before sham and ovx surgery. In addition, the same probiotic treatment protected against lumbar spine bone loss in early postmenopausal women. In the present study, we wanted to evaluate the therapeutic potential of L. mix by starting treatment 1.5 wk after ovx when most of the rapid bone loss as a result of estrogen deficiency has already occurred. Treatment with L. mix for 5.5 wk increased the trabecular thickness but not the trabecular number in the proximal metaphyseal region of tibia compared with vehicle treatment. Cortical thickness and cortical area of the middiaphyseal part of the tibia were significantly decreased in ovx mice but not in L. mix-treated ovx mice. The bone-protective effects of L. mix in ovx mice were associated with a protection against ovx-induced reduction of the frequency of regulatory T-cells and of the expression of Tgfb in the bone marrow. In conclusion, the probiotic L. mix exerted a mild stimulatory effect on trabecular and cortical bone width when treatment is initiated 1.5 wk after ovariectomy in mice. This effect was associated with effects on bone-protecting regulatory T-cells. The results suggest that L. mix may exert beneficial effects on bone mass when treatment is started after ovariectomy. NEW & NOTEWORTHY The probiotic L. mix exerted a mild stimulatory effect on trabecular and cortical bone width when treatment is initiated 1.5 wk after ovariectomy in mice. This effect was associated with effects on bone-protecting regulatory T-cells. The results suggest that L. mix may exert beneficial effects on bone mass when treatment is started after ovariectomy.
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| 34. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Phosphorylation site S122 in estrogen receptor α has a tissue-dependent role in female mice
- 2020
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Ingår i: FASEB Journal. - 0892-6638 .- 1530-6860. ; 34, s. 15991-16002
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen treatment increases bone mass and reduces fat mass but is associated with adverse effects in postmenopausal women. Knowledge regarding tissue-specific estrogen signaling is important to aid the development of new tissue-specific treatments. We hypothesized that the posttranslational modification phosphorylation in estrogen receptor alpha (ERα) may modulate ERα activity in a tissue-dependent manner. Phosphorylation of site S122 in ERα has been shown in vitro to affect ERα activity, but the tissue-specific role in vivo is unknown. We herein developed and phenotyped a novel mouse model with a point mutation at the phosphorylation site 122 in ERα (S122A). Female S122A mice had increased fat mass and serum insulin levels but unchanged serum sex steroid levels, uterus weight, bone mass, thymus weight, and lymphocyte maturation compared to WT mice. In conclusion, phosphorylation site S122 in ERα has a tissue-dependent role with an impact specifically on fat mass in female mice. This study is the first to demonstrate in vivo that a phosphorylation site in a transactivation domain in a nuclear steroid receptor modulates the receptor activity in a tissue-dependent manner.
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| 35. |
- Petersson, Erik, 1985-
(författare)
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Vadstena krigsmanshus : En studie av den svenska kronans inrättning för sårade och gamla soldater cirka 1640–1780
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Den här avhandlingen handlar det underhåll till sårade och gamla soldater som den svenskastatsmakten organiserade under tidigmodern tid. Undersökningen tar sin utgångspunkt i den tid närstatsmakten började organisera mer omfattande hjälp för soldater, vilket var slutet på Gustav Vasasoch under Erik XIV:s regeringstid i mitten av 1500-talet. Motiven till att statsmakten organiseradehjälp för en del soldater var att dessa skulle ha offrat sin hälsa och arbetsförmåga i kronans tjänst, menså länge statsmakten fortsatte att vara relativt löst organiserad var även hjälpen till soldaterna avganska liten omfattning. Det ändrades under Gustav II Adolfs regering då planerna på att skapa ettkrigsmanshus i Vadstena etablerades, vilka senare genomfördes efter hans död och institutionen kundeta emot de första soldaterna senast 1640. I krigsmanshuset fick ett trettiotal soldater med familjeruppehälle, samtidigt som soldater boende i andra delar av landet fick stöd från krigsmanshuskassansom också administrerades från Vadstena. Mot slutet av 1600-talet blev kassan proportionellt merbetydelsefull än krigsmanshuset och runt år 1700 försörjde kassan flera tusen soldater runtom i riket.1700-talet innebar stora förändringar, bland annat genom att krigen blev färre, att krigaryrket intelängre var lika attraktivt som karriärväg för adelsmän och att statsmakten utvecklade andra mer civiladelar. Behovet av ett krigsmanshus fanns till sist inte längre och institutionen i Vadstena stängde förboende våren 1784, men kassan fanns kvar in på 1970-talet.
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| 36. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 37. |
- Svedäng, Henrik, et al.
(författare)
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On the decline of eastern Baltic cod : we need to take more holistic views into account. Reply to Brander (2022) comment on Svedäng et al. (2022)
- 2022
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Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 79:7, s. 2157-2158
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Tidskriftsartikel (refereegranskat)abstract
- Explaining the recent decline of eastern Baltic cod (EBC) remains scientifically challenging. Brander proposes in a comment to Svedäng et al.that the observed trend in oxygen in SD 25 supports the idea that juvenile cod are balancing the physiological cost of living under mild hypoxiaby offsetting the risk of being eaten by diving seals and cormorants in shallower water with more oxygen. There are a number of objections tothis conjecture, besides the fact that supporting observations are missing. Hence, it is difficult to reconcile the long-term development of EBCunder varying oxygen conditions with the hypothesis that a small reduction in oxygen content can explain the current strong and uniform declinein growth observed in the entire southern Baltic Sea.
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| 38. |
- Svedäng, Henrik, et al.
(författare)
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Re-thinking the “ecological envelope” of Eastern Baltic cod (Gadus morhua) : conditions for productivity, reproduction, and feeding over time
- 2022
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Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 79:3, s. 689-708
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia is presently seen as the principal driver behind the decline of the former dominating Eastern Baltic cod stock (EBC; Gadus morhua). It has been proposed that both worsening conditions for reproduction and lower individual growth, condition, and survival are linked to hypoxia. Here, we elucidate the ecological envelope of EBC in terms of salinity stratification, oxygen content, and benthic animal biomasses, and how it has affected EBC productivity over time. The spawning conditions started deteriorating in the Gotland Deep in the 1950s due to oxygen depletion. In contrast, in the Bornholm Basin, hydrographic conditions have remained unchanged over the last 60 years. Indeed, the current extent of both well-oxygenated areas and the frequency of hypoxia events do not differ substantially from periods with high EBC productivity in the 1970s–1980s. Furthermore, oxygenated and therefore potentially suitable feeding areas are abundant in all parts of the Baltic Sea, and our novel analysis provides no evidence of a reduction in benthic food sources for EBC over the last 30 years. We find that while reproduction failure is intricately linked to hydrographic dynamics, a relationship between the spread of hypoxia and the decline in EBC productivity during the last decades cannot be substantiated.
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