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Overexpression of H...
Overexpression of Human Estrogen Biosynthetic Enzyme Hydroxysteroid (17beta) Dehydrogenase Type 1 Induces Adenomyosis-like Phenotype in Transgenic Mice
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Heinosalo, T. (författare)
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Rytkonen, K. T. (författare)
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Saarinen, N. (författare)
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Jarvensivu, P. (författare)
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- Damdimopoulou, P. (författare)
- Karolinska Institutet
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Strauss, L. (författare)
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Orasniemi, S. (författare)
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Horshauge, P. (författare)
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Gabriel, M. (författare)
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Koskimies, P. (författare)
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- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Kronqvist, P. (författare)
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- Poutanen, Matti (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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(creator_code:org_t)
- 2022-04-27
- 2022
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:9
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) is an enzyme that converts estrone to estradiol, while adenomyosis is an estrogen-dependent disease with poorly understood pathophysiology. In the present study, we show that mice universally over-expressing human estrogen biosynthetic enzyme HSD17B1 (HSD17B1TG mice) present with adenomyosis phenotype, characterized by histological and molecular evaluation. The first adenomyotic changes with endometrial glands partially or fully infiltrated into the myometrium appeared at the age of 5.5 months in HSD17B1TG females and became more prominent with increasing age. Preceding the phenotype, increased myometrial smooth muscle actin positivity and increased amount of glandular myofibroblast cells were observed in HSD17B1TG uteri. This was accompanied by transcriptomic upregulation of inflammatory and estrogen signaling pathways. Further, the genes upregulated in the HSD17B1TG uterus were enriched with genes previously observed to be induced in the human adenomyotic uterus, including several genes of the NFKB pathway. A 6-week-long HSD17B1 inhibitor treatment reduced the occurrence of the adenomyotic changes by 5-fold, whereas no effect was observed in the vehicle-treated HSD17B1TG mice, suggesting that estrogen is the main upstream regulator of adenomyosis-induced uterine signaling pathways. HSD17B1 is considered as a promising drug target to inhibit estrogen-dependent growth of endometrial disorders. The present data indicate that HSD17B1 over-expression in TG mice results in adenomyotic changes reversed by HSD17B1 inhibitor treatment and HSD17B1 is, thus, a potential novel drug target for adenomyosis.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- adenomyosis
- estrogen
- factor-kappa-b
- 17-beta-hydroxysteroid-dehydrogenase type-1
- in-vivo
- expression
- receptor
- endometriosis
- activation
- cancer
- cells
- gene
- Biochemistry & Molecular Biology
- Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Heinosalo, T.
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Rytkonen, K. T.
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Saarinen, N.
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Jarvensivu, P.
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Damdimopoulou, P ...
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Strauss, L.
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visa fler...
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Orasniemi, S.
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Horshauge, P.
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Gabriel, M.
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Koskimies, P.
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Ohlsson, Claes, ...
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Kronqvist, P.
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Poutanen, Matti
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visa färre...
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- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet