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| 2. |
- Heinosalo, T., et al.
(författare)
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Overexpression of Human Estrogen Biosynthetic Enzyme Hydroxysteroid (17beta) Dehydrogenase Type 1 Induces Adenomyosis-like Phenotype in Transgenic Mice
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Franke, A., et al.
(författare)
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Status and trends of circumpolar peregrine falcon and gyrfalcon populations
- 2020
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:3, s. 762-783
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Tidskriftsartikel (refereegranskat)abstract
- The peregrine falcon (Falco peregrinus) and the gyrfalcon (Falco rusticolus) are top avian predators of Arctic ecosystems. Although existing monitoring efforts are well established for both species, collaboration of activities among Arctic scientists actively involved in research of large falcons in the Nearctic and Palearctic has been poorly coordinated. Here we provide the first overview of Arctic falcon monitoring sites, present trends for long-term occupancy and productivity, and summarize information describing abundance, distribution, phenology, and health of the two species. We summarize data for 24 falcon monitoring sites across the Arctic, and identify gaps in coverage for eastern Russia, the Arctic Archipelago of Canada, and East Greenland. Our results indicate that peregrine falcon and gyrfalcon populations are generally stable, and assuming that these patterns hold beyond the temporal and spatial extents of the monitoring sites, it is reasonable to suggest that breeding populations at broader scales are similarly stable. We have highlighted several challenges that preclude direct comparisons of Focal Ecosystem Components (FEC) attributes among monitoring sites, and we acknowledge that methodological problems cannot be corrected retrospectively, but could be accounted for in future monitoring. Despite these drawbacks, ample opportunity exists to establish a coordinated monitoring program for Arctic-nesting raptor species that supports CBMP goals.
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- Kaivo-Oja, Noora, et al.
(författare)
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Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 88:2, s. 755-762
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Tidskriftsartikel (refereegranskat)abstract
- The TGF beta family member growth differentiation factor-9 (GDF-9) is an oocyte-derived factor that is essential for mammalian ovarian folliculogenesis. GDF-9 mRNAs have been shown to be expressed in the human ovarian follicle from the primary follicle stage onward, and recombinant GDF-9 has been shown to promote human ovarian follicle growth in vitro. In this study with primary cultures of human granulosa-luteal (hGL) cells, we investigated whether recombinant GDF-9 activates components of the Smad signaling pathways known to be differentially activated by TGF beta and the bone morphogenetic proteins (BMPs). As with TGF beta, GDF-9 treatment caused the phosphorylation of endogenous 53-kDa proteins detected in Western blots with antiphospho-Smad2 antibodies (alpha PS2). However, unlike BMP-2, GDF-9 did not activate the phosphorylation of antiphospho-Smad1 antibody (alphaPS1)-immunoreactive proteins in hGL cells. Infection of hGL cells with an adenovirus expressing Smad2 (Ad-Smad2) confirmed that GDF-9 activates specifically phosphorylation of the Smad2 protein. Infection of hGL cells with Ad-Smad7, which expresses the inhibitory Smad7 protein, suppressed the levels of both GDF-9-induced endogenous and adenoviral alpha PS2-reactive proteins. Furthermore, GDF-9 increased the steady state levels of inhibin beta(B)-subunit mRNAs in hGL cells and strongly stimulated the secretion of dimeric inhibin B. Again, Ad-Smad7 blocked GDF-9-stimulated inhibin B production in a concentration-dependent manner. We identify here for the first time distinct molecular components of the GDF-9 signaling pathway in the human ovary. Our data suggest that GDF-9 mediates its effect through the pathway commonly activated by TGF beta and activin, but not that activated by many BMPs. The results are also consistent with the suggestion that in addition to endocrine control of inhibin production by gonadotropins, a local paracrine control of inhibin production is likely to occur via oocyte-derived factors in the human ovary.
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