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- Yusuf, D, et al.
(författare)
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The transcription factor encyclopedia
- 2012
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Windahl, Sara H, 1971, et al.
(författare)
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Estrogen receptor-alpha in osteocytes is important for trabecular bone formation in male mice
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 110:6, s. 2294-2299
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Tidskriftsartikel (refereegranskat)abstract
- The bone-sparing effect of estrogen in both males and females is primarily mediated via estrogen receptor-alpha (ER alpha), encoded by the Esr1 gene. ER alpha in osteoclasts is crucial for the trabecular bone-sparing effect of estrogen in females, but it is dispensable for trabecular bone in male mice and for cortical bone in both genders. We hypothesized that ER alpha in osteocytes is important for trabecular bone in male mice and for cortical bone in both males and females. Dmp1-Cre mice were crossed with ER alpha(flox/flox) mice to generate mice lacking ER alpha protein expression specifically in osteocytes (Dmp1-ER alpha(-/-)). Male Dmp1-ER alpha(-/-) mice displayed a substantial reduction in trabecular bone volume (-20%, P < 0.01) compared with controls. Dynamic histomorphometry revealed reduced bone formation rate (-45%, P < 0.01) but the number of osteoclasts per bone surface was unaffected in the male Dmp1-ER alpha(-/-) mice. The male Dmp1-ER alpha(-/-) mice had reduced expression of several osteoblast/osteocyte markers in bone, including Runx2, Sp7, and Dmp1 (P < 0.05). Gonadal intact Dmp1-ER alpha(-/-) female mice had no significant reduction in trabecular bone volume but ovariectomized Dmp1-ER alpha(-/-) female mice displayed an attenuated trabecular bone response to supraphysiological E2 treatment. Dmp1-ER alpha(-/-) mice of both genders had unaffected cortical bone. In conclusion, ER alpha in osteocytes regulates trabecular bone formation and thereby trabecular bone volume in male mice but it is dispensable for the trabecular bone in female mice and the cortical bone in both genders. We propose that the physiological trabecular bone-sparing effect of estrogen is mediated via ER alpha in osteocytes in males, but via ER alpha in osteoclasts in females.
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| 6. |
- Lundholm, L, et al.
(författare)
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The estrogen receptor {alpha}-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms
- 2008
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Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 199:2, s. 275-286
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to validate the role of estrogen receptor alpha (ERalpha) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERalpha-selective agonist propyl pyrazole triol (PPT) or 17beta-estradiol (E(2)) in ob/ob mice. Female ob/ob mice were treated with PPT, E(2) or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPT and E(2) treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E(2) treatment. However, PPT and E(2) had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E(2) treatment. In the liver, treatment with E(2) and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPT exerts anti-diabetic effects, and these effects are mediated via ERalpha.
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| 10. |
- Antonson, P., et al.
(författare)
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aP2-Cre-Mediated Inactivation of Estrogen Receptor Alpha Causes Hydrometra
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ER alpha is regulated by the aP2 (fatty acid binding protein 4) promoter. ER alpha-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ER alpha(flox/flox) mice. As expected, ER alpha mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ER alpha levels in the hypothalamus of aP2-Cre/ER alpha(flox/flox) mice. Phenotypic analysis revealed that aP2-Cre/ER alpha(flox/flox) female mice were infertile. In line with this, aP2-Cre/ER alpha(flox/flox) female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ER alpha(flox/flox) female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ER alpha(flox/flox) mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ER alpha(flox/flox) mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction.
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