| 1. |
- Leung, K C, et al.
(författare)
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Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
- 2003
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 100:3, s. 1016-21
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Tidskriftsartikel (refereegranskat)abstract
- Oral estrogen administration attenuates the metabolic action of growth hormone (GH) in humans. To investigate the mechanism involved, we studied the effects of estrogen on GH signaling through Janus kinase (JAK)2 and the signal transducers and activators of transcription (STATs) in HEK293 cells stably expressing the GH receptor (293GHR), HuH7 (hepatoma) and T-47D (breast cancer) cells. 293GHR cells were transiently transfected with an estrogen receptor-alpha expression plasmid and luciferase reporters with binding elements for STAT3 and STAT5 or the beta-casein promoter. GH stimulated the reporter activities by four- to sixfold. Cotreatment with 17beta-estradiol (E(2)) resulted in a dose-dependent reduction in the response of all three reporters to GH to a maximum of 49-66% of control at 100 nM (P < 0.05). No reduction was seen when E(2) was added 1-2 h after GH treatment. Similar inhibitory effects were observed in HuH7 and T-47D cells. E(2) suppressed GH-induced JAK2 phosphorylation, an effect attenuated by actinomycin D, suggesting a requirement for gene expression. Next, we investigated the role of the suppressors of cytokine signaling (SOCS) in E(2) inhibition. E(2) increased the mRNA abundance of SOCS-2 but not SOCS-1 and SOCS-3 in HEK293 cells. The inhibitory effect of E(2) was absent in cells lacking SOCS-2 but not in those lacking SOCS-1 and SOCS-3. In conclusion, estrogen inhibits GH signaling, an action mediated by SOCS-2. This paper provides evidence for regulatory interaction between a sex steroid and the GHJAKSTAT pathway, in which SOCS-2 plays a central mechanistic role.
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| 4. |
- Smith, P B, et al.
(författare)
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Cultural values, sources of guidance, and their relevance to managerial behavior - A 47-nation study
- 2002
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Ingår i: Journal of Cross-Cultural Psychology. - : Sage Publications. - 0022-0221 .- 1552-5422. ; 33:2, s. 188-208
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Tidskriftsartikel (refereegranskat)abstract
- Data are presented showing how middle managers in 47 countries report handling eight specific work events. The data are used to test the ability of cultural value dimensions derived from the work of Hofstede. Trompenaars, and Schwartz to predict the specific sources of guidance on which managers rely. Focusing on sources of guidance is expected to provide a more precise basis than do generalized measures of values for understanding the behaviors that prevail within different cultures. Values are strongly predictive of reliance on those sources of guidance that are relevant to vertical relationships within organizations. Hock ever, values are less successful in predicting reliance on peers and on more tacit sources of guidance. Explaining national differences in these neglected aspects of organizational processes will require greater sensitivity to the culture-specific contexts within which they occur.
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| 5. |
- Leong, Gary M, et al.
(författare)
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Estrogen up-regulates hepatic expression of suppressors of cytokine signaling-2 and -3 in vivo and in vitro.
- 2004
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 145:12, s. 5525-31
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Tidskriftsartikel (refereegranskat)abstract
- Suppressors of cytokine signaling (SOCS) are important negative regulators of cytokine action. We recently reported that estrogen stimulates SOCS-2 expression and inhibits GH signaling in kidney cells. The effects of estrogen on SOCS expression in other tissues are unclear. The aim of this study was to investigate in vivo and in vitro whether estrogen affected SOCS expression in the liver, a major target organ of GH. The in vivo hepatic effects of estrogen on ovariectomized mice lacking estrogen receptor (ER)-alpha, ERbeta, or both and their wild-type littermates were examined by DNA microarray analysis. In vitro, the effects of estrogen on SOCS expression in human hepatoma cells were examined by reverse transcription quantitative PCR. Long-term (3 wk) estrogen treatment induced a 2- to 3-fold increase in hepatic expression of SOCS-2 and -3 in wild-type and ERbeta knockout mice but not in those lacking ERalpha or both ER subtypes. Short-term treatment (at 24 h) increased the mRNA level of SOCS-3 but not SOCS-2. In cultured hepatoma cells, estrogen increased SOCS-2 and -3 mRNA levels by 2-fold in a time- and dose-dependent manner (P < 0.05). Estrogen induced murine SOCS-3 promoter activity by 2-fold (P < 0.05) in constructs containing a region between nucleotides -1862 and -855. Moreover, estrogen and GH had additive effects on the SOCS-3 promoter activity. In summary, estrogen, via ERalpha, up-regulated hepatic expression of SOCS-2 and -3, probably through transcriptional activation. This indicates a novel mechanism of estrogen regulation of cytokine action.
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| 6. |
- Leung, Kin-Chuen, et al.
(författare)
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Estrogen regulation of growth hormone action.
- 2004
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Ingår i: Endocrine reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 25:5, s. 693-721
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Tidskriftsartikel (refereegranskat)abstract
- GH plays a pivotal role in regulating body growth and development, which is modulated by sex steroids. A close interplay between estrogen and GH leads to attainment of gender-specific body composition during puberty. The physiological basis of the interaction is not well understood. Most previous studies have focused on the effects of estrogen on GH secretion. There is also strong evidence that estrogen modulates GH action independent of secretion. Oral but not transdermal administration of estrogen impairs the metabolic action of GH in the liver, causing a fall in IGF-I production and fat oxidation. This results in a loss of lean tissue and a gain of body fat in postmenopausal women and an impairment of GH effect in hypopituitary women on GH replacement. The negative metabolic sequelae are potentially important because of the widespread use of oral estrogen and estrogen-related compounds. Estrogen affects GH action at the level of receptor expression and signaling. More recently, estrogen has been shown to inhibit Janus kinase/signal transducer and activator of transcription signaling by GH via the induction of suppressor of cytokine signaling-2, a protein inhibitor for cytokine signaling. This represents a novel paradigm of steroid regulation of cytokine receptors and is likely to have significance for a diverse range of cytokine function.
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| 10. |
- Linnarsson, Margareta K., et al.
(författare)
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Solubility limit and precipitate formation in Al-doped 4H-SiC epitaxial material
- 2001
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 79:13, s. 2016-2018
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Tidskriftsartikel (refereegranskat)abstract
- Heavily Al-doped 4H-SiC structures have been prepared by vapor phase epitaxy. Subsequent anneals have been carried out in an Ar atmosphere in a rf-heated furnace between 1500 degreesC and 2000 degreesC for 0.5 to 3 h. Secondary ion mass spectrometry has been utilized to obtain Al concentration versus depth as well as lateral distributions (ion images). Transmission electron microscopy (TEM) has been employed to study the crystallinity and determine phase composition after heat treatment. A solubility limit of similar to 2x10(20) Al/cm(3) (1900 degreesC) is extracted. Three-dimensional ion images show that the Al distribution does not remain homogeneous in layers heat treated at 1700 degreesC or above when the Al concentration exceeds 2x10(20) cm(-3). Al-containing precipitates are identified by energy-filtered TEM.
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| 11. |
- Linnarsson, Margareta K., et al.
(författare)
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Solubility limits of dopants in 4H-SiC
- 2003
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Ingår i: Applied Surface Science. - 0169-4332 .- 1873-5584. ; 203, s. 427-432
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Tidskriftsartikel (refereegranskat)abstract
- Epitaxial 4H-SiC structures with heavily boron or aluminium doped layers have been prepared by vapour phase epitaxy. The samples have been annealed in Ar atmosphere in an RF-heated furnace between 1700 and 2000 degreesC for 45 min to 64 h. Secondary ion mass spectrometry has been employed to obtain depth distributions as well as lateral distributions (ion imaging) for boron and aluminium. Transmission electron microscopy has been used to study the crystallinity and determine phase composition. Solubility limits of similar to 1 x 10(20) Al/cm(3) (1700 degreesC) and < 1 x 10(20) B/cm(3) (1900 degreesC) have been deduced.
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| 13. |
- Wong-Leung, J., et al.
(författare)
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A comparison of extended defect formation induced by ion implantation in (0001) and (11(2)over-bar-0) 4H-SiC
- 2003
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Ingår i: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 340, s. 132-136
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Tidskriftsartikel (refereegranskat)abstract
- We study the effect of substrate orientation on defect formation in 4H-SiC. Both (1 1 (2) over bar 0) and (0 0 0 1) n-type 4H-SiC substrates were implanted with 400 keV P. The various samples, both as-implanted samples and annealed, were studied by Rutherford backscattering and channeling and transmission electron microscopy in an attempt to understand the damage evolution and defect structures resulting from different crystal orientations. Secondary ion mass spectrometry (SIMS) was performed for P elemental profiling before and after annealing. We observe a significantly different damage accumulation in the two directions with a broader amorphous layer formed in the c-cut crystal compared to the a-cut crystal. The annealing of the damage results in a range of different defects including dislocation loops and voids in both a-cut and c-cut crystals. The SIMS profiles show in some cases distinct differences between the two crystal directions.
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