Persistent Suppression of Hepatic CYP2A1 Expression and Serum Triiodothyronine Levels by Tamoxifen in Intact Female Rats: Dose-Response Analysis and Comparison with 4-Hydroxytamoxifen, Fulvestrant (ICI 182,780), and 17β-Estradiol-3-benzoate

2002 ◽  
Vol 302 (2) ◽  
pp. 584-593 ◽  
Author(s):  
Ludger M. Ickenstein ◽  
Stelvio M. Bandiera
Keyword(s):  
Dose Response ◽  
Female Rats ◽  
Response Analysis ◽  
Intact Female ◽  
Ici 182,780 ◽  
17Β Estradiol

Gender-specific reduction in contractility and [Ca2+]iin vascular smooth muscle cells of female rat

2000 ◽  
Vol 278 (4) ◽  
pp. C834-C844 ◽  
Author(s):  
Jason G. Murphy ◽  
Raouf A. Khalil
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Female Rats ◽  
Cell Contraction ◽  
Intact Female ◽  
Intact Male ◽  
17Β Estradiol ◽  
Gender Specific

The hypothesis that vascular protection in females and its absence in males reflects gender differences in [Ca2+]iand Ca2+mobilization mechanisms of vascular smooth muscle contraction was tested in fura 2-loaded aortic smooth muscle cells isolated from intact and gonadectomized male and female Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In WKY cells incubated in Hanks' solution (1 mM Ca2+), the resting length and [Ca2+]iwere significantly different in intact males (64.5 ± 1.2 μm and 83 ± 3 nM) than in intact females (76.5 ± 1.5 μm and 64 ± 7 nM). In intact male WKY, phenylephrine (Phe, 10−5M) caused transient increase in [Ca2+]ito 428 ± 13 nM followed by maintained increase to 201 ± 8 nM and 32% cell contraction. In intact female WKY, the Phe-induced [Ca2+]itransient was not significantly different, but the maintained [Ca2+]i(159 ± 7 nM) and cell contraction (26%) were significantly less than in intact male WKY. In Ca2+-free (2 mM EGTA) Hanks', Phe and caffeine (10 mM) caused transient increases in [Ca2+]iand contraction that were not significantly different between males and females. Membrane depolarization by 51 mM KCl caused 31% cell contraction and increased [Ca2+]ito 259 ± 9 nM in intact male WKY, which were significantly greater than a 24% contraction and 214 ± 8 nM [Ca2+]iin intact female WKY. Maintained Phe- and KCl-stimulated cell contraction and [Ca2+]iwere significantly greater in SHR than WKY in all groups of rats. Reduction in cell contraction and [Ca2+]iin intact females compared with intact males was significantly greater in SHR (∼30%) than WKY (∼20%). No significant differences in cell contraction or [Ca2+]iwere observed between castrated males, ovariectomized (OVX) females, and intact males, or between OVX females with 17β-estradiol implants and intact females. Exogenous application of 17β-estradiol (10−8M) to cells from OVX females caused greater reduction in Phe- and KCl-induced contraction and [Ca2+]iin SHR than WKY. Thus the basal, maintained Phe- and depolarization-induced [Ca2+]iand contraction of vascular smooth muscle triggered by Ca2+entry from the extracellular space exhibit differences depending on gender and the presence or absence of female gonads. Cell contraction and [Ca2+]idue to Ca2+release from the intracellular stores are not affected by gender or gonadectomy. Gender-specific reduction in contractility and [Ca2+]iin vascular smooth muscle of female rats is greater in SHR than WKY rats.

scholarly journals Investigation of central versus peripheral effects of estradiol in ovariectomized mice

2005 ◽  
Vol 187 (2) ◽  
pp. 303-309 ◽  
Author(s):  
Niklas Andersson ◽  
Ulrika Islander ◽  
Emil Egecioglu ◽  
Elin Löf ◽  
Charlotte Swanson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Dose Response ◽  
Mineral Content ◽  
Target Tissue ◽  
Primary Target ◽  
Response Curves ◽  
Ici 182,780 ◽  
Ovariectomized Mice ◽  
17Β Estradiol ◽  
Sparing Effect

It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose–response of central (i.c.v) 17β-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose–response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.

scholarly journals Biphasic Effects of the Natural Estrogen 17β-Estradiol on Hepatic Cholesterol Metabolism in Intact Female Rats

2000 ◽  
Vol 20 (7) ◽  
pp. 1817-1823 ◽  
Author(s):  
Paolo Parini ◽  
Bo Angelin ◽  
Anneli Stavréus-Evers ◽  
Bo Freyschuss ◽  
Håkan Eriksson ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Female Rats ◽  
Hepatic Cholesterol ◽  
Intact Female ◽  
17Β Estradiol

A Dose-Response Analysis of Nicotine Sensitization in Adolescent Rats D2-Primed as Neonates

2010 ◽  
Author(s):  
Elizabeth A. Hanchak ◽  
Meredith L. Smith ◽  
Jessie J. Smith ◽  
Marla K. Perna ◽  
Russell W. Brown
Keyword(s):  
Dose Response ◽  
Response Analysis ◽  
Adolescent Rats

ENCORE: A weight-based exacerbation dose response analysis of mepolizumab in severe asthma with eosinophilic phenotype

Pneumologie ◽  
2017 ◽  
Vol 71 (S 01) ◽  
pp. S1-S125
Author(s):  
I Pouliquen ◽  
D Austin ◽  
N Gunsoy ◽  
SW Yancey
Keyword(s):  
Severe Asthma ◽  
Dose Response ◽  
Response Analysis

scholarly journals Sleep duration and all-cause mortality in the elderly in China: a population-based cohort study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yanfeng Ren ◽  
Maohua Miao ◽  
Wei Yuan ◽  
Jiangwei Sun
Keyword(s):  
Cohort Study ◽  
Sleep Duration ◽  
Dose Response ◽  
Cox Regression ◽  
Oldest Old ◽  
The Elderly ◽  
Response Analysis ◽  
Short Sleep Duration ◽  
All Cause Mortality

Abstract Background Although a U-shaped association between sleep duration and all-cause mortality has been found in general population, its association in the elderly adults, especially in the oldest-old, is rarely explored. Methods In present cohort study, we prospectively explore the association between sleep duration and all-cause mortality among 15,092 participants enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2019. Sleep duration and death information was collected by using structured questionnaires. Cox regression model with sleep duration as a time-varying exposure was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). The dose-response association between them was explored via a restricted cubic spline function. Results During an average follow-up of 4.51 (standard deviation, SD: 3.62) years, 10,768 participants died during the follow-up period. The mean (SD) age of the participants was 89.26 (11.56) years old. Compared to individuals with moderate sleep duration (7–8 hours), individuals with long sleep duration (> 8 hours) had a significantly higher risk of all-cause mortality (HR: 1.13, 95%CI: 1.09–1.18), but not among individuals with short sleep duration (≤ 6 hours) (HR: 1.02, 95%CI: 0.96–1.09). Similar results were observed in subgroup analyses based on age and gender. In the dose-response analysis, a J-shaped association was observed. Conclusions Sleep duration was associated with all-cause mortality in a J-shaped pattern in the elderly population in China.

129 Single-fraction stereotactic radiotherapy: A dose-response analysis of arteriovenous malformation obliteration

1997 ◽  
Vol 39 (2) ◽  
pp. 199
Author(s):  
Assem Al Halabi ◽  
Emmanuel Touboul ◽  
Laurent Buffat ◽  
Louis Merienne ◽  
Michel Schlienger ◽  
...  
Keyword(s):  
Arteriovenous Malformation ◽  
Dose Response ◽  
Stereotactic Radiotherapy ◽  
Response Analysis ◽  
Single Fraction

scholarly journals Nonmonotonic Pathway Gene Expression Analysis Reveals Oncogenic Role of p27/Kip1 at Intermediate Dose

2017 ◽  
Vol 16 ◽  
pp. 117693511774013 ◽  
Author(s):  
Hien H Nguyen ◽  
Susan C Tilton ◽  
Christopher J Kemp ◽  
Mingzhou Song
Keyword(s):  
Gene Expression ◽  
Pathway Analysis ◽  
Dose Response ◽  
Response Analysis ◽  
Response Curves ◽  
Cancer Pathways ◽  
Pathway Gene ◽  
Mechanistic Basis ◽  
Functional Pathway ◽  
Squamous Cell Papilloma

The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis—strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems.

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