Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we showed that supplementation with nitric oxide (NO) via donor nitroglycerin (NG) alleviated the ovariectomy and corticosteroid-induced bone loss in rats. In humans, high doses or frequent applications of NG (i.e., for angina) lead to rapid loss of its efficacy in relieving angina. To examine whether there is a similar effect on the loss of efficacy of NG on bone, we examined the frequency-dependent effects of NG on bone mineral density (BMD), bone mass, trabecular bone volumes (BV/TV), and blood pressure in rats. Thirty 7-month-old female Brown Norway rats underwent ovariectomy, and an additional six rats were sham-operated. The ovariectomized rats were treated either with vehicle (ovariectomized control), 17beta-estradiol (E2; positive control), or 0.2 mg NG (via dermal application) once, twice, or three times a day. Before and at the end of the 10-week treatment period, BMD of the lumbar spine was measured by dual-energy X-ray absorptiometric (DXA) scanning and expressed as a percentage change. BMD in ovariectomized rats was significantly lower (-2.5 +/- 2.0%) compared with the sham-operated rats (+6.3 +/- 5.3%; p < 0.01). Estrogen therapy completely abolished the ovariectomy-induced potential bone loss (+5.9 +/- 3.4%). Application of NG once daily also completely prevented (+6.2 +/- 2.8%; p < 0.01) the ovariectomy-induced bone loss (i.e., it was as effective as estrogen). However, the beneficial effects of NG on BMD were significantly reduced with increased frequency of application of NG (+1.9 +/- 2.1%, twice a day and -0.2 +/- 3.3% three times a day). Estrogen or once daily administration of NG preserved femur weights, BV/TV, and decreased urinary deoxypyridinoline levels as expected. However, a higher level of serum osteocalcin and bone-specific alkaline phosphatase levels were maintained only with once daily administration of NG. There were no adverse effects of these doses of NG on blood pressure, but a tendency to lower blood pressure was noticed with increased frequency of NG. These results confirmed our previous findings that NO donors counteract the bone loss associated with estrogen deficiency. However, these beneficial effects of maintaining BMD are lost with increased frequency of NG application.
 ...
PMID:Frequency-dependent effect of nitric oxide donor nitroglycerin on bone. 1084 Nov 80

The article highlighted in this issue is "Bisphenol A-Induced Increase in Uterine Weight and Alterations in Uterine Morphology in Ovariectomized B6C3F1 Mice: Role of the Estrogen Receptor" by Andriana D. Papaconstantinou, Thomas H. Umbreit, Benjamin R. Fisher, Peter L. Goering, Nicholas T. Lappas, and Ken M. Brown (pp. 332-339).
 ...
PMID:Bisphenol A and related endocrine disruptors. 1091 Sep 79

Estrogen treatment to rats of the Fischer 344 (F344) strain induces growth of pituitary tumors that exhibit accelerated cell proliferation, breakdown of basement membrane, and formation of hemorrhagic lakes. Estrogen-dependent pituitary growth is due to variation in a group of quantitative trait loci (QTL), called Edpm for estrogen-dependent pituitary mass, that we previously identified in an F(2) intercross of F344 and the tumor-resistant Brown Norway strain. We previously identified 5 QTL, and microsatellite markers developed since our earlier work have allowed us to scan new chromosomal regions, resulting in two new QTL for estrogen-dependent pituitary mass: Edpm9-2 and a possible QTL on the X Chromosome (Chr). Here we report evidence that these QTL differ from each other in how they affect growth. To examine the effect of the Edpm QTL on biochemical components of tumor growth, we tested their effects in 138 progeny of a backcross to the F344 strain which were given a 10-week chronic estrogen treatment. Hemoglobin/DNA ratio (a measure of blood volume relative to cell number) and total pituitary DNA (a measure of cell number) correlated only weakly, and very large pituitaries were observed which had a low hemoglobin/DNA ratio resembling a normal gland. Through QTL mapping, we found that Edpm2-1, Edpm3, Edpm5, and Edpm9-2 all had significant effects on pituitary mass, but Edpm2-1 and Edpm9-2 primarily affected DNA content, Edpm5 primarily affected hemoglobin/DNA ratio, and Edpm3 affected all traits equally.
 ...
PMID:Different functions of QTL for estrogen-dependent tumor growth of the rat pituitary. 1100 99

Estrogen regulates the amount of white adipose tissue (WAT) in females, but its role in males and whether WAT effects involve estrogen receptor-alpha (ERalpha) or ERbeta were unclear. We analyzed the role of ERalpha in WAT and brown adipose tissue by comparing these tissues in wild-type (WT) and ERalpha-knockout (alphaERKO) male and female mice. Brown adipose tissue weight was similar in alphaERKO and WT males at all ages. Progressive increases in WAT were seen in alphaERKO males with advancing age. Epididymal, perirenal, and inguinal WAT weighed 139-185% more in alphaERKO than in WT males by 270-360 days of age. Epididymal and perirenal adipocyte size was increased 20% in alphaERKO males. Adipocyte number was 82-168% greater in fat pads of alphaERKO vs. WT males. Compared with WT, 90-day-old alphaERKO females had increases in fat pad weights (54-103%), adipocyte size, and number. Both alphaERKO males and females had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase. Energy intake was equal in WT and alphaERKO males, indicating that obesity was not induced by hyperphagia. In contrast, energy expenditure was reduced by 11% in alphaERKO compared with WT males, indicating that altered energy expenditure may be important for the observed obesity. In summary, ERalpha absence causes adipocyte hyperplasia and hypertrophy, insulin resistance, and glucose intolerance in both sexes. These results are evidence that estrogen/ERalpha signaling is critical in female and male WAT; obesity in alphaERKO males involves a mechanism of reduced energy expenditure rather than increased energy intake.
 ...
PMID:Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. 1107 86

In certain rat strains, chronic estrogen administration can lead to pyometritis, an inflammation of the uterus accompanied by infection and the accumulation of intraluminal pus. In this article, we report that the Brown Norway (BN) rat is highly susceptible to pyometritis induced by 17beta-estradiol (E2). The susceptibility of the BN rat to E2-induced pyometritis appears to segregate as a recessive trait in crosses to the resistant August x Copenhagen Irish (ACI) strain. In a (BN x ACI)F(2) population, we find strong evidence for a major genetic determinant of susceptibility to E2-induced pyometritis on rat chromosome 5 (RNO5). Our data are most consistent with a model in which the BN allele of this locus, designated Eutr1 (Estrogen-induced uterine response 1), acts in an incompletely dominant manner to control E2-induced pyometritis. Furthermore, we have confirmed the contribution of Eutr1 to E2-induced uterine pyometritis using an RNO5 congenic rat strain. In addition to Eutr1, we obtained evidence suggestive of linkage for five additional loci on RNO2, 4, 11, 17, and X that control susceptibility to E2-induced pyometritis in the (BN x ACI)F(2) population.
 ...
PMID:Genetic mapping of Eutr1, a locus controlling E2-induced pyometritis in the Brown Norway rat, to RNO5. 1628 1

Hy-Line W-36, W-98, and Brown hens lay approximately the same number of eggs/hen housed to 80 wk; however, little is known about differences in performance during heat stress (HS). Two experiments were performed. The first experiment evaluated intestinal calcium uptake (CaT), heat shock protein-70 (HSP70) liver expression, and endocrine status in the 3 strains under heat stress in response to 1 h of transient exposure to high temperature before onset of 18 h of HS. The second experiment evaluated the differences between W-36 and W-98 in acid-base status observed at 2 different ambient temperatures. The HSP70 and CaT data were analyzed as a completely randomized design (CRD) using a 3 x 2 factorial with strain as a 1 factor and preexposed and control treatments as the other. Estrogen and progesterone data were analyzed as a CRD using repeated measures in a 3 x 2 x 2 factorial with strain as a the first factor, preexposure and control treatments as the second factor, and phase of blood collection as the third factor. The data of the second experiment were analyzed as a CRD using repeated measures in a 2 x 2 x 2 factorial with strain, temperature, and phase of blood collection as the factors. The method applied in both experiments was based on the mixed model (SAS). The results show a strain effect, with the higher CaT in the W-36. The results indicated that transient exposure to HS did not induce changes in HSP70 liver expression. In the second experiment, the blood gas values did not differ between strains, except for the partial pressure of CO(2), in which the values at 22 degrees C are higher for the W-36. At 38 degrees C, there was an increase in blood pH and a reduction in HCO(3)(-) in both strains. The results indicate that endocrine, acid-base status, and Ca homeostasis represent important factors to be considered in assessing genetic differences for thermotolerance.
 ...
PMID:Physiological changes to transient exposure to heat stress observed in laying hens. 1729 67