In order to establish the functional role of epigenetic modifications associated with fetal alcohol exposure in repression of D2R expression and prolactinoma development, we tested the effects of epigenetic modulatory drugs such as 5-Aza-dC (a DNA methylation inhibitor), TSA (a HDAC inhibitor) and the two drugs in combination on the estradiol-induced changes in the levels of pituitary D2R mRNA, pituitary weight and plasma PRL. We found that 5-Aza-dC significantly increased D2R expression in AF animals compared to the vehicle control (). TSA treatment moderately increased D2R expression in AF compared to vehicle control, but it did not achieve significance. 5-AZAdC and TSA in combination also significantly increased D2R expression compared to vehicle control. We also found that 5-Aza-dC treatment significantly increased pituitary D2R protein levels compared to vehicle control after 60 days of estrogen treatment. The increase of D2R protein is higher in AF animals compared AD or PF controls (). We found that both 5-Aza-dC and TSA were effective in reducing pituitary weight and plasma PRL levels in AF rats to the extent that these values are not different from AD and PF controls (). These drugs did not change pituitary weight and plasma PRL levels in AD and PF rats, suggesting that the epigenetic modulatory drugs reverse fetal alcohol induced epigenetic modifications thereby increasing D2R expression that results in reduced pituitary weight and plasma PRL levels. Together these data suggest that fetal alcohol exposure epigenetically programs the pituitary to repress D2R gene expression and stimulate pituitary lactotropic cell growth and PRL production.
Oct 31, 2013 - Caterpillar D2 tractor overview
The Caterpillar D2 was manufactured by Caterpillar Inc. in the factory that was located in Peoria, Illinois, USA. It stopped being manufactured in the year of 1957. The base frame of this model of tractor is a crawler. The weight of the Caterpillar D2 ranges from about 7420 to 8536 pounds depending upon the year it was manufactured. There are 5 forward gears and 1 reverse gear. Caterpillar manufactured a total of 26,454 D2 model tractors. Caterpillar began manufacturing new tractors, including the D2 model, in response to the "New Deal" programs that were initiated by President Franklin Roosevelt to stimulate America's economy.
Dimensions & Tires: Weight: 7420 to 8536 pounds
Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells.
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