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National Institute of Environmental Health Sciences

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Publication Detail

Title: The effect of progesterone dose on gene expression after traumatic brain injury.

Authors: Anderson, Gail D; Farin, Federico M; Bammler, Theo K; Beyer, Richard P; Swan, Alicia A; Wilkerson, Hui-Wen; Kantor, Eric D; Hoane, Michael R

Published In J Neurotrauma, (2011 Sep)

Abstract: Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10ýýýmg/kg or 20ýýýmg/kg given i.p.) was started 4ýýýh post-injury and administered every 12ýýýh post-injury for up to 72ýýýh, with the last injection 12ýýýhr prior to death for the 24ýýýh and 72ýýýh groups. In the CCI-injured vehicle group compared to non-injured animals, expression of 1,114, 4,229, and 291 distinct genes changed >1.5-fold (p<0.05) at 24ýýýh, 72ýýýh, and 7 days, respectively. At 24ýýýh, the effect of low-dose progesterone on differentially expressed genes was <20% the effect of higher dose compared to vehicle. GO analysis identified a significant effect of low- and high-dose progesterone treatment compared to vehicle on DNA damage response. At 72ýýýh, high-dose progesterone treatment compared to vehicle affected expression of almost twice as many genes as did low-dose progesterone. Both low- and high-dose progesterone resulted in expression of genes regulating inflammatory response and apoptosis. At 7 days, there was only a modest difference in high-dose progesterone compared to vehicle, with only 14 differentially expressed genes. In contrast, low-dose progesterone resulted in 551 differentially expressed genes compared to vehicle. GO analysis identified genes for the low-dose treatment involved in positive regulation of cell proliferation, innate immune response, positive regulation of anti-apoptosis, and blood vessel remodeling.

PubMed ID: 21770760 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis/drug effects; Apoptosis/genetics; Brain Injuries/genetics; Brain Injuries/metabolism*; Cerebral Cortex/drug effects*; Cerebral Cortex/metabolism; Dose-Response Relationship, Drug; Gene Expression/drug effects*; Male; Progesterone/administration & dosage*; Progestins/administration & dosage*; Rats; Rats, Sprague-Dawley

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