PMID- 31397875
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230413
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 172
IP  - 1
DP  - 2019 Nov 1
TI  - Ozone-Induced Dysregulation of Neuroendocrine Axes Requires Adrenal-Derived 
      Stress Hormones.
PG  - 38-50
LID - 10.1093/toxsci/kfz182 [doi]
AB  - Acute ozone inhalation increases circulating stress hormones through activation 
      of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes. 
      Rats with adrenalectomy (AD) have attenuated ozone-induced lung responses. We 
      hypothesized that ozone exposure will induce changes in circulating 
      pituitary-derived hormones and global gene expression in the brainstem and 
      hypothalamus, and that AD will ameliorate these effects. Male Wistar-Kyoto rats 
      (13 weeks) that underwent sham surgery (SHAM) or AD were exposed to ozone (0.8 
      ppm) or filtered-air for 4 h. In SHAM rats, ozone exposure decreased circulating 
      thyroid-stimulating hormone (TSH), prolactin (PRL), and luteinizing hormone (LH). 
      AD prevented reductions in TSH and PRL, but not LH. AD increased 
      adrenocorticotropic hormone approximately 5-fold in both air- and ozone-exposed 
      rats. AD in air-exposed rats resulted in few significant transcriptional 
      differences in the brainstem and hypothalamus (approximately 20 genes per 
      tissue). In contrast, ozone-exposure in SHAM rats resulted in either increases or 
      decreases in expression of hundreds of genes in the brainstem and hypothalamus 
      relative to air-exposed SHAM rats (303 and 568 genes, respectively). 
      Differentially expressed genes from ozone exposure were enriched for pathways 
      involving hedgehog signaling, responses to alpha-interferon, hypoxia, and mTORC1, 
      among others. Gene changes in both brain areas were analogous to those altered by 
      corticosteroids and L-3,4-dihydroxyphenylalanine, suggesting a role for 
      endogenous glucocorticoids and catecholamines. AD completely prevented this 
      ozone-induced transcriptional response. These findings show that short-term ozone 
      inhalation promotes a shift in brainstem and hypothalamic gene expression that is 
      dependent upon the presence of circulating adrenal-derived stress hormones. This 
      is likely to have profound downstream influence on systemic effects of ozone.
CI  - Published by Oxford University Press on behalf of the Society of Toxicology 2019. 
      This work is written by US Government employees and is in the public domain in 
      the US.
FAU - Henriquez, Andres R
AU  - Henriquez AR
AD  - Oak Ridge Institute for Science and Education, Research Triangle Park, North 
      Carolina.
FAU - House, John S
AU  - House JS
AD  - Bioinformatics Research Center.
AD  - Center for Human Health and the Environment, North Carolina State University, 
      Raleigh, North Carolina.
FAU - Snow, Samantha J
AU  - Snow SJ
AUID- ORCID: 0000-0003-1812-8582
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina.
AD  - ICF, Durham, North Carolina.
FAU - Miller, Colette N
AU  - Miller CN
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina.
FAU - Schladweiler, Mette C
AU  - Schladweiler MC
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina.
FAU - Fisher, Anna
AU  - Fisher A
AD  - Research Cores Unit.
FAU - Ren, Hongzu
AU  - Ren H
AD  - Research Cores Unit.
FAU - Valdez, Matthew
AU  - Valdez M
AD  - Oak Ridge Institute for Science and Education, Research Triangle Park, North 
      Carolina.
FAU - Kodavanti, Prasada R
AU  - Kodavanti PR
AD  - Toxicity Assessment Division, National Health and Environmental Effects Research 
      Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North 
      Carolina.
FAU - Kodavanti, Urmila P
AU  - Kodavanti UP
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina.
LA  - eng
GR  - EPA999999/ImEPA/Intramural EPA/United States
GR  - T32 ES007126/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
SB  - IM
PMC - PMC9344225
MID - NIHMS1824595
OTO - NOTNLM
OT  - adrenalectomy
OT  - brainstem
OT  - hypothalamus
OT  - neuroendocrine hormones
OT  - ozone
OT  - pituitary
EDAT- 2019/08/10 06:00
MHDA- 2019/08/10 06:01
PMCR- 2022/08/02
CRDT- 2019/08/10 06:00
PHST- 2019/08/10 06:01 [medline]
PHST- 2019/08/10 06:00 [pubmed]
PHST- 2019/08/10 06:00 [entrez]
PHST- 2022/08/02 00:00 [pmc-release]
AID - 5545529 [pii]
AID - 10.1093/toxsci/kfz182 [doi]
PST - ppublish
SO  - Toxicol Sci. 2019 Nov 1;172(1):38-50. doi: 10.1093/toxsci/kfz182.