PMID- 29721586
OWN - NLM
STAT- MEDLINE
DCOM- 20190903
LR  - 20190903
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 92
IP  - 6
DP  - 2018 Jun
TI  - Corticosteroid-binding globulin, induced in testicular Leydig cells by 
      perfluorooctanoic acid, promotes steroid hormone synthesis.
PG  - 2013-2025
LID - 10.1007/s00204-018-2207-y [doi]
AB  - Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely 
      applied in industrial and consumer products. It is a ubiquitous environmental 
      pollutant and suspected endocrine disruptor. Corticosteroid-binding globulin 
      (CBG) is a monomeric glycoprotein that can bind specifically to anti-inflammatory 
      steroids, such as glucocorticoids and progesterone, in circulation. Our previous 
      proteomic profile analysis revealed that CBG levels increased in testes after 
      PFOA treatment. In the present study, we verified its increase in mouse testes 
      following oral exposure to PFOA (0, 1.25 and 5 mg/kg/day for 28 days) by 
      immunohistochemical analysis and Western blotting. In addition, RNA fluorescence 
      in situ hybridization (FISH) confirmed that testicular CBG was specifically 
      expressed in Leydig cells. Serum CBG levels in all three PFOA groups also 
      increased, accompanied by increased corticosterone in the 5 and 20 mg/kg/day 
      groups and decreased adrenocorticotropic hormone in the 20 mg/kg/day group. Thus, 
      the influence of PFOA on blood CBG may change free steroid hormone 
      concentrations, thereby serving as an endocrine disruptor. A stimulation effect 
      of PFOA on CBG was also observed in vitro using the Leydig tumor mLTC-1 cell 
      line. Overexpression of CBG in mLTC-1 cells increased progesterone release in 
      culture media. In addition, CBG-induced proteins involved in steroidogenesis in 
      mLTC-1 cells, including steroidogenic acute regulatory protein (StAR), cytochrome 
      P450 cholesterol side-chain cleavage enzyme (CYP11A1), 17alpha-hydroxylase/17,20 
      lyase (CYP17A1), and 3beta-hydroxysteroid dehydrogenase (3beta-HSD), which may be the 
      mechanism behind increased progesterone. Furthermore, the production and release 
      of CBG in mLTC-1 cells were also induced by luteinizing hormone, though this 
      mechanism requires further exploration.
FAU - Sun, Sujie
AU  - Sun S
AD  - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of 
      China.
FAU - Wang, Jianshe
AU  - Wang J
AD  - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing, 100101, People's Republic of China. 
      jianshewang@ioz.ac.cn.
FAU - Lu, Yin
AU  - Lu Y
AD  - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
FAU - Dai, Jiayin
AU  - Dai J
AD  - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20180502
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Caprylates)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Fluorocarbons)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 9010-38-2 (Transcortin)
RN  - 947VD76D3L (perfluorooctanoic acid)
SB  - IM
MH  - Animals
MH  - Caprylates/*toxicity
MH  - Cell Culture Techniques
MH  - Cell Line, Tumor
MH  - Endocrine Disruptors/*toxicity
MH  - Fluorocarbons/*toxicity
MH  - Leydig Cells/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Progesterone/*biosynthesis
MH  - Testis/drug effects/metabolism
MH  - Transcortin/genetics/*metabolism
OTO - NOTNLM
OT  - Corticosteroid-binding globulin
OT  - Leydig cell
OT  - Perfluorooctanoic acid
OT  - Progesterone
EDAT- 2018/05/04 06:00
MHDA- 2019/09/04 06:00
CRDT- 2018/05/04 06:00
PHST- 2018/01/11 00:00 [received]
PHST- 2018/04/25 00:00 [accepted]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2019/09/04 06:00 [medline]
PHST- 2018/05/04 06:00 [entrez]
AID - 10.1007/s00204-018-2207-y [pii]
AID - 10.1007/s00204-018-2207-y [doi]
PST - ppublish
SO  - Arch Toxicol. 2018 Jun;92(6):2013-2025. doi: 10.1007/s00204-018-2207-y. Epub 2018 
      May 2.