PMID- 30414542
OWN - NLM
STAT- MEDLINE
DCOM- 20190204
LR  - 20210816
IS  - 1879-1298 (Electronic)
IS  - 0045-6535 (Linking)
VI  - 217
DP  - 2019 Feb
TI  - Persistent endocrine-disrupting chemicals found in human follicular fluid 
      stimulate the proliferation of granulosa tumor spheroids via GPR30 and IGF1R but 
      not via the classic estrogen receptors.
PG  - 100-110
LID - S0045-6535(18)32115-5 [pii]
LID - 10.1016/j.chemosphere.2018.11.018 [doi]
AB  - Epidemiological studies have found that women have detectable levels of organic 
      pollutants such as hexachlorobenzene (HCB), 2,2-dichlorodiphenyldichloroethylene 
      (p,p'-DDE), polychlorinated biphenyl 153 (PCB153), perfluorooctanoate (PFOA), and 
      perfluorooctane sulfonate (PFOS) in their follicular fluid. Thus, these compounds 
      may directly affect the function of granulosa cells within the ovary and may 
      promote granulosa cell tumor (GCT) progression. Two human GCT cell lines, COV434 
      and KGN, have been used as in vitro model systems to represent juvenile (JGCT) 
      and adult (AGCT) GCT subtypes, respectively. In this study, we found that basal 
      expression of estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and 
      insulin-like growth factor 1 receptor (IGF1R) was higher in the AGCT subtype than 
      in the JGCT subtype. All of the compounds acted as mitogenic factors at low 
      nanomolar concentrations in the JGCT and AGCT forms of GCT. Interestingly, PFOA, 
      PFOS, and HCB stimulated cell proliferation through IGF1R, whereas p,p'-DDE acted 
      through GPR30. Moreover, a mixture of the five compounds also significantly 
      stimulated granulosa cell proliferation; however, the observed effect was lower 
      than predicted. Interestingly, the proliferative effect of a mixture of these 
      compounds was dependent on IGF1R and GPR30 but independent of the classic 
      estrogen receptors. Taken together, our results demonstrate for the first time 
      that mixtures of persistent organic pollutants present in follicular fluids may 
      induce granulosa tumor progression through IGF1R and GPR30 by acting as mitogenic 
      factors in granulosa cells.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Gogola, Justyna
AU  - Gogola J
AD  - Department of Physiology and Toxicology of Reproduction, Institute of Zoology and 
      Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, 
      Poland.
FAU - Hoffmann, Marta
AU  - Hoffmann M
AD  - Department of Physiology and Toxicology of Reproduction, Institute of Zoology and 
      Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, 
      Poland.
FAU - Ptak, Anna
AU  - Ptak A
AD  - Department of Physiology and Toxicology of Reproduction, Institute of Zoology and 
      Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, 
      Poland. Electronic address: anna.ptak@uj.edu.pl.
LA  - eng
PT  - Journal Article
DEP - 20181104
PL  - England
TA  - Chemosphere
JT  - Chemosphere
JID - 0320657
RN  - 0 (ESR1 protein, human)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (GPER1 protein, human)
RN  - 0 (IGF1R protein, human)
RN  - 0 (Mitogens)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Somatomedin)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Endocrine Disruptors/*metabolism/pharmacology
MH  - Estrogen Receptor alpha/metabolism
MH  - Estrogen Receptor beta/metabolism
MH  - Female
MH  - Follicular Fluid/*chemistry
MH  - Granulosa Cell Tumor/etiology/*pathology
MH  - Granulosa Cells/drug effects/pathology
MH  - Humans
MH  - Mitogens
MH  - Ovarian Neoplasms
MH  - Receptor, IGF Type 1
MH  - Receptors, Estrogen/*analysis/metabolism/physiology
MH  - Receptors, G-Protein-Coupled/*physiology
MH  - Receptors, Somatomedin/*physiology
MH  - Young Adult
OTO - NOTNLM
OT  - G protein-coupled estrogen receptor 1
OT  - Granulosa tumors
OT  - Insulin-like growth factor 1 receptor
OT  - Persistent organic pollutant
EDAT- 2018/11/11 06:00
MHDA- 2019/02/05 06:00
CRDT- 2018/11/11 06:00
PHST- 2018/07/24 00:00 [received]
PHST- 2018/10/30 00:00 [revised]
PHST- 2018/11/02 00:00 [accepted]
PHST- 2018/11/11 06:00 [pubmed]
PHST- 2019/02/05 06:00 [medline]
PHST- 2018/11/11 06:00 [entrez]
AID - S0045-6535(18)32115-5 [pii]
AID - 10.1016/j.chemosphere.2018.11.018 [doi]
PST - ppublish
SO  - Chemosphere. 2019 Feb;217:100-110. doi: 10.1016/j.chemosphere.2018.11.018. Epub 
      2018 Nov 4.