Leydig cell tumorigenesis - implication of G-protein coupled membrane estrogen receptor, peroxisome proliferator-activated receptor and xenoestrogen exposure. In vivo and in vitro appraisal
E. Gorowska-Wojtowicz , M. Duliban , M. Kudrycka , P. Dutka , P. Pawlicki , A. Milon , B. Zarzycka , W. Placha , Małgorzata Kotula-Balak , A. Ptak , J.K. Wolski , B. Blińska
AbstractThe etiology and molecular characteristics of Leydig cell tumor (LCT) are scarcely known. From the research data stems that estrogen can be implicated in LCT induction and development, however it is not investigated in detail. Considering the above, herein we analyzed the relation between G-protein coupled membrane estrogen receptor, peroxisome proliferator-activated receptor and insulin-like family peptides (insulin-like 3 peptide; INSL3 and relaxin; RLN) expressions as well as estrogen level with impact of xenoestrogen (bisphenol A; BPA, tetrabromobisphenol A; TBBPA, and tetrachlorobisphenol A; TCBPA). While in our previous studies altered GPER-PPAR partnership was found in human LCT being a possible cause and/or additionally effecting on LCT development, here mouse testes with experimentally induced LCT and mouse tumor Leydig cell (MA-10) treated with BPA chemicals were examined. We revealed either diverse changes in expression or co-expression of GPER and PPAR in mouse LCT as well as in MA-10 cells after BPA analogues when compared to human LCT. Relationships between expression of INSL3, RLN, including co-expression, and estrogen level in human LCT, mouse LCT and MA-10 cells xenoestrogen-treated were found. Moreover, involvement of PI3K-Akt-mTOR pathway or only mTOR in the interactions of examined receptors and hormones was showed. Taken together, species, cell of origin, experimental system used and type of used chemical differences may result in diverse molecular characteristics of LCT. Estrogen/xenoestrogen may play a role in tumor Leydig cell proliferation and biochemical nature but this issue requires further studies. Experimentally-induced LCT in mouse testis and MA-10 cells after BPA exposure seem to be additional models for understanding some aspects of human LCT biology.
|Journal series||Tissue & Cell, [Tissue and Cell], ISSN 0040-8166, (N/A 40 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||Bisphenol, A G-protein coupled estrogen receptor, Insulin-Like peptides, Estrogen, Peroxisome proliferator-activated receptor, Leydig cell tumor|
|ASJC Classification||; ;|
|Publication indicators||: 2017 = 0.555; : 2018 = 1.553 (2) - 2018=1.447 (5)|
|Finansowanie||This work was supported by a grant OPUS12 2016/23/B/NZ4/01788 from National Science Centre, Poland.|
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