Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells

Fortunati, Nicoletta; Guaraldi, Federica; Zunino, Valentina; Penner, Federica; D’Angelo, Valentina; Zenga, Francesco; Giraldi, Francesca Pecori; Catalano, M.; Arvat, Emanuela

doi:10.1016/j.envres.2017.07.015

Cited by 19 publications

(15 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A shows a reduction of ZAC1 gene expression by the combined treatment of both 10 and 100 nM OCT with BZ (vs OCT alone: 0.23 fold, and 0.24 fold, respectively; vs control: 0.20 fold, and 0.26 fold, respectively). BZ alone, as expected (Fortunati et al, 2017), did not modify ZAC1 gene expression. At protein level, western blot (Fig.…”

Section: Gh Gene Expression and Secretionsupporting

confidence: 70%

“…First, BZ reduced the efficacy of OCT in inhibiting GH3 cell proliferation. In this cell line model, BZ used alone had no effect on cell viability (Fortunati et al 2017), but other studies conducted in normal rat pituitary primary cells showed an increased cell viability and proliferation induced by this chemical (Tapella et al 2016), indicating that the effects can depend on cell type. GH gene expression was not modified by OCT alone; exposure to BZ increased GH mRNA levels and this effect persisted also in cells treated with BZ and OCT.…”

Section: Discussionmentioning

confidence: 61%

“…Based on our recent study (Fortunati et al 2017), showing the ability of some common pollutants to modify the behavior of pituitary adenoma cells and the expression of molecules involved in the somatostatin signaling, this study aimed to evaluate the influence of benzene (BZ) on the somatostatin analogue octreotide (OCT) in the treatment of GH-secreting pituitary adenomas.…”

Section: Discussionmentioning

confidence: 99%

“…The experimental dose (130 pM) was within ranges observed in blood of exposed people (Hines at al. 2009, Yan et al 2009, Hays et al 2012, Chovancova et al 2012) and as previously assessed in our recent study (Fortunati et al 2017). Octreotide (OCT) was kindly provided by Novartis Pharma AG (Basel, Switzerland).…”

Section: Chemicalsmentioning

confidence: 95%

“…Furthermore, our recent study (Fortunati et al 2017) demonstrated that some common chemical pollutants are able to induce modifications in molecules related to GH secretion and somatostatin signaling pathway, focusing on their capacity of enhancing aggressiveness and modifying biological behavior of pituitary tumors. Effects observed on ZAC1 and SSTR2 may imply an important role in sensitivity of pituitary adenomas to medical treatment.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Benzene affects the response to octreotide treatment of growth hormone secreting pituitary adenoma cells

Zunino

Catalano

Zenga³

et al. 2019

Environmental Research

Self Cite

View full text Add to dashboard Cite

Growth hormone (GH) secreting pituitary adenomas are the main cause of acromegaly. Somatostatin analogs are the gold standard of medical therapy; however, resistance represents a big drawback in acromegaly management. We recently demonstrated that benzene (BZ) modifies the aggressiveness of GH-secreting rat pituitary adenoma cells (GH3), increasing GH secretion and altering the synthesis of molecules involved in the somatostatin signaling pathway. Based on these pieces of evidence, this study aimed to evaluate the effects of BZ on octreotide (OCT) efficacy in GH-secreting adenoma cells. In GH3 cells, BZ counteracted the anti-proliferative action of OCT. GH gene expression, unmodified by OCT, remained high in BZ-treated cells as well as after treatment with the association of both. GH secretion, reduced by OCT, was increased after treatment with BZ alone or when the pollutant was used with OCT. The combination of BZ and OCT greatly reduced the gene expression of ZAC1 and SSTR2; and this reduction was also present at a protein level. BZ caused an increase in the protein level of the transcription factor STAT3 and in its phosphorylated form. In the presence of BZ, OCT lost the ability to reduce the phosphorylated protein levels. Finally, in primary cultures of human pituitary adenoma cells, BZ caused an increase in GH secretion. OCT decreased GH secretion, but the addition of BZ reversed the OCT effect. In conclusion, our results suggest that BZ may have an important role in the resistance of pituitary adenomas to the pharmacological treatment with somatostatin analogs.

show abstract

Section: Gh Gene Expression and Secretionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%