Environmental polycyclic aromatic hydrocarbons mixture, in human blood levels, decreased oestradiol secretion by granulosa cells via ESR1 and GPER1 but not ESR2 receptor
| Autor: | Ewa L. Gregoraszczuk, Karolina Zajda |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Health Toxicology and Mutagenesis oestradiol 010501 environmental sciences Toxicology 01 natural sciences Cell Line Receptors G-Protein-Coupled gene silencing 03 medical and health sciences Internal medicine medicine Basic Helix-Loop-Helix Transcription Factors Gene silencing Estrogen Receptor beta Humans Oestradiol secretion Polycyclic Aromatic Hydrocarbons RNA Small Interfering Receptor AHR/ESR1/ESR2/GPER1 0105 earth and related environmental sciences Granulosa Cells Human blood Estradiol Chemistry Estrogen Receptor alpha General Medicine P450arom expression 030104 developmental biology Endocrinology Gene Expression Regulation Receptors Aryl Hydrocarbon Receptors Estrogen Environmental Pollutants Female Estrogen receptor alpha |
| Zdroj: | Humanexperimental toxicology. 39(3) |
| ISSN: | 1477-0903 |
| Popis: | Tissue-dependent oestrogenic and anti-oestrogenic activity of polycyclic aromatic hydrocarbons (PAHs) has been suggested. In this study, the effect of two PAH mixtures, M1 composed of all 16 priority pollutants and M2 composed of five (noted in the highest levels) compounds, on follicle-stimulating hormone receptor (FSHR) expression, basal or FSH-induced oestradiol (E2) secretion and aromatase cytochrome P450 (P450arom) protein expression, by non-luteinised human granulosa cell line (HGrC1) was determined. In addition, the consequences of gene silencing of oestrogen receptor alfa (siESR1), oestrogen receptor beta (siESR2) and a G protein-coupled receptor (siGPER1) on the above parameters were described. Neither PAH mixture had an effect on basal FSHR protein expression; however, both mixtures increased FSH-induced FSHR expression. Decreased E2 secretion and P450arom expression was also demonstrated. In both basal and FSH treated cells, siESR1 and siGPER1 reversed the inhibitory effect of the mixtures on E2 secretion; however, in siESR2 cells, the inhibitory effect was still observed. This study showed that both classic ESR1 and GPER1 were involved in the inhibitory effect of both PAH mixtures on E2 secretion and confirmed that expression of P450arom could be downregulated through the aryl hydrocarbon receptor and additionally through the ESR2. |
| Databáze: | OpenAIRE |
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