Impact of low concentrations of phthalates on the effects of 17β
Phthalates are widely used in our general life and are generally recognized as an endocrine disrupter because of their estrogenic and antiandrogenic activities. Therefore, whether or not phthalates play a role in steroid hormone-dependent cancers, such as breast cancer, has been strongly considered.
The Estrogenic Effects of Phthalates (DEHP, DBP) in MCF-7 Cell
To evaluate the estrogenic activities of di-ethyl hexyl phthalate (DEHP) and di-butyl phthalate (DBP), two phthalates known as endocrine disrupters, we used MCF-7 human breast cancer...
The phthalate DEHP modulates the estrogen receptors α and β
In addition, DEHP increased the S + G2M phases, Ki67 index and cyclin D1 in vitro, leading to a rise in the lactotroph and somatotroph cell populations. These results showed that DEHP modified the pituitary ERα and β expression in lactotrophs and somatotrophs from female rats and had an impact on the pituitary cell growth.
Lower concentrations of phthalates induce proliferation in
The present study demonstrates that, even at a very low concentration, BBP, DBP, and DEHP were not only still capable of inducing a proliferative effect through the PI3K/AKT signaling pathway but also displaying estrogenic activity. Therefore, the current reference doses for phthalates defined by go
Identification of estrogenic genes responding to phthalate esters
Total RNA was isolated from cells treated with each phthalate esters (BBP, DBP, and DEHP) and 17β-estradiol, and then changes of gene expression were analyzed using cDNA microarray (KISTCHIP-400). This microarray includes 416 endocrine related genes based on public database and research papers.
- How do DBP and DEHP affect reproductive toxicity of phthalates?
- Generally, it is thought that DBP and DEHP cause leydig cell aggregation and inhibit the production of testosterone as well as Insl-3 while their monoesters act as agonists of PPARα and PPARγ . Thus, several pathways are involved in reproductive toxicity of phthalates.
- Which phthalate has anti-estrogenic activity?
- Mono-n-pentyl phthalate, mono-cyclohexyl phthalate, mono-benzyl phthalate, mono-isopropyl phthalate & BBP have anti-estrogenic activities. DBP, BBP, & DHP exhibit weak ER-mediated activity in some of in vitro assays. The relative estrogenic potencies of these descended in the BBP > DBP > DIBP > DEP > DINP.
- Do low molecular weight phthalates affect sexual differentiation?
- These findings concluded that DEHP, BBP, and DINP altered sexual differentiation but DINP was less toxic than both. Thus, from the studies available it can be stated that low molecular weight phthalates produce least or no reproductive effects. C5-C10 chain phthalate esters were administered from GD6–15 at doses of 40, 200 and 1000 mg/kg.
- How does phthalate affect fetal resorption?
- In phthalate treated rats, embryopathy was manifested by 12–79% of fetal deaths and fetal resorptions. Fetotoxicity was expressed by a significant reduction in fetal weights. DMEP caused a congenital malformation of the brain i.e. hydrocephalus interna . Shiota et al. treated pregnant mice with DEHP and DBP in food GD0-parturition.
- Do phthalates bind to endocrine disruptors?
- Under in vitro condition, phthalates are not androgen receptor (AR) antagonists directly at concentrations of up to 10 μM, so phthalates and their metabolites do not bind to the AR . Endocrine disruptors (EDs) also act by altering the function of the hypothalamus-pituitary-gonadal (HPG) axis , .
- How do phthalate esters affect fetal testosterone synthesis?
- In the developing fetal testis, toxic phthalate esters target numerous pathways. In fetal leydig cells, molecular pathways associated with synthesis and transport of lipid and cholesterol and with steroidogenesis are reduced, which results in a reduction in testosterone synthesis.
