Additional effects of bisphenol A and paraben on the induction of calbindin-D(9K) and progesterone receptor via an estrogen receptor pathway in rat pituitary GH3 cells.

There are concerns about the combined estrogenic effects of chemicals since mixtures of these chemicals exist in our environment. This study investigated potential additional interactions between bisphenol A (BPA) and isobutylparaben (IBP), which are major xenoestrogens used in the manufacture of plastics, cosmetics, drugs, and other products. The combined effects of these two chemicals were analyzed by measuring the expression of calbindin-D(9k) (CaBP-9k) in rat pituitary cancer GH3 cells. GH3 cells were treated with single and combination doses of both chemicals (BPA single doses: 10(-7), 10(-6) and 10(-5) M; IBP single doses: 10(-7), 10(-6) and 10(-5) M, and each of the BPA and IBP doses combined). Prior to treatment, cells were temporarily transfected with a plasmid containing an ERE-luciferase reporter gene. Luciferase activity was measured as an indicator of ER activation by 17ß-estradiol (E2), BPA, and IBP. BPA (10(-5) M) combined with IBP (10(-7) M and 10(-6) M) induced a significant increase in the luciferase activity. Twenty-four hours after treatment, dose-dependent effects were observed in both single and combined dose groups, and several combination doses induced significant increases in the expression of CaBP-9k and progesterone receptor (PR) at both transcriptional and translational levels. Pre-treatment with ICI 182,780, a pure estrogen antagonist, significantly reversed BPA- and IBP-induced CaBP-9k and PR upregulation in GH3 cells. Taken together, these results indicate that BPA and IBP may have additionally increased estrogenic potency via an estrogen receptor-mediated pathway.

Synergistic effects of parabens on the induction of calbindin-D(9k) gene expression act via a progesterone receptor-mediated pathway in GH3 cells.

Although the endocrine-disrupting bioactivity of parabens is weakly estrogenic (parabens are xenoestrogens), their combined synergistic effect is unknown. The aim of this study was to investigate the effects of methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), isopropyl paraben (IPP), butyl paraben (BP), and isobutyl paraben (IBP), either alone or in combination (MP + EP + PP + BP; PP + IPP; and BP + IBP) on the induction of the estrogenic biomarker gene, calbindin-D(9k) (CaBP-9k), in rat pituitary lactosomatotrophic GH3 cells. The expression of CaBP-9k mRNA and protein was analyzed using real-time PCR and Western blot analysis, respectively. After 24 h of treatment, a significant increase in CaBP-9k expression was observed. This was dependent upon the length of the paraben alkyl chains (shortest in MP and longest in IBP). Interestingly, the synergistic effects of these paraben combinations were observed at a dose (10(-5) M) of these parabens, which induced the highest expression of CaBP-9k mRNA and protein. To investigate the involvement of estrogen receptors (ERs) and progesterone receptors (PRs), through which parabens exert their effects, the expression levels of ERα and PR-B were also examined. The expression of ERα mRNA and protein fluctuated after paraben treatment in GH3 cells, which was not significant. However, the expression level of ERα gene was induced when cotreated with 17ß-estradiol (E2) and ICI 182, 780 (estrogen receptor antagonist). The different combinations of parabens induced the expression of the PR-B gene, which was abolished by cotreatment with ICI 182,780. The expression patterns of CaBP-9k and PR-B genes appeared to be similar in response to paraben treatments. This implied that CaBP-9k expression in GH3 cells may be induced by parabens via a PR-mediated pathway. Taken together, these results suggest that exposure to multiple parabens at low concentrations may increase their synergistic estrogenic activities in GH3 cells through a PR-mediated pathway.

Regulation and molecular mechanisms of calcium transport genes: do they play a role in calcium transport in the uterine endometrium?

Maintenance of calcium (Ca) balance in the uterus is critically important for many physiological functions, including smooth muscle contraction during embryo implantation. Ca transport genes, i.e., transient receptor potential cation channel subfamily V members 5/6 (TRPV5/6), calbindins, plasma membrane Ca(2+)-ATPase 1 (PMCA1), and NCX1/NCKX3, may play roles in the uterus for Ca transport and reproductive function. Although these Ca transport genes may have a role in Ca metabolism, their role(s) and molecular mechanisms require further elucidation. In this review, we highlight the expression and regulation of Ca transport genes in the uterus to clarify their potential role(s). Since Ca transport genes are abundantly expressed in reproductive tissues in a distinct manner, they may be involved in specific uterine functions including fetal implantation, Ca homeostasis, and endometrial cell production.

A cellular automaton model of cancerous growth.

A cellular automaton model describing immune system surveillance against cancer is furnished. In formulating the model, we have taken into account the microscopic mechanisms of cancerous growth, such as the proliferation of cancer cells, the cytotoxic behaviors of the immune system, the mechanical pressure inside the tumor and so forth. The model may describe the Gompertz growth of a cancer. The results are in agreement with experimental observations. The influences of the proliferation rate of cancer cells, the cytotoxic rate and other relevant factors affecting the Gompertz growth are studied.