Cadmium Increases Cell Proliferation in Anterior Pituitary Cells

MILER EA, CABILLA JP, QUINTEROS AF, NUDLER SI, RONCHETTI SA, DUVILANSKI BH

Washington, DC-USA

Congreso; The Endocrine Society's 91st Annual Meeting; 2009

The Endocrine Society

Cadmium (Cd 2+) is one of the most toxic transition metal, associated with air and water pollution, as well as cigarette. Recent reports have highlighted the potential of Cd 2+ to mimic the effects of estrogen in various tissues, acting as an endocrine disrupter. The aim of our studies was to evaluate whether Cd 2+ could stimulate anterior pituitary gland cells proliferation in vitro. Materials and Methods: Anterior pituitary cultures from young-adult female rats were used. Experiments were performed in phenol red-free Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% charcoal stripped fetal bovine serum. Cells were incubated with Cd 2+ or vehicle (control) for 72 to 96 h. Proliferation assay was evaluated by BrdU incorporation (added during the last 24 h) by immunocytochemistry. Cyclin D1 and cyclin D3 expression were studied by semi-quantitative PCR using GAPDH as internal control. 17b-estradiol (1 nM) was used as positive control of the experiments. Results: Cd 2+ (10 nM) increased basal proliferation at 96 h (Control: 23.8% + 2.2;    Cd 2+: 45.5% + 2.7, p<0.05). In parallel with cell proliferation, Cd 2+ treatment for 72 h significantly increased cyclin D1 and cyclin D3 mRNA levels (relative expression of cyclin D1: Control: 2.99 + 0.04; Cd 2+: 3.74 + 0.16 p<0.05 and cyclin D3: Control: 2.49 + 0.01; Cd 2+: 4.00 + 0.07, p<0.001). Similar results were found in rat lactosomatotroph cell line GH3. Conclusions: These findings showed for the first time that Cd 2+ has an estrogen-like activity in pituitary gland cells, increasing cell proliferation. This result was confirmed by an enhanced expression of both cyclin D1 and cyclin D3. Therefore, this heavy metal at low concentrations could increase cell proliferation in estrogen-responsive tissues and that could be another cause of tumor growth.