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Fig. 1.Immunohistochemical stain-ing of female Wistar rat anteriorpituitary gland for expression ofPRL, VEGF, MMP-9, and AQP-1.V-vehicle control rats, DES-diehyl-stilbestrol treated rats, DES+M-diehylstilbestrol treated rats coad-ministrated with melatonin. scalebars=30µm.
group, possibly attributed to the sharp withdrawal ofproliferated cells.
The H+E staining-based evaluation scores in thevehicle, DES, and DES + melatonin groups were1.42±1.13, 4.57±0.98, and 2.00±0.63, respectively,and frequency distribution of values in each groupwere in agreement with normal distribution. Long-term treatment of DES significantly increased the H+Escore, which was reduced by subcutaneous injection ofmelatonin (p<0.01 vs. DES group). In the sole pituitarywith spontaneous tumor-like changes, the tumor-likecells were closely packed with similar cytoplasmic andnuclear volumes, suggesting that they were from thesame origin.
blood vessels. By contrast, administration of DES ledto extensive expression of VEGF in the cytoplasm ofpituitary cells, accompanied by angiogenesis, whichwas reduced by melatonin at a dose of 1 mg/day for 4weeks (Fig. 1).
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