Melatonin modulates the effects of diethylstilbestrol (DES) on the anterior pituitary of the female Wistar rat.
We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)-treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly allocated into three groups: vehicle control rats, DES-treated rats, and DES-treated rats co-administrated with melatonin beginning at week 13. At the end of 16 weeks, rats were weighed and decapitated for morphological studies, including an H+E staining-based score evaluation in regard to cell proliferation, angiogenesis, immunostaining for VEGF, MMP-9, and AQP-1, and electron microscopy. Compared with vehicle, long-term treatment of DES significantly reduced rat body weight and increased H+E score, both of which were counteracted by melatonin. Administration of melatonin also reduced the expression of VEGF and MMP-9, although no changes were detected in AQP-1 expression. In rats cotreated with melatonin, the RER loosened and accumulated more secretion granules. We thus concluded that melatonin can modulate the effects of DES on the rat anterior pituitary by downregulating expression of VEGF and MMP-9 and suppressing the release of secretion granules, suggesting a therapeutic potential in estrogen-induced pituitary malfunctions.
Zhao
Weijiang
W
Neuroscience Center, Shantou University Medical College, Shantou, Guangdong Province 515041, China Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Shi
Zhongfang
Z
Yuan
Fang
F
Li
Guilin
G
Sun
Yilin
Y
Zhang
Yazhuo
Y
Wang
Zhongcheng
Z
D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004054:Diethylstilbestrol / Q000378:metabolism / Q000494:pharmacology*; D018870:Endoplasmic Reticulum, Rough / Q000648:ultrastructure; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C496022:Aqp1 protein, rat; D004968:Estrogens, Non-Steroidal; D042461:Vascular Endothelial Growth Factor A; D051398:Aquaporin 1; D004054:Diethylstilbestrol; D020780:Matrix Metalloproteinase 9; D008550:Melatonin