Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats

: The in vivo effects of melatonin on proliferation and apoptosis of 17‐β‐estradiol (E2)‐induced pituitary prolactin‐secreting tumor (prolactinoma) were investigated in rats kept in 12 L/12 D (lights on: 06:00–18:00 hr). As melatonin was shown to induce apoptosis of breast and liver tumor cells, we examined whether melatonin would induce apoptosis of rat pituitary prolactinoma cells. 0.125, 0.25, 0.50 or 1.0 mg melatonin/day/rat was administrated subcutaneously at 17:30–18:00 hr. The weight of prolactinomas was measured. Apoptosis was evaluated using the TdT‐mediated dUTP nick‐end labeling method. It was found that treatment with 0.25 and 0.50 mg melatonin for 97 days inhibited prolactinoma cell proliferation and increased prolactinoma cell apoptosis. Furthermore, melatonin induced mRNA expression of Bax and cytochrome c protein expression. Conversely, mRNA expression of Bcl‐2, and mitochondrial membrane potential were inhibited by melatonin treatment. These results suggest that melatonin inhibits the proliferation and induces apoptosis of rat pituitary prolactin‐secreting tumor via perturbation of mitochondria physiology.