title: Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats.
abstract: The in vivo effects of melatonin on proliferation and apoptosis of 17-beta-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.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Quan-Hui
authors.initials: QH
authors.lastname: Yang
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Xu
authors.forename: Rong-Kun
authors.initials: RK
authors.lastname: Xu
authors.forename: Shiu-Fun
authors.initials: SF
authors.lastname: Pang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol; D020287:In Situ Nick-End Labeling; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000178:diet therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D004958:Estradiol; D011388:Prolactin; D008550:Melatonin