Sinica Inhibitory effects of melatonin on the development of 17-β-estradiol induced prolactinoma in relation to plasma prolactin and peroxidative lipid contents

In the present study, we have examined inhibitory effects of melatonin on the development of pituitary prolactin-producing tumors (prolactinoma) induced by 17-β-estradiol (E₂) in vivo. The prolactinomas were established by implanting E₂-laden silastic capsules subcutaneously in Sprague-Dawley male rats weighing 80-100 g. Melatonin (0.05, 0.25, 0.50, 1.00, and 2.00 mg/0.1 ml/rat) was administrated subcutaneously at 18:00 h for 90 days, beginning from d 7 prior to tumor induction. Controls were given equal volurnes of 4% alcohol in 0.9% saline.Our results showed: (1) In control group and groups given respectively 0.05, 0.25, 0.50, 1.00 and 2.00 mg melatonin, the weight of prolactinoma was 115.0 ± 71.0, 85.2 ± 41.0, 58.9 ± 24.1, 72.7 ± 23.6, 79.3 ± 56.1, 74.5 ± 46.8 mg respectively; the plasma prolactin (PRL) content was 493.46 ± 33.3, 373.78 ± 26.5, 125.13 ± 13.3, 201.79 ± 11.2, 418.88 ± 41.3, 281.94 ± 36.4 ng/ml respectively; the plasma peroxidative lipid content was 1.21 ± 0.23, 0.89 ± 0.32, 0.92 ± 0.27, 0.64 ± 0.24, 0.41 ± 0.14 and 0.43 ± 0.21 △D233/ml respectively. (2) The correlation coefficients between tumor weight and plasma PRL content, tumor weight and plasma peroxydative lipid content, and plasma PRL content and plasma peroxydative lipid content were 0.8738, 0.5550 and 0.2141 respectively. These results indicate: (1) The dosages of 0.25 (P < 0.01) and 0.50 (P < 0.05) mg, but not 0.05 (P > 0.05), 1.00 (P > 0.05) and 2.00 (P > 0.05) mg, melatonin significantly inhibited the development of the E₂-induced prolactinoma and the secretion of PRL in comparison with the matched control. (2) The levels of 0.05-2.00 (P < 0.05-0.001) mg melatonin showed a dose-dependent antioxidative action. (3) There are positive correlation between tumor weight and plasma PRL content (P < 0.05), but no correlation between tumor weight and plasma peroxydative lipid content (P > 0.05), and plasma PRL content and plasma peroxidative lipid content (P > 0.05) . Therefore, our experiments demonstrate that the inhibition of the development of E₂-induced prolactinoma by adequate dosage of melatonin may be related to the inhibitory effects of MLT on the secretion of PRL, but not to the antioxidative action of MLT.