[Inhibitory effects of melatonin on the development of 17-beta-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-beta-estradiol (E(2)) in vivo. The prolactinomas were established by implanting E(2)-laden silastic capsules subcutaneously in Sprague-Dawley male rats weighing 80 approximately 100 g. Melatonin (0.05, 0.25, 0.50, 1.00, and 2.00 mg/0.1 ml/rat) was administrated subcutaneously at l8:00 h for 90 days, beginning from d 7 prior to tumor induction. Controls were given equal volumes of 4 percent; alcohol in 0.9 percent; 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 delta233/ml respectively. (2) The correlation coefficients between tumor weight and plasma PRL content, tumor weight and plasma peroxidative lipid content, and plasma PRL content and plasma peroxidative 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 E(2)-induced prolactinoma and the secretion of PRL in comparison with the matched control. (2) The levels of 0.05 approximately 2.00 (P<0.05 approximately 0.00l) 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 peroxidative 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 E(2)-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.

[Inhibitory effect of melatonin on the development of pituitary prolactin-producing tumors induced by 17-beta-estradiol].

OBJECTIVE: To examine the inhibitory effect of melatonin (MLT) on the development of pituitary prolactin-producing tumors (prolactinoma) induced by 17-beta-estradiol (E2), in vivo, and explore MLT's oncostatic mechanisms. METHODS: The prolactinomas were established by implanting E2-laden silastic capsules subcutaneously in Sprague-Dawley male rats. MLT doses 0.05, 0.25, 0.50, 1.00, and 2.00 mg/rat were administrated separately to 5 groups subcutaneously starting seven days prior to tumor induction for 97 days. The matched controls were given equal volumes of 4% alcohol in saline. RESULTS: (1) The prolactinoma weights in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 25.91% (P > 0.05), 48.78% (P < 0.01), 36.78% (P < 0.05), 31.04% (P > 0.05) and 35.22% (P > 0.05) respectively which were lower than that of control group; (2) The PRL mRNA levels of prolactinoma in 0.05, 0.25, and 0.50 mg MLT dose groups were 33.67% (P < 0.05), 25.51% (P < 0.05) and 41.84% (P < 0.01) respectively which were lower than that of control group as estimated by Northern Blot, and the in situ hybridization studies; (3) The DNA contents of prolactinoma in 0.05, 0.25 and 0.50 mg MLT dose groups were 40.73% (P < 0.001), 51.15% (P < 0.001) and 60.23% (P < 0.001) respectively which were lower than that of control group by laser scanning confocal microscopy; (4) Plasma peroxidative lipid contents in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 26.45% (P < 0.05), 23.97% (P < 0.05), 47.11% (P < 0.001), 66.12%(P < 0.001) and 64.46% (P < 0.001) respectively which were lower than that of control group. The correlation coefficient between MLT doses and plasma peroxidative lipid contents was -0.8257 (P < 0.05). CONCLUSIONS: MLT in suitable doses is able to inhibit the development of E2-induced prolactinoma by inhibiting the expression of PRL gene and the DNA synthesis. The link between MLT antioxidative action and its inhibitory effect on development of prolactinoma should be further investigated.

[The effects of gastrin-releasing peptide (GRP) and vasoactive intestinal polypeptide (VIP) on the prolactin (PRL) gene transcription of pitutitary PRL releasing tumor of rat].

The effects of gastrin-releasing peptide (GRP) and vasoactive intestinal polypeptide (VIP) on the prolactin gene transcription of cultured pituitary of male Sprague-Dawley (SD) rats PRL releasing tumor (PPRT) (induced by estradiol) cells were studied. The PRL mRNA levels were determined by in situ hybridization of cytoplasmic RNA with a DIG-labeled PRL cDNA probe. PRL mRNA levels didn't change when the PPRT cells were incubated with 10(-8) mol/L or 10(-7) mol/L GRP for 24 h, but decreased by 20% when GRP was increased to 10(-6) mol/L (P < 0.05). The PRL mRNA level increased to 1.60, 2.10, 2.21 times of the control group when the PPRT cells were respectively incubated with 10(-8), 10(-7), 10(-6) mol/L VIP for 24 h (P < 0.05). The PRL mRNA level didn't change when the PPRT tumor cells were incubated with 10(-8) mol/L E2 for 48 h, but did increase to 2.80 and 2.92 times of the control group respectively when 10(-7) mol/L and 10(-6) mol/L E2 were used. The results above indicated that GRP and VIP exert an inhibitory and a stimulatory effect on RPL gene transcription respectively, while the stimulatory action of E2 on PRL secretion is a direct one.

[Regulatory role of galanin on prolactin and beta-endorphin release from anterior pituitary lobe of rat].

The role of brain-gut peptide galanin in the regulation of prolactin (PRL) and beta-endorphin (beta-EP) release from anterior pituitary lobe was studied in vivo in conscious male rats and in vitro with cultured anterior pituitary cells of the rat. Galanin (1 microgram or 3 micrograms/rat) injected into the third cerebral ventricle of rats produced highly significant, dose-related increases of PRL resting secretion, but did not alter resting secretion of beta-EP and restraint stress-induced release of PRL and beta-EP. However, galanin (0.05, 0.5 and 1.0 micrograms/5 x 10(5) cells.ml-1) induced highly significant, dose-related increase of beta-EP secretion from dispersed anterior pituitary cells, but failed to alter significantly PRL secretion from the cultured cells. These results indicate that central galanin has a stimulatory role in pituitary PRL resting secretion via the hypothalamus, whereas peripheral galanin stimulates beta-EP secretion only via direct action of this peptide in anterior pituitary cells.