[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.
Gao
L
L
Department of Physiology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China. gaolie@ht.rol.cn.net
Xu
R K
RK
Pang
C S
CS
Xu
J P
JP
Shan
H M
HM
Pang
S F
SF
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004958:Estradiol; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D015175:Prolactinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D004958:Estradiol; D004247:DNA; D008550:Melatonin