Long-term treatment with bromocriptine inhibits endometrial adenocarcinoma development in rats.
The effects of long-term blockade of prolactin (PRL) action by bromocriptine (BRC) treatment on uterine carcinogenesis and on related ovarian physiology were investigated using a rat uterine cancer model. Ten-week-old cycling female Donryu rats, a high yield strain for uterine corpus tumors (endometrial adenocarcinomas), were treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), as a tumor initiator, and injected with 1 mg/kg body weight BRC subcutaneously 4 times per week until 14.5 months of age to block the proestrus PRL surge. The study was terminated at 15 months of age, and the results showed that long-term BRC treatment significantly inhibited endometrial adenocarcinoma development in terms of both incidence (34.6% to 13.0% with significant difference at 5%) and multiplicity (0.35 to 0.18 with significant difference at 5%), which indicates the number of adenocarcinomas per animals. While BRC did not affect estrous cyclicity in the treated animals, a significant decline was evident in the serum 17 beta-estradiol (E2) to progesterone (P) ratio (E: P ratio), and the serum E2 level showed a decreased tendency at 15 months of age. While the precise pathway to the inhibitory effect could not be determined; the pathway by which ovarian hormonal imbalance decreases the serum E: P ratio most likely plays a crucial role.
Yoshida
Midori
M
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. midoriy@nihs.go.jp
Watanabe
Gen
G
Suzuki
Tomo
T
Inoue
Kaoru
K
Takahashi
Miwa
M
Maekawa
Akihiko
A
Taya
Kazuyoshi
K
Nishikawa
Akiyoshi
A
D000230:Adenocarcinoma / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D002273:Carcinogens; D016889:Endometrial Neoplasms / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006651:Histocytochemistry; D006727:Hormone Antagonists / Q000494:pharmacology; D007265:Inhibins / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood; D051381:Rats
D002273:Carcinogens; D006727:Hormone Antagonists; D008769:Methylnitronitrosoguanidine; D001971:Bromocriptine; C013525:ENNG; D011374:Progesterone; D004958:Estradiol; D007265:Inhibins; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone