Effects of prolactin and estrogen on cell proliferation of the mouse liver induced by partial hepatectomy.
Estrogen or prolactin suppresses mouse hepatocellular tumorigenesis induced by carcinogens through inhibition of the growth of preneoplastic hepatocytes. In the present study, we investigated whether estrogen or prolactin inhibits proliferation of normal hepatocytes as well as preneoplastic hepatocytes in mice. The proliferation of mouse hepatocytes was induced by partial hepatectomy, and DNA synthesis of the liver was evaluated by measurement of 5-[125I]iododeoxyuridine ([125I]IdUrd) uptake/mg liver DNA after an injection of [125I]IdUrd into mice. For acute treatment with estrogen or prolactin, estradiol-17 beta (E2) (1 micrograms) or ovine prolactin (140 micrograms) was injected into ovariectomized mice twice a day from the day of partial hepatectomy. For chronic treatment with estrogen, ovariectomized mice received implants of E2 pellets containing 100 micrograms E2 40 days before partial hepatectomy, and for chronic treatment with prolactin, hyperprolactinemia was induced by pituitary graft under the renal capsule of ovariectomized mice 40 days before partial hepatectomy or by daily injections of perphenazine (150 micrograms/day) beginning 40 days before partial hepatectomy. The acute treatment with either estrogen or prolactin did not affect the hepatocyte proliferation induced by partial hepatectomy. Chronic hyperprolactinemia induced by the pituitary graft or by injections of perphenazine, and the chronic treatment with E2 pellets did not suppress either basal or partial hepatectomy-induced proliferation of hepatocytes. The present results show that acute and chronic treatments with estrogen or prolactin do not inhibit proliferation of mouse normal hepatocytes, and suggest that the effects of estrogen and prolactin on proliferation of mouse hepatocytes are different from those on proliferation of preneoplastic hepatocytes.
Takada
T
T
Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Yamamoto
T
T
Koike
K
K
Kanda
Y
Y
Miyake
A
A
Sugihara
A
A
Tsujimura
T
T
Terada
N
N
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006498:Hepatectomy; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011388:Prolactin / Q000008:administration & dosage*
D004958:Estradiol; D011388:Prolactin; D004247:DNA