Rat strain specific attenuation of estrogen action in the anterior pituitary gland by dietary energy restriction.
The purpose of this study was to compare the effects of a 40% restriction of dietary energy consumption, relative to that consumed by rats allowed to feed ad libitum, on the ability of 17beta-estradiol (E2) to induce pituitary tumorigenesis in two inbred rat strains, ACI and Copenhagen (COP), which are very closely related genetically. Ovary-intact ACI and COP rats were fed either a control or an energy-restricted diet beginning at 8 wk of age. Continuous treatment with E2, released from subcutaneous Silastic tubing implants, was initiated at 9 wk of age and the animals were killed 12 wk later. Estrogen-induced pituitary tumorigenesis is associated with rapid induction of lactotroph hyperplasia, increased pituitary mass, and hyperprolactinemia. E2 significantly increased pituitary mass and circulating prolactin (PRL) in both ACI and COP rats, and this response was significantly greater in ACI rats relative to COP. Dietary energy restriction did not inhibit E2-induced pituitary growth in the ACI rat. By contrast, E2-induced pituitary growth in COP rats was attenuated by dietary energy restriction, as evidenced by quantification of pituitary mass, pituitary weight to body weight ratio, circulating PRL, and pituitary cell proliferation. This study indicates that sensitivity to the inhibitory actions of dietary energy restriction on E2-induced pituitary tumorigenesis is genetically determined.
Harvell
Djuana M E
DM
Eppley Institute for Research in Cancer, and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Buckles
Linda K
LK
Gould
Karen A
KA
Pennington
Karen L
KL
McComb
Rodney D
RD
Shull
James D
JD
D000818:Animals; D031204:Caloric Restriction; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000473:pathology; D002149:Energy Intake; D004958:Estradiol / Q000009:adverse effects*; D005260:Female; D006966:Hyperprolactinemia / Q000139:chemically induced; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D013045:Species Specificity
D004958:Estradiol; D011388:Prolactin