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Consumption of a High-Fat Diet Alters Estrogen Receptor Content, Protein Kinase C Activity, and Mammary Gland Morphology in Virgin and Pregnant Mice and Female Offspring¹

Lombardi Cancer Center [L. H-C., A. S., M. R., M. M.], Departments of Psychiatry [L. H-C., M. R.] and Biochemistry and Molecular Biology [A. S., M. M.], Georgetown University, Washington, DC 20007

Previous studies have shown that a diet high in polyunsaturated fatty acids increases mammary tumor incidence in adult and pregnant mice and rats and in the female offspring. The present study investigated whether a high-fat diet alters the number of estrogen receptor (ER) binding sites and protein kinase C (PKC) activity in the mammary gland of these animals. In the female offspring, the effects of maternal exposure to a high-fat diet during pregnancy on development of the mammary epithelial tree were studied also. BALB/c mice were kept on a diet containing either 43% (high-fat) or 16% (low-fat) calories from corn oil, which consists mostly of n-6 polyunsaturated fatty acids, for 1 month. In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice. In pregnant mice, a high-fat diet increased ER binding sites by 61% and PKC activity by 51%. In contrast to adult and pregnant mice, females exposed to a high-fat diet only in utero through their pregnant mother exhibited a significantly reduced number of mammary ER binding sites by age 45 days (78% decrease) and a reduction in PKC activity by ages 30 and 100 days (44 and 20% decrease, respectively). The mammary epithelial tree of the high-fat offspring contained more terminal end buds and was less differentiated than that of the low-fat offspring. These findings show that consumption of a high-fat diet increases ER and PKC in the adult and pregnant mouse mammary gland, perhaps contributing to the fat-induced promotion of mammary tumorigenesis. In contrast, reduced ER and PKC following a high-fat exposure in utero may be associated with increased susceptibility to carcinogenesis, possibly due to an increased number of terminal end buds that are the sites of neoplastic transformation in the mammary gland.

¹ This work was supported by Grant CN-80420 from the American Cancer Society, grants from the Cancer Research Foundation of America and the Lombardi Cancer Center Shared Animal Resource Facility, and USPHS Grant 2P30-CA51008.

² To whom requests for reprints should be addressed, at Lombardi Cancer Center, Research Building, Room W405, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20007-2197. Phone: (202) 687-7237; Fax: (202) 687-7505.

Received 6/ 5/97. Accepted 12/15/97.

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