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 OFFSPRING

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 whet her a high-fat diet alters the number of estrogen receptor (ER) bindin g sites and protein kinase C (PKC) activity in the mammary gland of th ese animals, In the female offspring, the effects of maternal exposure to a high-fat diet during pregnancy on development of the mammary epi thelial tree were studied also. BALB/c mice were kept on a diet contai ning either 43% (high-fat) or 16% (low-fat) calories from corn oil, wh ich consists mostly of n-6 polyunsaturated fatty acids, for 1 month, I n adult female mice, a 6-fold increase in the number of ER binding sit es and 2-fold increase in PKC activity were found in the mammary gland s of the high-fat mice when compared with the low-fat mice, In pregnan t mice, a high-fat diet increased ER binding sites by 61% and PKC acti vity by 51%, In contrast to adult and pregnant mice, females exposed t o a high-fat diet only in utero through their pregnant mother exhibite d 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 10 0 days (44 and 20% decrease, respectively), The mammary epithelial tre e of the high-fat offspring contained more terminal end buds and was l ess differentiated than that of the low-fat offspring, These findings show that consumption of a high-fat diet increases ER and PKC in the a dult and pregnant mouse mammary gland, perhaps contributing to the fat -induced promotion of mammary tumorigenesis, In contrast, reduced ER a nd PKC following a high-fat exposure in utero may be associated with i ncreased susceptibility to carcinogenesis, possibly due to an increase d number of terminal end buds that are the sites of neoplastic transfo rmation in the mammary gland.