There are suspected links between an animal's diet, differentiation status of a target tissue, and sensitivity to chemically induced
cancer. We have demonstrated that rats fed AIN93G diets made with
soy protein isolate (SPI) or
whey protein hydrolysate (WPH) had a lower incidence of
7,12-dimethylbenz(a)anthracene (DMBA)-induced
adenocarcinoma than rats fed the same diet made with
casein (CAS). The current study was conducted to determine the differentiation status of the mammary glands during development. Offspring of rats (n = 5-10/group) were fed diets made with SPI, WPH, or CAS throughout life (beginning on gestation day 4) and were sacrificed on postnatal day (PND) 21, PND 33, PND 50 or on metaestrous between PND 48 and PND 51. There were no significant differences between the numbers of mammary terminal end buds (TEBs) or lobuloalveoli (LOB) between any of the diets groups at PND 21 or PND 33, but at PND 50 there was an 75% decrease in the mean numbers of TEBs/mm(2) in the SPI- or WPH-fed rats, compared with the CAS-fed rats (p = 0.09 and p = 0.06, respectively). In rats sacrificed in metaestrous, there were no significant differences in the proliferation index (PI) in the TEBs or LOB between any of the diet groups. In metaestrous rats, there were twice as many cells expressing
estrogen receptor beta (
ERbeta; approximately 60%) compared with
estrogen receptor alpha (
ERalpha; approximately 30%) in the LOB and 1.5 times more
ERbeta (approximately 60%) compared with
estrogen receptor alpha (
ERalpha, approximately 40%) in the TEBs. There were no diet-dependent differences in expression of
ERalpha and
ERbeta. Similarly, there were no differences between the diet groups in
progesterone receptor (PR) expressing LOB cells. However, in the TEBs there was a diet-dependent difference in PR positive cells with a 34% increase (p < 0.05) in the SPI-fed rats and a 38% increase (p < 0.05) in the WPH-fed rats compared with the CAS-fed rats. These results show that the type of
dietary protein alters the phenotype of mammary epithelia in the TEBs. The SPI- and WPH-dependent changes in mammary differentiation may contribute to the reduced sensitivity to DMBA-induced
mammary cancer in rats fed these
proteins.