The effect of ethanol consumption on the development of the female rat mammary gland

When sexually immature and sexually-mature female rats were chronically exposed to ethanol-containing diets mammary gland TEB density increased and the density of AVB was decreased. An increase in TEB structures is representative of an undifferentiated gland and are considered susceptible to chemical carcinogen action. Similarly, in the sexually-mature carcinogen-treated (NMU) rat, consumption of dietary ethanol was associated with a significant increase in carcinogen-sensitive TEB and TD structures and a concomitant decrease in carcinogen-insensitive AVB structures. In addition, normal mammary gland TEB DNA-LI also was increased at 20% and 30% ethanol calories. Furthermore, in the NMU-treated rat the mammary gland TEB responded to consumption of ethanol by increasing their DNA-LI. In that 80% to 90% of TEB were in a higher labeling index range between 20 to 35 for the ethanol-fed rats as compared to a range of 12 to 16 for both the control diet fed groups. Dietary restriction had a separate effect on mammary development. TEB density was not affected but AVB density was significantly decreased in response to dietary restriction. The TEB DNA-LI for the diet restricted rats was also not significantly different from the ad-libitum control-fed rats. Circulating hormone levels of estrogen $\rm (E\sb2)$ and progesterone $\rm (P\sb4)$ in the immature and mature female rat after ethanol intake resulted in a significant decrease in serum $\rm P\sb4$ compared to ad libitum-fed and pair-fed controls, whereas serum $\rm E\sb2$ was unaffected by ethanol. Between 35 and 55 days of age, the mammary epithelium of the immature female rat undergoes dramatic changes as structures representative of the immature gland (TEB) differentiate into structures (AVB) characteristic of the more mature gland. Progesterone is required for the maturation of the mammary epithelium and the decrease in serum progesterone measured for rats fed ethanol may contribute in part to the changes in densities of TEB and AVB that were observed. Since steroid hormones have a significant role in regulating mammary cell proliferation within the target cells, mammary gland $\rm E\sb2$ receptor content $\rm (E\sb2R)$ and binding affinity were evaluated. It was found that ethanol at 20% of calories increased total and occupied nuclear receptor content compared to isocaloric controls. Although nuclear receptor content was not affected by increased concentration of ethanol, the content of cytosolic $\rm E\sb2R$ was affected as ethanol calories increased. At 20% of calories, the unoccupied $\rm E\sb2R$ content was enhanced, while at 30% of calories occupied receptor content was reduced. For the diet-restricted rats, overall receptor content was reduced compared to ad-libitum controls. The cytosolic receptor binding affinity (Ka) was increased for ethanol-fed rats at 30% of calories, thus indicating enhanced affinity or tight binding of $\rm E\sb2$ for its receptor. Overall, these results suggest that mammary gland development and differentiation can be modified by dietary ethanol intake. These changes in the mammary gland morphology in response to ethanol are mediated in part by changes in the circulating concentration of serum $\rm P\sb4$ as well as by local alterations in the quantity of binding affinity of mammary cytosolic estrogen receptors. (Abstract shortened by UMI.)U of I OnlyETDs are only available to UIUC Users without author permissio