Mammary gland differentiation by early life exposure to enantiomers of the soy isoflavone metabolite equol
The role of soy in reducing breast cancer risk has been suggested to be associated with early exposure to isoflavones, which alter mammary gland morphology. The objective of the study was to determine the effect of dietary exposure to the enantiomers of a key soy isoflavone metabolite, equol, on mammary gland development and later chemoprotection using the DMBA-induced animal model of breast cancer. Animals were exposed to S-(-)equol or R-(+)equol (250 mg/kg diet) during the neonatal (0-21 days) or prepubertal (21-35 days) periods only. Histological evaluation of the mammary glands showed that both enantiomers fed neonatally via the dam led to significant precocial mammary gland differentiation. By day 50, early S-(-)equol or R-(+)equol exposure resulted in a decrease in immature terminal end structures and an increase in mature lobules, suggesting an early 'imprinting' effect. Despite these morphological changes to the mammary gland, neonatal and prepubertal exposure to equol had no long-term chemoprevention against mammary tumors induced by DMBA, although for R-(+)equol there was a trend to delaying tumor formation. In summary, early exposure to equol was not chemopreventive, but neither did it increase tumor formation in response to DMBA, suggesting exposure in early life does not influence breast cancer risk.
Available from: Isabelle R Miousse
- "Several animal studies have shown that genistein given subcutaneously before puberty reduced the number and delayed the appearance of mammary tumors induced by DMBA (6, 17, 25, 40). Moreover, in contrast to adult exposure, prepubertal exposure to purified genistein and neonatal exposure to equol has also been associated with a reduction in the number of terminal end buds (TEBs, a marker of increased mammary gland differentiation ) (5,6,16,32,37). Therefore, consumption of isoflavones during early development when endogenous estrogens are low may actually increase differentiation in mammary tissues, which in turn may be responsible for the decrease in breast cancer risk associated with early soy consumption (47). Some animal studies have tested SPI rather than genistein. "
[Show abstract] [Hide abstract]
ABSTRACT: Isoflavones are phytochemical components of soy diets that bind weakly to estrogen receptors (ERs). To study potential estrogen-like actions of soy in the mammary gland during early development, we fed weanling male and female Sprague-Dawley rats a semi-purified diet with casein as the sole protein source from PND21 to PND33, the casein diet supplemented with estradiol (E2) at 10 μg/kg/day or the same diet substituting soy protein isolate (SPI) for casein. In contrast to E2, the SPI diet induced no significant change in mammary morphology. In males, there were 34 genes for which expression was changed ≥2-fold in the SPI group versus 509 changed significantly by E2, and 8 versus 174 genes in females. Nearly half of SPI-responsive genes in males were also E2-responsive, including adipogenic genes. Serum insulin was found to be decreased by the SPI diet in males. SPI and E2 both down-regulated the expression of ERα (Esr1) in males and females, and ERβ (Esr2) only in males. Chromatin immunoprecipitation (ChIP) revealed an increased binding of ERα to the promoter of the progesterone receptor (Pgr) and Esr1 in both SPI and E2 treated males compared to the casein group but differential recruitment of ERβ. ER promoter binding did not correlate with differences in Pgr mRNA expression. This suggests that SPI fails to recruit appropriate co-activators at E2-inducible genes. Our results are unsupportive of an E2-like proliferative effect of SPI feeding and indicate that SPI behaves like a SERM rather than a weak estrogen in the developing mammary gland.
[Show abstract] [Hide abstract]
ABSTRACT: The design of a radar altimeter, using synthetic aperture processing to achieve high spatial resolution in measurements of land topography, is described. The radar incorporates several novel features, such as digital generation of the transmit and deramp local oscillator waveforms, which allow very high processing gain to be achieved. Examples of experimental results obtained with the altimeter are also presented.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.