scholarly journals Mammary Gland Morphology and Gene Expression Differ in Female Rats Treated with 17β-Estradiol or Fed Soy Protein Isolate

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 6021-6032 ◽  
Author(s):  
Martin J. J. Ronis ◽  
Kartik Shankar ◽  
Horacio Gomez-Acevedo ◽  
Leah Hennings ◽  
Rohit Singhal ◽  
...  
2008 ◽  
Vol 233 (11) ◽  
pp. 1348-1358 ◽  
Author(s):  
Jin-Ran Chen ◽  
Rohit Singhal ◽  
Oxana P. Lazarenko ◽  
Xiaoli Liu ◽  
William R. Hogue ◽  
...  

Beneficial effects of soy protein consumption on bone quality have been reported. The effects of other dietary protein sources such as whey protein hydrolysate (WPH) and rice protein isolate (RPI) on bone growth have been less well examined. The current study compared effects of feeding soy protein isolate (SPI), WPH and RPI for 14 d on tibial bone mineral density (BMD) and bone mineral content (BMC) in intact and ovariectomized (OVX) rapidly growing female rats relative to animals fed casein (CAS). The effects of estrogenic status on responses to SPI were also explored. Tibial peripheral quantitative computerized tomography (pQCT) showed all three protein sources had positive effects on either BMD or BMC relative to CAS ( P < 0.05), but SPI had greater effects in both intact and OVX female rats. SPI and E2 had positive effects on BMD and BMC in OVX rats ( P < 0.05). However, trabecular BMD was lower in a SPI + E2 group compared to a CAS + E2 group. In OVX rats, SPI increased serum bone formation markers, and serum from SPI-fed rats stimulated osteoblastogenesis in ex vivo. SPI also suppressed the bone resorption marker RatLaps ( P < 0.05). Both SPI and E2 increased alkaline phosphatase gene expression in bone, but only SPI decreased receptor activator of nuclear factor-κB ligand (RANKL) and estrogen receptor gene expression ( P < 0.05). These data suggest beneficial bone effects of a soy diet in rapidly growing animals and the potential for early soy consumption to increase peak bone mass.


2016 ◽  
Vol 297 ◽  
pp. 68-80 ◽  
Author(s):  
Martin J. Ronis ◽  
Horacio Gomez-Acevedo ◽  
Michael L. Blackburn ◽  
Mario A. Cleves ◽  
Rohit Singhal ◽  
...  

2009 ◽  
Vol 202 (1) ◽  
pp. 141-152 ◽  
Author(s):  
Rohit Singhal ◽  
Kartik Shankar ◽  
Thomas M Badger ◽  
Martin J Ronis

Although soy foods have been recognized as an excellent source of protein, there have been recent concerns regarding potential adverse effects of isoflavone phytochemicals found in soy products, which are known to bind and activate estrogen receptors. Here, we used global hepatic gene expression profiles in ovariectomized female Sprague–Dawley rats treated with 17β-estradiol (E2) or fed with soy protein isolate (SPI) as a means of estimating potential estrogenicity of SPI. Female Sprague–Dawley rats were fed AIN-93G diets containing casein (CAS) or SPI starting at postnatal day (PND) 30. Rats were ovariectomized on PND 50 and infused with E2 or vehicle in osmotic pumps for 14 d. Microarray analysis was performed on liver using Affymetrix GeneChip Rat 230 2.0. Serum E2 levels were within normal ranges for the rat and SPI feeding did not increase uterine wet weight in the absence or presence of E2. SPI feeding altered (P<0.05, ≥±1.5-fold) the expression of 82 genes, while E2 treatment altered 892 genes. Moreover, only 4% of E2-affected genes were also modulated by SPI, including some whose expression was reversed by SPI feeding. The interaction between E2 and SPI uniquely modulated the expression profile of 225 genes including the reduction of those involved in fatty acid biosynthesis or glucocorticoid signaling and an induction of those involved in cholesterol metabolism. The different hepatic gene signatures produced by SPI feeding compared with E2 and the lack of increase in uterine wet weight in rats fed with SPI suggest that SPI is not estrogenic in these tissues.


2013 ◽  
Vol 45 (22) ◽  
pp. 1072-1083 ◽  
Author(s):  
Isabelle R. Miousse ◽  
Neha Sharma ◽  
Michael Blackburn ◽  
Jamie Vantrease ◽  
Horacio Gomez-Acevedo ◽  
...  

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 semipurified diet with casein as the sole protein source from postnatal day 21 to 33, the same diet substituting soy protein isolate (SPI) for casein, or the casein diet supplemented with estradiol (E2) at 10 μg/kg/day. 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 vs. 509 changed significantly by E2, and 8 vs. 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 downregulated the expression of ERα ( Esr1) in males and females, and ERβ ( Esr2) only in males. Chromatin immunoprecipitation revealed an increased binding of ERα to the promoter of the progesterone receptor ( Pgr) and Esr1 in both SPI- and E2-treated males compared with 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 indicate that SPI behaves like a selective estrogen receptor modulator rather than a weak estrogen in the developing mammary gland.


2001 ◽  
Vol 20 (3) ◽  
pp. 165-174 ◽  
Author(s):  
Thomas M. Badger ◽  
Martin J. J. Ronis ◽  
Reza Hakkak

Dietary factors other than the traditional nutrients are found in the so-called functional foods. They are becoming increasingly recognized as potentially important for maintaining good health. Soybeans are rich in such factors thought to help prevent certain chronic diseases. Soy protein isolate (SPI) is one of the three major proteins used in infant formulas sold in the United States, with casein (CAS) and whey (WPH) proteins being the others. We have been studying the health effects of these proteins. Safety concerns have developed over the consumption of soy-based infant formula, partly because of the high circulating levels of the total isoflavones (phytoestrogens) during “critical periods of infant development.” There is a paucity of data on developmental, physiological, neurophysiological, behavioral, metabolic, or molecular effects of soy phytochemicals in humans, especially during pregnancy and infancy. We have studied the effects of CAS, SPI, and WPH in short-term, long-term, and multigenerational studies in rats. Aside from minor differences in body weight gain profiles, CAS-, SPI-or WPH-fed rats did not differ in development, organ weights, in vitro hepatic metabolism of testosterone (T), or reproductive performance. However, some endocrine-related functions differed between rats fed these proteins. We found that SPI accelerated puberty in female rats ( p <.05) and WPH delayed puberty in males and females, as compared with CAS ( p <.05). Gender differences were also found in gonadectomy-induced steroid responses. Male rats had normal serum T levels, but female rats fed SPI had reduced serum 17β-estradiol concentrations and a blunted 17β-estradiol response to ovariectomy, as compared to rats fed CAS or WHP ( p <.05). Female rats fed SPI or WHP or treated with genistein had reduced incidence of chemically induced mammary cancers ( p <.05) compared to CAS controls, with WHP reducing tumor incidence by as much as 50%, findings that replicate previous results from our laboratory. Together, these results suggest gender-specific differences in development and certain endocrine responses among rats fed diets composed of a single protein source such as those used in infant formulas. Whether similar developmental effects occur in human infants is unknown, but unlikely because (1) most infants do not consume such diets throughout life as these rats did, and (2) no such effects have been reported in millions of American infants fed infant formula containing these proteins. The long-term health consequence implications of early diet exposure to SPI and WPH, such as reduced breast cancer incidence, are likely to be very positive.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Martin Ronis ◽  
Isabelle Miousse ◽  
Horacio Gomez‐Acevedo ◽  
Leah Hennings ◽  
Kartik Shankar ◽  
...  

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