AVPV neurons containing estrogen receptor-beta in adult male rats are influenced by soy isoflavones

Lihong Bu,Edwin D Lephart

doi:10.1186/1471-2202-8-13

Abstract

BackgroundIsoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. It is known that 17beta-estradiol induces apoptosis in anteroventral periventricular nucleus (AVPV) in rat brain. Also, there is evidence that consumption of soy isoflavones reduces the volume of AVPV in male rats. Therefore, in this study, we examined the influence of dietary soy isoflavones on apoptosis in AVPV of 150 day-old male rats fed either a soy isoflavone-free diet (Phyto-free) or a soy isoflavone-rich diet (Phyto-600).ResultsThe occurrence of apoptosis in AVPV was examined by TUNEL staining. The incidence of apoptosis was about 10 times higher in the Phyto-600 group (33.1 ± 1.7%) than in the Phyto-free group (3.6 ± 1.0%). Furthermore, these apoptotic cells were identified as neurons by dual immunofluorescent staining of GFAP and NeuN as markers of astrocytes and neurons, respectively. Then the dopaminergic neurons in AVPV were detected by immunohistochemistry staining of tyrosine hydroxylase (TH). No significant difference in the number of TH neurons was observed between the diet treatment groups. When estrogen receptor (ER) alpha and beta were examined by immunohistochemistry, we observed a 22% reduction of ERbeta-positive cell numbers in AVPV with consumption of soy isoflavones, whereas no significant change in ERalpha-positive cell numbers was detected. Furthermore, almost all the apoptotic cells were ERbeta-immunoreactive (ir), but not ERalpha-ir. Last, subcutaneous injections of equol (a major isoflavone metabolite) that accounts for approximately 70–90% of the total circulating plasma isoflavone levels did not alter the volume of AVPV in adult male rats.ConclusionIn summary, these findings provide direct evidence that consumption of soy isoflavones, but not the exposure to equol, influences the loss of ERbeta-containing neurons in male AVPV.

Highlights

Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol
Consumption of soy isoflavones induces apoptosis in anteroventral periventricular nucleus (AVPV) The effects of dietary soy isoflavones on apoptosis in AVPV were examined by TUNEL staining on coronal brain sections, identified as a cell cluster at the rostral level of the third ventricle (Figure 1)
This study directly demonstrates that long-term exposure to dietary soy isoflavones induces neuronal apoptosis in the AVPV of adult male rats

Summary

Introduction

Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. There is evidence that consumption of soy isoflavones reduces the volume of AVPV in male rats. Phytoestrogens are naturally occurring, plant derived, non-steroid molecules that are structurally similar to 17beta-estradiol [1]. Dietary soy isoflavones exist as biologically active aglycones (daidzein and genistein) and biologically inactive glucosides (mainly daidzin and genistin). Daidzein can be further metabolized to equol, a potent and abundant molecule in rodents [2,3]. The structural similarity between isoflavones and 17beta-estradiol enables these molecules to exert moderate estrogenic or antiestrogenic properties via mammalian estrogen receptors (ER). Equol appears to bind ERbeta > ERalpha, in a similar manner to that of genistein [2,5]

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