Dietary genistein stimulates mammary hyperplasia in gilts

Abstract

The possible role of the phytoestrogen genistein on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n 5 15), a control diet without soya (CTL0, n 5 15) or the CTLS diet supplemented with 2.3 g of genistein daily (GEN, n 5 15) from 90 days of age until slaughter (day 183 6 1). Both basal diets were isonitrogenous and isocaloric. Jugular blood samples were obtained on days 89 and 176 to determine concentrations of isoflavone metabolites (on day 176 only), prolactin, estradiol, progesterone, insulin-like growth factor 1 (IGF1), and N-telopeptide of type I collagen (NTx; on day 176 only). At slaughter, mammary glands were excised, parenchymal and extraparenchymal tissues were dissected, and composition of parenchymal tissue (protein, fat, dry matter (DM), DNA) was determined. Histochemical analyses of mammary parenchyma were performed. Dietary genistein increased parenchymal protein (P , 0.05) while decreasing DM (P , 0.05) and tending to lower fat content compared with the CTLS, but not the CTL0, diet. There was more parenchymal DNA (1.26 v. 0.92 mg/g, P , 0.05) in GEN than CTLS gilts, likely reflecting an increase in the quantity of mammary epithelial cells. Circulating concentrations of genistein were increased in GEN gilts (P , 0.001) but concentrations of hormones or NTx (indicator of bone collagen resorption) were not affected by GEN (P . 0.1). Percentage of estradiol receptor alpha (ERa)-positive epithelial cells was lower (P , 0.05) in GEN than CTLS gilts, whereas 5-bromo-2 0 -deoxyuridine labeling index was unaltered (P . 0.1). Transcript levels for ERa, ERb, IGF1, epidermal growth factor (EGF), epidermal growth factor receptor and transforming growth factor alpha were not altered by treatments. Supplementation of the diet with genistein during the growing phase in gilts, therefore, led to hyperplasia of mammary parenchymal tissue after puberty; yet, even though circulating genistein was increased, this was not accompanied by changes in mammary expression of selected genes or circulating hormone levels.

Effects of dose and route of administration of genistein on isoflavone concentrations in post-weaned and gestating sows

“…However, present results show that this is not likely to be the case as animals in the current study were also fed a soy-based diet. Nevertheless, current findings corroborate previous studies (Kuhn et al, 2004;Gu et al, 2006;Farmer et al, 2010) showing that genistein and daidzein are the two major isoflavones present in the circulation of swine.…”

“…The same was true for circulating concentrations of estradiol and IGF-I, which were not affected. This corroborates previous findings where dietary supplementation of 2.3 g of genistein to growing gilts for 93 days did not bring about any changes in circulating concentrations of the phytoestrogens daidzein, glycitein, or equol, or the hormones estradiol, IGF-I, prolactin or progesterone, when feeding a standard corn-soy diet (Farmer et al, 2010). Kuhn et al (2004) also saw no increase in IGF-I receptor mRNA expression in the longissimus dorsi of pigs fed various sources of soy products, which affected isoflavone concentrations.…”

“…This is in agreement with findings from Kuhn et al (2004) who noted that formation of equol is not a major route of phytoestrogen metabolism in pigs. On the other hand, one previous study showed equol to be produced in growing gilts fed a soy-based diet (Farmer et al, 2010) and this discrepancy was thought to be because of differences in the type of diet between studies. However, present results show that this is not likely to be the case as animals in the current study were also fed a soy-based diet.…”

“…Throughout the experiment, all sows were housed in individual stalls (0.6 3 2.1 m) and were fed 2.5 kg/day of a commercial gestation diet (14.2% CP, 13.1 MJ/kg DE, 0.6% lysine) at 0815 h. This diet contained 497 kg of corn, 175 kg of wheat shorts, 100 kg of wheat, 80 kg of soybean meal (48%), 60 kg of canola meal, 43 kg of ground oats and 45 kg of vitamin-mineral pre-mix per 1000 kg of diet. On the basis of soybean meal content, when extrapolating from a previous trial using similar diets (Farmer et al, 2010), the current diet should provide ,97, 100 and 10 mg/kg diet of genistein, daidzein and glycitein, respectively. Sows were weighed and their backfat thickness was measured ultrasonically at the last rib (Scanmatic SM-1, Medimatic, Hellerup, Denmark) on day 82 6 1 of gestation, following an overnight fast.…”

“…Genistein was recently shown to have beneficial effects -E-mail: Chantal.Farmer@agr.gc.ca in swine. Indeed, administration of genistein to gilts enhanced mammogenesis (Ford 2003;Farmer et al, 2010). Genistein can either be given per os or via injections, but there is no information in swine comparing the effects of the route of administration of genistein on circulating concentrations of isoflavones and hormones.…”