Corncob bedding alters the effects of estrogens on aggressive behavior and reduces estrogen receptor-α expression in the brain

Abstract

There is growing appreciation that estrogen signaling pathways can be modulated by naturally occurring environmental compounds such as phytoestrogens and the more recently discovered xenoestrogens. Many researchers studying the effects of estrogens on brain function or behavior in animal models choose to use phytoestrogen-free food for this reason. Corncob bedding is commonly used in animal facilities across the United States and has been shown to inhibit estrogen-dependent reproductive behavior in rats. The mechanism for this effect was unclear, because the components of corncob bedding mediating this effect did not bind estrogen receptors. Here, we show in the California mouse (Peromyscus californicus) that estrogens decrease aggression when cardboard-based bedding is used but that this effect is absent when corncob bedding is used. California mice housed on corncob bedding also had fewer estrogen receptor-α-positive cells in the bed nucleus of the stria terminalis and ventromedial hypothalamus compared with mice housed on cardboard-based bedding. In addition, corncob bedding suppressed the expression of phosphorylated ERK in these brain regions as well as in the medial amygdala and medial preoptic area. Previous reports of the effects of corncob bedding on reproductive behavior are not widely appreciated. Our observations on the effects of corncob bedding on behavior and brain function should draw attention to the importance that cage bedding can exert on neuroendocrine research.

Fig. 1.

The effects of estrogens on aggression depend on cage bedding. Aromatase inhibition with fadrozole increased the number of bites (A) and decreased attack latency (B) on Carefresh bedding but not corncob bedding. *, P < 0.05; **, P < 0.01, planned comparison for effect of fadrozole; n = 10–14 per group.

Fig. 2.

Corncob bedding suppresses the number of ER-α-immunoreactive cells in the BNST and VMH but not the MEA or MPOA. **, P < 0.01, main effect of bedding; n = 7–11 per group.

Fig. 3.

Corncob bedding suppresses the number of pERK-immunoreactive cells. Fadrozole reduces the number of pERK-immunoreactive cells in the BNST and VMH but not the MEA or MPOA. **, P < 0.01; ***, P < 0.001, main effect of bedding; †, P < 0.01, planned comparison for effect of fadrozole; n = 7–11 per group.