Within the mammalian olfactory sensory epithelium, experience-dependent changes in the rate of neuronal turnover can alter the relative abundance of neurons expressing specific chemoreceptors. Here we investigate how the mouse olfactory sensory receptor repertoire changes as a function of exposure to odors emitted from members of the opposite sex, which are highly complex and sexually dimorphic. Upon housing mice either sex-separated or sex-combined until six months of age, we find that sex-separated mice exhibit significantly more numerous differentially expressed genes within their olfactory epithelia. A subset of these chemoreceptors exhibit altered expression frequencies following both sex-separation and olfactory deprivation. We show that several of these receptors detect either male- or female-specific odors. We conclude that the distinct odor experiences of sex-separated male and female mice induce sex-specific differences in the abundance of neurons that detect sexually dimorphic odors.

Metabolic dysfunction underlies several chronic diseases. Dietary interventions can reverse metabolic declines and slow aging but remaining compliant is difficult. 17α-estradiol (17α-E2) treatment improves metabolic parameters and slows aging in male mice without inducing significant feminization. We recently reported that estrogen receptor α is required for the majority of 17α-E2-mediated benefits in male mice, but that 17α-E2 also attenuates fibrogenesis in liver, which is regulated by estrogen receptor β (ERβ)-expressing hepatic stellate cells (HSC). The current studies sought to determine if 17α-E2-mediated benefits on systemic and hepatic metabolism are ERβ-dependent. We found that 17α-E2 treatment reversed obesity and related systemic metabolic sequela in both male and female mice, but this was partially blocked in female, but not male, ERβKO mice. ERβ ablation in male mice attenuated 17α-E2-mediated benefits on hepatic stearoyl-coenyzme A desaturase 1 (SCD1) and transforming growth factor β1 (TGF-β1) production, which play critical roles in HSC activation and liver fibrosis. We also found that 17α-E2 treatment suppresses SCD1 production in cultured hepatocytes and hepatic stellate cells, indicating that 17α-E2 directly signals in both cell-types to suppress drivers of steatosis and fibrosis. We conclude that ERβ partially controls 17α-E2-mediated benefits on systemic metabolic regulation in female, but not male, mice, and that 17α-E2 likely signals through ERβ in HSCs to attenuate pro-fibrotic mechanisms.

A reconfigurable microfluidic building block platform for high throughput drug screening.

Metabolic dysfunction underlies several chronic diseases. Dietary interventions can reverse metabolic declines and slow aging but remaining compliant is difficult. 17α-estradiol (17α-E2) treatment improves metabolic parameters and slows aging in male mice without inducing significant feminization. We recently reported that estrogen receptor α is required for the majority of 17α-E2-mediated benefits in male mice, but that 17α-E2 also attenuates fibrogenesis in liver, which is regulated by estrogen receptor β (ERβ)-expressing hepatic stellate cells (HSC). The current studies sought to determine if 17α-E2-mediated benefits on systemic and hepatic metabolism are ERβ-dependent. We found that 17α-E2 treatment reversed obesity and related systemic metabolic sequela in both male and female mice, but this was partially blocked in female, but not male, ERβKO mice. ERβ ablation in male mice attenuated 17α-E2-mediated benefits on hepatic stearoyl-coenyzme A desaturase 1 (SCD1) and transforming growth factor β1 (TGF-β1) production, which play critical roles in HSC activation and liver fibrosis. We also found that 17α-E2 treatment suppresses SCD1 production in cultured hepatocytes and hepatic stellate cells, indicating that 17α-E2 directly signals in both cell-types to suppress drivers of steatosis and fibrosis. We conclude that ERβ partially controls 17α-E2-mediated benefits on systemic metabolic regulation in female, but not male, mice, and that 17α-E2 likely signals through ERβ in HSCs to attenuate pro-fibrotic mechanisms.