GPR30/GPER-1 mediates rapid decreases in TLR4 expression on murine macrophages.

Studies to define the effects of estrogens on immune function have yielded conflicting results. The recent demonstration that GPR30 can mediate rapid non-genomic events and may function as a novel transmembrane estrogen receptor could provide a mechanism underlying such findings. In this study, we have investigated the ability of GPR30 to regulate cell-surface expression of Toll-like receptor 4 (TLR4), a key molecule in the perception of bacterial lipopolysaccharide (LPS) by immune cells.

Estrogens augment cell surface TLR4 expression on murine macrophages and regulate sepsis susceptibility in vivo.

Gender-based differences exist in infectious disease susceptibility. In general, females generate more robust and potentially protective humoral and cell-mediated immune responses after antigenic challenge than their male counterparts. Furthermore, evidence is accumulating that sex may also influence the early perception of microbial challenges and the generation of inflammatory immune responses such as sepsis.

Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity.

Though gender-based differences in the development of protective or pathological adaptive host responses have been widely noted, it is becoming apparent that sex may also influence the early perception of microbial challenges and the generation of inflammatory immune responses. These differences may be due to the actions of reproductive hormones, and such a hypothesis is supported by the presence of receptors for these hormones in a variety of immune cell types. Androgens such as testosterone have been shown to decrease immune functions, including cytokine production.