Researchers from the University of Tsukuba have discovered that estrogen receptor (ER) β, expressed in the lateral septum of the limbic system, plays a key role in suppressing anxiety-like behavior exhibited by male mice in social situations. They also discovered that the distribution and expression domain of ERβ differs from that of ERα.
Estradiol (E2), a steroid sex hormone, plays an essential role in social behavior, including the regulation of social anxiety, which is anxiety experienced when meeting unfamiliar people. In men, testosterone secreted by the testes is converted to E2 in the brain, and E2 binds to two types of estrogen receptors (ERs), ERα and ERβ, to regulate social behavior. However, its neuroendocrine basis is not understood. In this study, the role of ERα and ERβ expressed in the lateral septum (LS), which modulates social anxiety, was investigated using male mice.
The researchers first investigated the expression of ERα and ERβ in LS using genetically modified male mice. ERβ-expressing cells in mice were labeled with red fluorescent protein, which revealed that the distributions of ERα and ERβ are different. In addition, the researchers investigated the effects of ERα or ERβ gene expression in the LS of male mice during social and nonsocial stress situations. The results show that social anxiety is increased by inhibiting ERβ expression. In addition, ERα- and ERβ-positive cells in the LS projected to different regions of the hypothalamus. Thus, the researchers concluded that ERα- and ERβ-expressing cells in the LS are distinct cell populations with different localizations and neuronal projections, and the ERβ population plays a critical role in the neural circuitry that regulates anxiety-like behavior in social situations.
This work was supported by Aid for Scientific Research grant 15H05724, 21K18547 and 22H02941 to SO.