Comparative analysis of androgen and estrogen receptor mRNA expression in adult mouse hippocampus.

In hippocampus, androgens and estrogens influence neuronal plasticity via a range of nuclear or membrane-bound receptors. While much work has focused on determining their functions, a certain vagueness about the cellular expression of established receptors has remained. Moreover, novel candidates, such as the androgen-responsive zinc-transporter ZIP9, need to be inserted into the emerging picture. We used highly-sensitive RNAscope in situ hybridization and quantitative real-time PCR to examine the cellular and total hippocampal mRNA expression of androgen (AR, ZIP9) and estrogen receptors (ERα, ERβ, GPER1) in adult mouse hippocampus, considering sex and estrous cycle as variables. (1) Androgen receptors are more abundantly expressed than estrogen receptors. (2) AR and ZIP9 mRNA regularly co-localize in hippocampal neurons, but ZIP9 mRNA is more homogenously distributed and also expressed in astrocytes and microglia. (3) ERα and GPER1 are the predominant estrogen receptors (ERβ mRNA was very low), but exhibit differential expression patterns: GPER1 mRNA is preferentially expressed in glutamatergic neurons, while ERα is specifically expressed in a subpopulation of GABAergic interneurons. Both receptors were barely detectable in astrocytes and microglia. (4) ZIP9 mRNA expression varies during the estrous cycle, being significantly down-regulated if serum E2 is high, whereas ERα mRNA expression was generally higher in females. We provide a comprehensive cellular and quantitative expression analysis of androgen and estrogen receptors in adult mouse hippocampus, including for the first time mRNA expression data on ZIP9. Our data underline the necessity to consider sex and estrous cycle when studying sex hormone functions.