Medial preoptic estrogen receptor-beta blunts the estrogen receptor-alpha mediated increases in wheel-running behavior of female rats

Estrogens are believed to enhance rodent voluntary wheel-running through medial preoptic (mPOA) estrogen receptor α (ERα) signaling, with little role attributed to estrogen receptor β (ERβ). Systemic ERβ activation has been shown to mitigate ERα driven increases in wheel-running. Therefore, the present goal was to determine whether ERβ signaling in the mPOA plays a similar modulatory role over ERα. We utilized outbred wild-type (WT) and rats selectively bred for low voluntary running (LVR) behavior to address whether mPOA ERβ signaling blunts ERα driven wheel-running behavior and immediate-early gene (Fos, Zif268, and Homer1) mRNA induction. Further, we addressed baseline mPOA mRNA expressions and circulating 17β-estradiol levels between female WT and LVR rats. Following ovariectomy, WT rats reduced running behavior ∼40 %, with no effect in LVR rats. Intra-medial preoptic injection of the ERα-agonist propylpyrazoletriol (PPT) increased wheel-running ∼3.5-fold in WT rats, while injections of the ERβ-agonist diarylpropionitrile (DPN) or a combination of the two agonists had no effect. Similarly, ERα-agonism (PPT) increased Fos and Homer1 induction ∼3-fold in WT and LVR isolated mPOA neurons, with no effect of the ERβ-agonist DPN alone or in combination with PPT, suggesting medial-preoptic ERβ activity may blunt ERα signaling. LVR rats exhibited higher mPOA mRNA expressions of Esr1, Esr2 and Cyp19a1, lower normalized uterine wet weights and lower 17β-estradiol plasma levels compared to WT, suggesting their low running may be due to low circulating estrogen levels. Collectively, these findings highlight mPOA ERβ as a potential neuro-molecular modulator of the estrogenic control of wheel-running behavior.