17β-estradiol can regulate the transcription of target genes by binding the classical nuclear receptor, estrogen receptor (ER) α or β to regulate behaviors but can also regulate behavior via non-classical means by regulating kinases or calcium flux via a putative receptor on the plasma membrane.  The physiological role of such non-genomic vs. genomic signaling, especially for behavior in rodents, is unclear.  We focus on behavioral outcomes regulated by non-classical estrogen signaling in inbred mice, by activation of a putative membrane ER called GPER-1/GPR30 or by using rapid time frames that preclude genomic action. 

Estrogen’s role in increasing aggressive behavior has usually been shown using gonadectomized mice, implanted with estrogens that are released chronically.  We have developed a novel paradigm where an aromatase inhibitor, letrozole, given in drinking water, greatly reduces both 17β-estradiol levels and subsequently aggressive behavior in male mice.  Administration of cyclodextrin conjugated 17β-estradiol can rapidly upregulate aggressive behavior in male within 20 minutes, suggesting that an activational effect via non-genomic signaling is sufficient to induce aggressive behavior. The receptors that may mediate this effect will be discussed.

In female mice, we have shown that the activation of a putative membrane receptor, the GPR30, increases lordosis behavior. We hypothesize that social behaviors may be modulated acutely by estrogens via the regulation of state anxiety. Hence, we have shown that GPR30 activation rapidly decreases anxiety in males but not in females and that this is correlated with the phosphorylation of the ERα.  Hence, in males as well as females, rapid signaling by estrogens can regulate social behaviors.

Supported by NSF CAREER IOS- IOS-1053716 and Tulane startup funds to N.V and LA Board of Regents to K.P.