Abstract
17β-Estradiol (E2) regulates the expression of female sexual behavior by acting through estrogen receptor (ER) α and β. Previously, we have shown that ERβ knockout female mice maintain high level of lordosis expression on the day after behavioral estrus when wild-type mice show a clear decline of the behavior, suggesting ERβ may be involved in inhibitory regulation of lordosis. However, it is not identified yet in which brain region(s) ERβ may mediate an inhibitory action of E2. In this study, we have focused on the dorsal raphe nucleus (DRN) that expresses ERβ in higher density than ERα. We site specifically knocked down ERβ in the DRN in ovariectomized mice with virally mediated RNA interference method. All mice were tested weekly for a total of 3 weeks for their lordosis expression against a stud male in two consecutive days: day 1 with the hormonal condition mimicking the day of behavioral estrus, and day 2 under the hormonal condition mimicking the day after behavioral estrus. We found that the level of lordosis expression in ERβ knockdown (βERKD) mice was not different from that of control mice on day 1. However, βERKD mice continuously showed elevated levels of lordosis behavior on day 2 tests, whereas control mice showed a clear decline of the behavior on day 2. These results suggest that the expression of ERβ in the DRN may be involved in the inhibitory regulation of sexual behavior on the day after behavioral estrus in cycling female mice.
Highlights
The expression of female sexual behavior undergoes cyclic change during an estrus cycle
Except the day of behavioral estrus and the day after, βERKO females express very little receptive behavior similar to WT females [4]. To replicate this finding in more hormonally controlled setting, we performed a preliminary experiment in ovariectomized βERKO females treated with exogenous ovarian steroids. We found that these females continuously showed elevated levels of lordosis expression 72 h after estradiol benzoate (EB) and 24 h after progesterone administration that mimic typical hormonal condition of the day after behavioral estrus
In addition to these mice in which associated virus (AAV)-shERβ was successfully infused into the entire dorsal raphe nucleus (DRN), there were five females in which AAV-shERβ was not spread in the mediodorsal area of dorsal part of the nucleus (Figure 4)
Summary
The expression of female sexual behavior undergoes cyclic change during an estrus cycle. 17β-estradiol (E2) plays an essential role in this cyclic regulation of the behavior. Lordosis, a stereotypical female sexual behavior is expressed at high levels only during the time around ovulation, the period called as “behavioral estrus” occurring subsequently to the exponential elevation of circulating E2. E2 is known to act through at least two receptor subtypes, estrogen receptor (ER) α and β. Studies using knockout mouse models have shown that the level of sexual behavioral expression is greatly reduced in ERα knockout (αERKO) females [1,2,3] whereas in the ERβ knockouts (βERKO), such alteration is not observed [4, 5]. It has been reported that the selective ERα
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