Estrogen Increases Locomotor Activity in Mice through Estrogen Receptor alpha: Specificity for the Type of Activity

SONOKO OGAWA, JOHNNY CHAN, JAN-ÅKE GUSTAFSSON, KENNETH S. KORACH, AND DONALD W. PFAFF

Endocrinology 2002

                Past literature has demonstrated that estrogen can regulate running wheel activity in both female and male rats and from a previously blogged paper it was shown that this running activity is highest in estrous stages where plasma estrogen is elevated. Studies have also shown that the medial preoptic area is one of the brain sites responsible for the effects of estrogen. There are two different nuclear types of estrogen receptors: alpha and beta. These are both shown to be localized to the medial preoptic area. The purpose of this study was the assess the effect that estrogen would have on mice that were lacking either the alpha or beta receptor.

                172 mice were used, both male and female. Mice were either lacking the gene for estrogen receptor alpha or beta or were wile type mice. They were kept on 12:12 light dark cycle and group housed. At 9-11 weeks mice were gonadectomized and separated into groups. Groups consisted of estrogen receptor beta and alpha knock outs and their respective wild types in both males and females. Each of these groups either received placebo or 16 ng/d or 160 ng/d replacement of estrogen benzoate. Mice were given one week to recover from surgery and implanted with the treatment or placebo and then given another week before they were given access to a running wheel. At this point the mice were housed individually and the revolutions of the wheel per day was recorded.

                Results of the study show that in both wild type female groups there was significantly increased running activity in the estrogen treated groups as compared to the placebo. Significant difference was only seen in the high dose in the alpha wild type group but was seen in both doses in the beta wild type group. In the alpha knock out group this effect of estrogen was not seen and there was no difference between treatment and placebo. In the beta knock out group both doses of the treatment increased running compared to placebo. The effect of estrogen treatment was lower in the beta knock out than in the beta wild type. In males, treatment increased running activity in both wild types and this was abolished in alpha knockout. Estrogen increased running activity in the beta knock out similar to the beta wild type.

                These results indicate that it is indeed primarily the estrogen receptor alpha that is responsible for modulating the running wheel activity. This is consistent with past research with this group that showed that activation of estrogen receptor beta did not increase running. The results from this study also indicate that it may be that ER beta also plays a role as the effect of estrogen was less in the beta knock out than the beta wild type. This was an interesting paper that tried to identify the mechanism that estrogen has in affecting the running wheel activity of rodents. It is interesting that they used knock out mice that were obtained from a supplier calling into question the effect that knocking these genes out early in the rats life had on its overall development.