Estrogen’s actions in the brain

Abstract

When discussing estrogen’s activity in the CNS one has to consider that effects observed in in vitro cellular models and even more in in vivo models are the result of a mixture of actions. It is hard to separate receptor-mediated from receptor-independent activities completely. Various activities of estrogen that depend on or are independent from ERs are intertwined in a complex network of interactions. Nevertheless, there are certain estrogen effects that can be mainly ascribed to estrogen’s ability to bind and activate ERs. The receptor-dependency is frequently shown by using ER-antagonists or more recently by employing ERKO-models. But one has to realize that certain antagonists may also have opposing effects at the ER (see page 47/SERMs). Moreover, k.o.-mice, as just discussed, are also the results of many compensatory mechanisms. However, it is clear, whenever one manipulates an experimental system, the readout of the system itself is affected to some extent.