Theoretical Consequences of Fluctuating Versus Constant Liganding of Oestrogen Receptor‐α in Neurones

A theory is put forward that emphasises differences in neuronal responses to fluctuations in steroid hormone levels compared to constant hormone levels. We propose that neuronal functions that regulate gonadotrophin release from the anterior pituitary tend to be more sensitive to rapid increases in the levels of oestrogens than they are to constant oestrogen levels. By contrast, neurones that control certain behavioral functions are affected just as well by constant oestrogen levels as by positively accelerating levels of oestrogen. In addition to providing examples of data from recent experiments that examine actions of the long‐term effects of oestrogen on mouse behaviour, we illustrate the behavioural effects of microinjections of adeno‐associated viral vectors of small interfering RNA directed against the mRNA for oestrogen receptor‐α (ERα). This manipulation provides for a long‐term loss of ERα function in a neuranatomically specific manner. The theoretical distinction between temporal features of oestrogen sensitivity of neuroendocrine versus behavioural function is not absolute, but is intended to stimulate new experimentation that examines temporal features of oestrogen administration.