Estrogen receptors in the human forebrain and the relation to neuropsychiatric disorders

The steroid hormone estrogen influences brain function and neuropsychiatric disorders, but neuroanatomical information about the estrogen receptors (ERs) are rather limited. The main focus of this article is to provide an overview of the current status of the ER distribution and possible function in the human brain. The ERs are ligand activated transcription factors that belong to the steroid hormone receptors, included in the nuclear receptor superfamily. To date, there are two known ER subtypes, alpha and beta. In the human forebrain, both estrogen receptor subtypes are predominantly expressed in limbic-related areas, although they show distinct distribution patterns. The ERalpha mRNA expression appears to dominate in the hypothalamus and amygdala, indicating that the alpha-subtype might modulate neuronal cell populations involved in autonomic and reproductive neuroendocrine functions as well as emotional interpretation and processing. In contrast, the hippocampal formation, entorhinal cortex, and thalamus appear to be ERbeta dominant areas, suggesting a putative role for ERbeta in cognition, non-emotional memory and motor functions. Clinical observations of estrogenic effects together with the information available today regarding ER expression in the primate brain provide important clues as to the functional aspects of the two ER subtypes. However, further characterization of the different phenotypes of the ER expressing cells in the human brain is needed as well as the delineation of the genes which are regulated by the ERs and how this transcriptional control correlates with human behavior and mental status.