ABSTRACT
The brain is one of the specific target tissues for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in brain areas of the central nervous system (CNS), through the binding with specific receptors. The action of sex hormones is not limited to the regulation of endocrine functions and mating behavior: the identification of estrogen, progestin and androgen receptors outside the classical CNS regions, such as pituitary and hypothalamus, justifies their role in controling different brain functions. In particular, specific receptors for gonadal steroids have been localized in the amygdala, hippocampus, cortex basal forebrain, cerebellum locus coeruleus midbrain rafe nuclei, glial cells and central gray matter, confirming an involvement of sex hormones in controling wellbeing, cognitive functions and memory processes in physiological as well as in pathological conditions.1−3
The mechanism of action of these steroids in the CNS is similar to that observed in the peripheral target organs, producing both genomic and nongenomic effects. In the genomic mechanism, steroids induce relatively long-term actions on neurons by activating specific intracellular estrogen receptors (ERα and ERβ) that modulate gene transcription and protein synthesis. Thus, gonadal steroids modulate the synthesis, release and metabolism of many neuropeptides and neuroactive transmitters, and the expression of their receptors.4 ERα and ERβ are differently expressed throughout the rat brain and there is anatomical evidence of distinct roles of each subtype. Hybridization histochemical studies have shown that both receptors are present in the rat cortex, pituitary and hypothalamus (ERα mostly in the arcuate and ventromedial nuclei, while ERβ is mostly present in the paraventricular and ventromedial nuclei), while the cerebellum expresses only ERα and the hippocampus expresses particulary ERβ.5
