Mechanisms Mediating Oestradiol Modulation of the Developing Brain

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The brain has been known to be a sensitive target organ for the permanent organisational effects of gonadal steroids for close to 50 years. Recent advances have revealed a variety of unexpected cellular mechanisms by which steroids impact on the synaptic profile of hypothalamic nuclei critical to the control of reproduction. This review focuses on three in particular: 1) prostaglandins in the masculinisation of the preoptic area and control of male sexual behaviour; 2) GABA in the arcuate nucleus and potential control of the anterior pituitary; and 3) non-genomic activation of phosphotydolinositol 3 (PI3) kinase and glutamate in the ventromedial nucleus, which is relevant to the control of female reproductive behaviour. The importance of cell-to-cell communication, be it between neurones or between neurones and astrocytes, is highlighted as an essential principle for expanding the impact of steroids beyond those cells that express nuclear receptors.

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