Steroid hormone action in the brain: cross-talk between signalling pathways

Ovarian steroid hormones, oestradiol and progesterone, modulate neuroendocrine functions in the central nervous system, resulting in alterations in physiology and behaviour. The classical model of steroid hormone action assumes that these neural effects are predominantly mediated via their intracellular receptors functioning as 'ligand-dependent' transcription factors in the steroid-sensitive neurones regulating genes and genomic networks with profound behavioural consequences. Studies from our laboratory demonstrate that, in addition to their cognate ligands, intracellular steroid receptors can be activated in a 'ligand-independent' manner by the neurotransmitter dopamine, which alters the dynamic equilibrium between neuronal phosphatases and kinases. A high degree of cross-talk between membrane-initiated signalling pathways and the classical intracellular signalling pathways mediates hormone-dependent behaviour in mammals. The molecular mechanisms, by which a multitude of signals converge with steroid receptors to delineate a genomic level of cross-talk in brain and behaviour are discussed.