Sex Steroids and the Brain: Lessons from Animal Studies

Abstract

Gonadal steroid hormones have multiple effects throughout development on steroid responsive tissues in the brain. The belief that the cellular morphology of the adult brain cannot be modulated or that the synaptic connectivity is "hard-wired" is being rapidly refuted by abundant and growing evidence. Indeed, the brain is capable of undergoing many morphological changes throughout life and gonadal steroids play an important role in many of these processes. Gonadal steroids are implicated in the development of sexually dimorphic structures in the brain, in the control of physiological behaviors and functions and the brain's response to physiological or harmful substances. The effect of sex steroids on neuroprotection and neuroregeneration is an important and expanding area of investigation. Astroglia are targets for estrogen and testosterone and are apparently involved in the actions of sex steroids on the central nervous system. Sex hormones induce changes in the expression of glial fibrillary acidic protein, the growth of astrocytic processes and the extent to which neuronal membranes are covered by astroglial processes. These changes are linked to modifications in the number of synaptic inputs to neurons and suggest that astrocytes may participate in the genesis of gonadal steroid-induced sex differences in synaptic connectivity and synaptic plasticity in the adult brain. Astrocytes and tanycytes may also participate in the cellular effects of sex steroids by releasing neuroactive substances and by regulating the local accumulation of specific growth factors, such as insulin-like growth factor-I, that are involved in estrogen-induced synaptic plasticity and estrogen-mediated neuroendocrine control. Astroglia may also be involved in the regenerative and neuroprotective effects of sex steroids since astroglial activation after brain injury or after peripheral nerve axotomy is regulated by sex hormones.