The Cerebral Cortex as a Target of Estrogen and the Neurotrophins

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9602029 Toran-Allerand The gonadal steroid, estrogen, has multiple effects on the brain. One of its well characterized actions is to regulate the activity of the reproductive axis. However, an additional action of perhaps even greater consequence, is to influence the growth and differentiation of neurons in the brain. Recently published studies by Dr. Toran-Allerand revealed that estrogens may be intimately involved in modulating growth factor production in the brain forming the basis for estrogen's growth modulating effects but ultimately, estrogen also alters cognitive function. Dr. Toran-Allerand is continuing to investigate the interplay between estrogen and growth factors by studying the signal transduction pathways elicited by receptor stimulation. In exciting preliminary results, evidence for receptor cross-talk has been found. These studies are continuing and have been enhanced by investigations to analyze key elements of the estrogen and growth factor systems, including receptor coupling and protein kinases. That estrogen interacts in neurons with growth factors and their receptors introduces an important new regulatory system with implications for the development of the neuronal targets of estrogen. Although sex differences in circulating estrogen and androgen levels during early life represent an important epigenetic influence and appear to play a crucial role, it remains to be determined precisely how exposure to circulating masculine and feminine gonadal steroid hormone levels are translated into permanent differentiation of the neural circuitry supporting sexually dimorphic behavioral patterns. By stimulating the synthesis of proteins required for neuronal differentiation, survival and maintenance of function, estrogen and growth factors, acting perhaps in concert, as well as reciprocally, may have important and intertwined developmental roles. Thus, mediation of estrogen action by interactions with locally synthesized growth factors an d their receptors may represent a universal mechanism by which the effects of hormones, such as estrogen, may exert local control and exhibit both tissue and developmental specificity's. These studies essentially provide the biological basis for gender differences in behavior among all animal species, including man.