Aromatization in Brain and Pituitary

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9605053 Callard While estrogen is generally regarded as a circulating steroid hormone derived from ovaries, testes, and placenta, it is well-established that this hormone is also produced in the brain, pituitary, and retina. Indeed estrogen is synthesized in these neural tissues from circulating gonadal androgen through a process referred to as aromatization. Estrogen production is controlled by an enzyme catalyst termed aromatase, which is the product of the CYP19 gene. Dr. Callard is interested in understanding how brain production of estrogen and consequent estrogen-dependent neural processes are controlled. Towards this aim, she has identified a model system in which aromatase and androgen receptors are extremely high in the brain. In examining the molecular mechanisms operating on CYP19 gene expression in this model, Dr. Callard recently found, for the first time, the presence of two functional CYP19 genes. One is expressed at high levels in brain and other neural tissues exclusively, and the second is expressed at much lower levels in both brain and ovary. Using innovative molecular technology, she will now characterize the molecular mechanisms unique to each of the two CYP19 genes. Since brain-formed estrogens have a critical role in neural development during fetal and newborn stages and have been implicated in the maintenance of brain function throughout life, Dr. Callard will use this information to examine who estrogen production is optimized for timing, location in different cell-types and neural circuits, and functional condition such as age, gender and hormonal status. This new knowledge will not only increase our understanding of the basic mechanism by which estrogen becomes available to act within brain cells but also places this process into a functional and evolutionary perspective.