Steroid hormones profoundly influence the structure and function of the central nervous system during development and throughout the vertebrates' lifespan. While the major source of testosterone and estradiol comes from the gonads, the brain also produces steroids. Aromatase enzymes responsible for the metabolism of androgen into estrogen are localized within specific target neurons in discrete brain regions, such as the hypothalamus. In some species of vertebrates, aromatase is not found in testes or adrenals. Dr. Schlinger will determine whether the major source of circulating estrogen in these males is derived from aromatization of androgens in the brain. This has important theoretical ramifications because the brain may not only be a target of steroid hormones but also a major source of a circulating steroid. He will also examine the role of brain estrogen synthesis in the regulations of sex differences in brain development and function. To accomplish these goals, Dr. Schlinger will measure the amount of estrogen recovered in discrete brain regions, non-neural tissues and the vascular system following injection of androgen. He will then identify the source of the androgen substrate for the brain to produce estrogen. Finally, Dr. Schlinger will quantify the activity of aromatase enzymes and define their subcellular localization within neurons of the hypothalamus. These studies will lead to new insights in the mechanisms underlying hormone-brain interactions. Increasing our knowledge about the basic processes underlying normal neuroendocrine events will contribute towards to a better understanding of birth defects that result from insufficient and/or excessive exposure to a particular steroid hormone.
