In the rat the sexual differentiation of the brain is highly dependent upon the presence of estrogen and estrogen receptors during a critical period of brain sexual differentiation. The estrogen is produced intracellulary through the conversion of testosterone from the fetal testes into estrogen - a process referred to as aromatization. This conversion is under the control of an enzyme, or complex of enzymes, called aromatase. Recently, the PI in colloboration with Drs. Charles Roselli and John Resko have demonstrated in the testicular feminized male rat that this enzyme in some, but not all, brain areas is dependent upon the presence of an androgen receptor. On the basis of these studies, we have inferred that the same process may be operating during the critical period of brain sexual differentiation. Thus the latter process would ultimately depend upon the presence of androgen receptors at this time in addition to the need for estrogen and estrogen receptors. The intent of this proposal is, therefore, to explore the possibility that androgen receptor- dependent aromatization (ARDA) does occur during the perinatal critical period of development and to study the long-term behavioral and neuroendocrine consequences of interferring with the androgen receptor at this time. Since the regulation of the aromatase enzyme complex is clinically important in brain sexual differentiation and is some types of breast tumors, this work will provide further insite into the regulation of this enzyme and into developmental processes that are unique to the brain.
