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This paper summarizes recent work from this laboratory concerning the interaction of radioactive testosterone and various estrogens with brains of newborn rats. Testosterone7-3H is shown to be converted in vivo to estradi Ol7-3Hand this product is retained by cell nuclei in hypothalamus and limbic structures to a degree which points to the existence of putative estrogen receptor sites in the neonatal brain. This inference has been verified by in vivo studies using 3H-estradiol, 3H-diethylstilbastrol (DES) and 3H-II(3-methoxy I7 oc-ethynyl 17 (3-estradiol (RU 285) Cell nuclear retention of radioactive estrogens is prevented by non-radioactive 17(3-estradiol and i7a-estradiol and by the non-steroidal anti-estrogen CI6 28, and is not significantly reduced by a variety of non-radioactive 5a-reduced androgens or by progesterone. Cell nuclear labeling is substantial in hypothalamus, amygdala, preoptic area, and much lower in cerebellum and midbrain and brainstem. Cerebral cortex is noteworthy because it lacks significant aromatization capability and yet retains 3H-estrogens in a manner similar in specificity and intensity of labeling to hypothalamus, amygdala and preoptic area. The developmental changes of estrogen binding capacity are described. The neonatal brain and blood also contains another estrogen binding protein (fEBP-fetoneonatal estrogen binding protein) which binds 3H-estradiol but to a far lesser extent binds synthetic estrogens like 3H-DES and 3H-RU 285. The ability of 3H-estrogens to bind in vivo to cell nuclear receptor sites appears to be inversely related to their binding to fEBP. Hence, the protective role for this fEBP against potentially deleterious effects of estradiol17 Pis strongly supported, and the potential dangers of certain synthetic estrogens are once again demonstrated. The relationship of these results to the process of sexual differentiation is discussed.

INTERACTIONS OF TESTOSTERONE AND ESTRADIOL WITH THE NEONATAL RAT BRAIN : PROTECTIVE MECHANISM AND POSSIBLE RELATIONSHIP TO SEXUAL DIFFERENTIATION