Neonatal estrogen blockade prevents normal callosal responsiveness to estradiol in adulthood

The rat corpus callosum (CC) is larger in males than females, and is respon sive to hormone manipulations during development. We previously demonstrate d that P25 ovariectomy (Ovx) enlarged (defeminized) adult CC, while P70 ova ry transfer (OvT) counteracted this enlarging effect, resulting in smaller (feminized) CC. Since OvT females were not Ovx'd until P25, they received s ome neonatal estrogen (E) exposure. Behavioral data suggest that adult resp onsiveness to ovarian hormones depends upon prior organization by neonatal E. It has not been determined whether a similar phenomenon occurs for the f eminization of brain morphology. The current experiment examined whether ou r previous finding of adult CC responsiveness to ovarian hormones depended upon neonatal E exposure. We investigated this by assessing the effects of P70 ovarian hormone replacement (via ovary transfer or E pellet) in females that received either (1) normal ovarian hormone exposure until P25 Ovx, or (2) the E receptor blocker tamoxifen from birth to P25 Ovx. Females receiv ing normal neonatal hormone exposure responded to P70 E in the female-typic al manner: E reduced CC size. In contrast, females receiving neonatal E blo ckade responded to adult E in the opposite manner: E increased CC size. As far as we are aware, this is the first report suggesting that neonatal E ex posure organizes the female brain so that it responds normally to the organ izing actions of E when later exposure occurs. These findings further chall enge the traditional model of female brain development, which asserts that normal female brain organization occurs by default, in the absence of gonad al hormone exposure. (C) 2000 Elsevier Science B.V. All rights reserved.