Sex- and hormone-dependent antigen immunoreactivity in developing rat hypothalamus

Morphological sex differences in adults can result from differential gonadal steroid exposure during critical perinatal periods. This study describes the use of a monoclonal antibody we have developed to study mechanisms of sexual differentiation of brain structure and function. Used as a marker in immunocytochemistry, antibody AB-2 revealed subsets of cells, including radial glia, transiently during the perinatal period. Peak reactivity in radial glia was on embryonic day 19 in males and on postnatal day 1 in females. On postnatal day 1, AB-2 immunoreactivity in radial glia was 2-fold greater in females than in males. Greater activity was detected in males on one side of the brain than the other (2- to 4-fold, depending on the region). To test the hormone dependence of this sex difference, pregnant rats were injected with testosterone propionate to expose fetal females to androgen on embryonic day 18. This resulted in lower levels of AB-2 immunoreactivity in radial glia of the treated female offspring on postnatal day 1 relative to control females, and the pattern was bilaterally asymmetric, approaching that of males. Thus the difference between sexes in immunoreactivity with AB-2 as a marker was hormone dependent in a predictable manner. Whether this marker is revealing a sex difference in accessibility of antigen by immunocytochemistry or a sex difference in intrinsic antigen levels is not yet resolved. In either case these results support the hypothesis that certain hormone-dependent molecular events occur transiently during development.