THE ONTOGENY OF ESTROGEN-RECEPTORS IN HETEROCHRONIC HIPPOCAMPAL AND NEOCORTICAL TRANSPLANTS DEMONSTRATES AN INTRINSIC DEVELOPMENTAL PROGRAM

We investigated the intrinsic vs. environmental regulation of estrogen receptor (ER) ontogeny in the neocortex, hippocampus and hypothalamus by employing a heterochronic transplantation paradigm. These studies were based on previous reports demonstrating that neural ER develop as ynchronously with quantitatively distinct ontogenetic profiles in vari ous brain regions. Fetal (E14-15) hippocampal, frontal cortical or hyp othalamic preoptic area (HPOA) primordial tissue was grafted into fron tal cortical lesion cavities made in newborn (PND-0) rats. Thus, the g rafted tissue was 1 week younger than the host. Two and 4 weeks follow ing transplantation surgery, which corresponds to a theoretical donor age of PND-7 and PND-21, the grafts, a region of the host neocortex su rrounding the transplant, and the host hippocampus, frontal cortex or HPOA (depending on graft type) were assayed for ER content using in vi tro binding assays. ER concentration in hippocampal grafts at theoreti cal age PND-7 were significantly higher than those found in the host ( PND-14) hippocampus and in the host neocortex adjacent to the transpla nt. By theoretical graft age PND-21, ER concentration in hippocampal t ransplants had decreased to levels comparable to those found in the ho st. This developmental pattern is analogous to that previously reporte d for the in situ hippocampus. A similar profile of ER concentration c orresponding to the donor age developmental timetable was observed in neocortical grafts. ER levels in HPOA grafts did not change from theor etical donor age PND-7 to PND-21, which also corresponds to the normal ontogenetic profile. These data suggest that region-specific developm ental patterns of ER expression in the rat brain are specified by embr yonic day 14.