Apoptosis during sexual differentiation of the bed nucleus of the stria terminalis in the rat brain.

The bed nucleus of the stria terminalis (BST) in the rat forebrain differs between males and females. To test whether apoptosis may contribute to the development of sex differences in the BST, the incidence of apoptosis was determined in sham-treated males and sham-treated females sacrificed on postnatal days (PN) 2, 4, 6, 8, 10, and 12 (PN 1 being day of birth). More apoptotic nuclei were found in the principal nucleus of the BST (BSTpr) in females than in males, whereas the reverse was true for the lateral division of the BST (BSTl). Moreover, the volume of the BSTpr was larger in males than in females, whereas there was no sex difference in the volume of the BSTl. Our results also confirmed earlier reports indicating that the incidence of apoptosis in the central part of the medial preoptic nucleus (MPNc) is higher in females than in males. No sex difference in apoptosis was found in the ventromedial hypothalamus (VMH) and paraventricular nucleus (PVN). The volume of the MPNc and VMH was larger in males than in females, whereas the PVN volume did not differ between males and females. To test whether sex differences in neonatal levels of gonadal steroids may cause sex differences in the incidence of apoptosis in the BSTpr, the incidence of apoptosis was compared between castrated males and females that were treated with testosterone propionate or vehicle on the day of birth. In the BSTpr of gonadal steroid-treated animals, the incidence of apoptosis was lower when compared to animals treated with vehicle, which was also true for the MPNc. These results are consistent with the hypothesis that gonadal steroids contribute to the sexually dimorphic differentiation of the BST by controlling the incidence of apoptosis.