The hippocampus is implicated in spatial and explicit memory functions (28) and is part of the limbic system and therefore a participant in the affective and vegetative states (29). It is a brain region that provides "context" and cognitive meaning to many appetitive and aversive events (30,31), and it is a major target for circulating adrenal steroids and or for their actions during stress and in the diurnal sleep-waking cycle (32). Sex differences have been described in hippocampal morphology involving the size of the dentate gyrus (33-35), and spatial learning with global spatial cues is faster in males than in females (7). This trait can be reduced in newborn male rats by castration, and it is enhanced in newborn female rats by neonatal treatment with estrogens (7); this may be the pathway for sexual differentiation, because the hippocampus transiently expresses estrogen receptors and aromatizing enzymes during the first 2 wk of neonatal life (36,37). Estrogen receptors are largely absent from the adult hippocampus, except for scattered interneuron-like cells in Ammon's horn (38,39) and some unidentified estrophilic cells in the entorhinal cortex. Yet there are some remarkable effects of estrogens on synaptogenesis (see below). Androgen receptors are expressed in the hippocampus of the male and female rat (40). The dentate gyrus is larger in males than in females, owing in part to sexual differentiation (33,41), and there is some preliminary evidence for sex differences in neurogenesis and granule cell death in adult voles captured in the wild (42).
Thyroid hormone treatment immediately after birth has specific effects on the basal forebrain, dentate gyrus, and CA3 region of the hippocampus that last into adult life. Transient neonatal hyperthyroidism enhances basal forebrain cholinergic markers and increases the size of the dentate gyrus and branching of dendrites of CA3 pyramidal neurons (35,43,44). There are sex differences, in that the developing male cholinergic system is much more enhanced by the neonatal hyperthyroid state (43). Moreover, the direction of the thyroid hormone effect in the hippocampal formation is very much like that of testosterone (T), namely, to increase the size of the dentate gyrus and increase innervation of the CA3 pyramidal neurons (33).
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