Ovarian steroids have many effects on the brain throughout the lifespa
n, beginning during gestation and continuing into senescence. These ho
rmones affect areas of the brain that are not primarily involved in re
production, such as the basal forebrain, hippocampus, caudate putamen,
midbrain raphe, and brainstem locus coeruleus. Here we discuss three
effects of estrogens and progestins that are especially relevant to me
mory processes and identify hormonal alterations associated with aging
and neurodegenerative diseases. First, estrogens and progestins regul
ate synaptogenesis in the CA1 region of the hippocampus during the 4-
to 5-day estrous cycle of the female rat. Formation of new excitatory
synapses is induced by estradiol and involves N-methyl-D-aspartate (NM
DA) receptors, whereas synaptic downregulation involves intracellular
progestin receptors. Second, there are developmentally programmed sex
differences in the hippocampal structure that may help to explain why
male and female rats use different strategies to solve spatial navigat
ion problems. During the period of development when testosterone is el
evated in the male, aromatase and estrogen receptors are transiently e
xpressed in the hippocampus. Recent data on behavior and synapse induc
tion strongly suggest that. this pathway is involved in the masculiniz
ation or defeminization of hippocampal structure and function. Third,
ovarian steroids have effects throughout the brain, including effects
on brainstem and midbrain catecholaminergic neurons, midbrain serotone
rgic pathways, and the basal forebrain cholinergic system. Regulation
of the serotonergic system appears to be linked to the presence of est
rogen- and progestin-sensitive neurons in the midbrain raphe, whereas
the ovarian steroid influence on cholinergic function involves inducti
on of choline acetyltransferase and acetylcholinesterase according to
a sexually dimorphic pattern. Because of these widespread influences o
n these various neuronal systems, it is not surprising that ovarian st
eroids produce measurable cognitive effects after ovariectomy and duri
ng aging.