Besides affecting the hypothalamus and other brain areas related to reproduction, ovarian
steroids have widespread effects throughout the brain, on serotonin pathways, catecholaminergic
neurons, and the basal forebrain cholinergic system as well as the hippocampal formation, a brain
region involved in spatial and declarative memory. Thus, ovarian steroids have measurable effects on
affective state as well as cognition, with implications for dementia. Two actions are discussed in this
review; both appear to involve a combination of genomic and nongenomic actions of ovarian
hormones. First, regulation of the serotonergic system appears to be linked to the presence of
estrogen- and progestin-sensitive neurons in the midbrain raphe as well as possibly nongenomic
actions in brain areas to which serotonin neurons project their axons. Second, ovarian hormones
regulate synapse turnover 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 (NMDA) receptors, whereas downregulation of these synapses involves
intracellular progestin receptors. A new, rapid method of radioimmunocytochemistry has made
possible the demonstration of synapse formation by labeling and quantifying the specific synaptic and
dendritic molecules involved. Although NMDA receptor activation is required for synapse formation,
inhibitory interneurons may play a pivotal role as they express nuclear estrogen receptor-alpha (ER).
It is also likely that estrogens may locally regulate events at the sites of synaptic contact in the
excitatory pyramidal neurons where the synapses form. Indeed, recent ultrastructural data reveal
extranuclear ER immunoreactivity within select dendritic spines on hippocampal principal cells,
axons, axon terminals, and glial processes. In particular, the presence of ER in dendrites is consistent
with a model for synapse formation in which filopodia from dendrites grow out to find new synaptic
contacts and estrogens regulate local, post-transcriptional events via second messenger systems.
Besides affecting the hypothalamus and other brain areas related to reproduction, ovariansteroids have widespread effects throughout the brain, on serotonin pathways, catecholaminergicneurons, and the basal forebrain cholinergic system as well as the hippocampal formation, a brainregion involved in spatial and declarative memory. Thus, ovarian steroids have measurable effects onaffective state as well as cognition, with implications for dementia. Two actions are discussed in thisreview; both appear to involve a combination of genomic and nongenomic actions of ovarianhormones. First, regulation of the serotonergic system appears to be linked to the presence ofestrogen- and progestin-sensitive neurons in the midbrain raphe as well as possibly nongenomicactions in brain areas to which serotonin neurons project their axons. Second, ovarian hormonesregulate synapse turnover in the CA1 region of the hippocampus during the 4- to 5-day estrous cycleof the female rat. Formation of new excitatory synapses is induced by estradiol and involvesN-methyl-D-aspartate (NMDA) receptors, whereas downregulation of these synapses involvesintracellular progestin receptors. A new, rapid method of radioimmunocytochemistry has madepossible the demonstration of synapse formation by labeling and quantifying the specific synaptic anddendritic molecules involved. Although NMDA receptor activation is required for synapse formation,inhibitory interneurons may play a pivotal role as they express nuclear estrogen receptor-alpha (ER).It is also likely that estrogens may locally regulate events at the sites of synaptic contact in theexcitatory pyramidal neurons where the synapses form. Indeed, recent ultrastructural data revealextranuclear ER immunoreactivity within select dendritic spines on hippocampal principal cells,axons, axon terminals, and glial processes. In particular, the presence of ER in dendrites is consistentwith a model for synapse formation in which filopodia from dendrites grow out to find new synapticcontacts and estrogens regulate local, post-transcriptional events via second messenger systems.
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Besides affecting the hypothalamus and other brain areas related to reproduction, ovarian
steroids have widespread effects throughout the brain, on serotonin pathways, catecholaminergic
neurons, and the basal forebrain cholinergic system as well as the hippocampal formation, a brain
region involved in spatial and declarative memory. Thus, ovarian steroids have measurable effects on
affective state as well as cognition, with implications for dementia. Two actions are discussed in this
review; both appear to involve a combination of genomic and nongenomic actions of ovarian
hormones. First, regulation of the serotonergic system appears to be linked to the presence of
estrogen- and progestin-sensitive neurons in the midbrain raphe as well as possibly nongenomic
actions in brain areas to which serotonin neurons project their axons. Second, ovarian hormones
regulate synapse turnover 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 (NMDA) receptors, whereas downregulation of these synapses involves
intracellular progestin receptors. A new, rapid method of radioimmunocytochemistry has made
possible the demonstration of synapse formation by labeling and quantifying the specific synaptic and
dendritic molecules involved. Although NMDA receptor activation is required for synapse formation,
inhibitory interneurons may play a pivotal role as they express nuclear estrogen receptor-alpha (ER).
It is also likely that estrogens may locally regulate events at the sites of synaptic contact in the
excitatory pyramidal neurons where the synapses form. Indeed, recent ultrastructural data reveal
extranuclear ER immunoreactivity within select dendritic spines on hippocampal principal cells,
axons, axon terminals, and glial processes. In particular, the presence of ER in dendrites is consistent
with a model for synapse formation in which filopodia from dendrites grow out to find new synaptic
contacts and estrogens regulate local, post-transcriptional events via second messenger systems.
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