115,117 Lesions of hypothalamic regions encompassing the DMH and the POA amplify HPA responses to stress.119,120 Furthermore, glutamate microstimulation of DMH neurons produces inhibitory postsynaptic potentials in hypophysiotropic neurons of the PVN,121 and stimulation of the POA attenuates the excitatory effects of medial amygdalar stimulation of glucocorticoid release.122 The POA is a potential site
of integration between gonadal steroids and the HPA axis. Accordingly, neurons Inhibitors,research,lifescience,medical of the POA are activated by gonadal steroids and express high levels of androgen, estrogen, and progesterone receptors.123,124 Hypothalamus: feeding centers Hypothalamic centers involved in the regulation of energy homeostasis directly innervate PVN neurons. Neurons in the Inhibitors,research,lifescience,medical arcuate nucleus are sensitive to circulating levels of glucose, insulin, and leptin These cells also synthesize neuropeptide Y (NPY), agouti-related peptide (AGRP), αmelanocyte stimulating hormone (αMSH), and exactly cocaineand amphetamine-regulated Inhibitors,research,lifescience,medical transcript (CART) which play critical roles in the regulation of feeding behaviors.125,127 In addition to their roles in energy homeostasis, arcuate neuropeptides have significant effects on HPA axis activity. Central injection of the orexigenic factor NPY results in
HPA axis activation128,129 and infusion of AGRP significantly increases CRF Inhibitors,research,lifescience,medical release from hypothalamic expiants.130 The anorectic peptides αMSH and CART have been reported to increase circulating levels of
ACTH and corticosterone,130,132 induce cAMP binding protein phosphorylation in CRF neurons,133 and stimulate CRF release from hypothalamic neurons.130,134 These studies suggest that the HPA axis is activated in Inhibitors,research,lifescience,medical response to positive and negative states of energy balance. The limbic system Limbic structures of the f orebrain contribute to the regulation of the HPA axis. Neuronal populations in the hippocampus, prefrontal cortex, and amygdala are the anatomical substrates for memory formation and emotional responses, and may serve as a link between the stress GSK-3 system and neuropsychiatrie disorders.86,135 The hippocampus, prefrontal cortex, and amygdala have significant effects on glucocorticoid release and behavioral responses to stress.84,136,137 However, these limbic structures have a limited number of direct connections with hypophysiotropic neurons of the PVN and are thought to regulate HPA axis activity through intermediary neurons in the BNST, hypothalamus, and brain stem.20,138,139 Limbic system: Z-VAD-FMK Caspase inhibitor hippocampus The hippocampus plays an important role in the terminating HPA axis responses to stress.84,139 Stimulation of hippocampal neurons decreases neuronal activity in the parvocellular division of the PVN and inhibits glucocorticoid secretion.