MECHANISMS OF NEUROENDOCRINE REGULATION

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Investigation has focused on the mechanism of regulation of the hypothalamic and pituitary function during stress. Immunohistochemical studies revealed that while acute stress causes marked release of corticotropin releasing hormones (CRH) and vasopressin (VP), chronic stress is accompanied by increases in vasopressin in te parvicellular system. To determine the role of VP on the changes in pituitary responsiveness observed during chronic stress, the function of the hypothalamic-pituitary-adrenal axis was studied during chronic osmotic stimulation, a potent stimulus of VP secretion. Water deprivation for 48 hr caused marked increases in plasma VP, VP mRNA and immunoreactive VP in magnocellular neurones. In spite of the increases in VP, pituitary ACTH responses to CRH injection or acute stress were reduced, in intact as well as in adrenalectomized rats, indicating that the reduced ACTH responses were not due to glucocorticoid feedback. These studies show that the parvicellular, but not the magnocellular VP system plays a role in the control of ACTH secretion during chronic stress. Studies on the relationship between CRH receptor regulation and corticotroph function showed no correlation between changes in CRH receptor and POMC mRNA levels or peptide release in anterior or intermediate pituitary of chronically stressed rats. This indicates that stress-induced changes in pituitary responsiveness are not due to changes in pituitary CRH receptors. The hypersensitivity of the ACTH responses to a novel stimulus, despite sustained increases in plasma corticosterone, suggest an alteration of the glucocorticoid feedback mechanism during chronic stress. Measurement of glucocorticoid receptors showed differential changes in receptor concentration following chronic stress, with decreases in the pituitary and hippocampus and increases in the PVN, and NTS. Chronically stressed adrenalectomized rats receiving corticosterone replacement, showed no changes in glucocorticoid receptors, but hypersensitivity of the ACTH response to a novel stress indicating that glucocorticoid receptor changes are not responsible for the altered feedback.