THE SITE OF THE BLOCKING ACTION OF DEXAMETHASONE ON STRESS-INDUCED PITUITARY ACTH RELEASE

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Abstract
SUMMARY: Male white rats were injected subcutaneously with graded doses of dexamethasone acetate 16 hr. before exposure to noxious stimuli. The rate of corticosteroid production by adrenal glands in vitro served as an index of ACTH release. The corticotrophic effect of environmental changes was readily suppressed by pretreatment with 50 μg. of dexamethasone, 125 μg. blocked the effect of histamine phosphate, 250 μg. the effect of noise and at least 500 μg. were needed to suppress the effect of unilateral adrenalectomy. The adrenal response to ACTH was not affected by pretreatment with dexamethasone. The effect of lysine vasopressin on ACTH release diminished with increasing amounts of dexamethasone; a complete block was obtained with 500 μg. In rats bearing extensive lesions in the median eminence pretreatment with dexamethasone also suppressed the corticotrophic effect of lysine vasopressin and of hypothalamic extracts. Dexamethasone pretreatment did not significantly alter the ACTH content of the pituitary of intact, shamoperated or lesioned rats. It is concluded that the blocking action of dexamethasone is located in the anterior pituitary.