Endocrinology, Vol 121, 1320-1328, Copyright © 1987 by Endocrine Society

ARTICLES

Diminished responsiveness of the hypothalamic-pituitary-adrenal axis of the rat during exposure to prolonged stress: a pituitary-mediated mechanism

C Rivier and W Vale
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.

Intact rats exposed to low or moderate intensity electroshocks for 3-5 h showed a marked increase in plasma ACTH levels 10 min after the beginning of the stress, followed by a decline despite continuous exposure to the stimulus. We have explored the role of steroid feedback, desensitization of the pituitary response to CRF, or changes in pituitary ACTH content in mediating this phenomenon. The following results were obtained. Exposure of adrenalectomized rats to shocks showed that removal of steroid feedback did not restore the ability of the animals to maintain elevated levels of circulating ACTH during electroshocks. To determine whether prolonged stress caused changes in pituitary sensitivity to CRF, intact rats received CRF, epinephrine, vasopressin, or phorbol ester at the end of the 3-h shock session; all secretagogues caused a significantly smaller increase in the plasma ACTH levels in intact rats subjected to low or moderate intensity shocks compared to that of control animals, which suggested that there was no specific desensitization to CRF. By contrast, pituitary responsiveness to CRF was not significantly altered in adrenalectomized rats submitted to low intensity shocks for 1-3 h; however, when moderate intensity shocks were used, adrenalectomized rats showed a blunting of the response to CRF comparable to that in intact animals. Finally, we observed a comparable decrease in the pituitary ACTH content of intact or adrenalectomized rats exposed to electroshocks; this decrease was proportional to the length and intensity of the shocks. We conclude that the inability of continuously stressed rats to maintain elevated plasma ACTH levels appears to be mediated through both the temporary decrease in a readily releasable pituitary ACTH pool and the negative feedback exerted by corticosterone.

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