INHIBITION OF THE RESPONSE TO PITUITARY ADRENOCORTICOTROPHIC HORMONE IN THE HYPOPHYSECTOMIZED RAT BY CIRCULATORY CORTICOSTERONE

Abstract

SUMMARY The adrenal response to adrenocorticotrophin (ACTH), as determined by the secretion of corticosterone into adrenal vein blood,was measured in hypophysectomized rats in the presence of low and high levels of corticosterone in the peripheral circulation. To ensure that the level of corticosterone was low in the peripheral blood, the animals were hypophysectomized 24 hr. before the experiment, and one adrenal was removed before the start of infusion of ACTH. After the onset of the infusion the effluent from the remaining gland was collected in a receptacle, thus preventing any corticosterone produced under the influence of ACTH from reaching the general circulation. To study the effect of a high level of circulating corticosterone on the adrenal response to ACTH, corticosterone was injected subcutaneously, in beeswax and arachis oil, before the start of infusion of ACTH. In these experiments, too, the steroid secreted under the influence of ACTH was prevented from entering the general circulation. The peripheral levels attained by the injection of corticosterone were within the range observed during surgical stress, i.e. about 40 μg./100 ml. blood. When the corticosterone levels were within this range the response to a continuous infusion of ACTH was reduced by approximately 22% when compared with animals which had received no corticosterone and whose peripheral corticosterone levels were hardly measurable. These results suggest that corticosterone is probably involved in a direct feedback mechanism of adrenocortical secretion in the rat as its inhibitory effect on the response to ACTH can be demonstrated at peripheral levels of corticosterone which are within the range found during surgical stress.