Evidence for Multifactor Regulation of the Adrenocorticotropin Secretory Response to Hemodynamic Stimuli*

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Abstract
The contributions of corticotropin-releasing factor (CRF), arginine vasopressin (AVP), epinephrine and oxytocin to the ACTH secretory responses to hemorrhage were examined in rats. The relative significance of each of these putative ACTH regulatory factors is undefined with respect to net ACTH secretion. Initially, the effects of selective systemic pharmacological blockade of individual factors on the ACTH response were examined. Immunoneutralization of CRF reduced resting ACTH levels below the detection limits of a radioimmunoassay and abolished treatment with a potent AVP antagonist reduced the ACTH secretory response by 55% and 38%, respectively. Further evidence for multifactor regulation of hemodynamically evoked alterations in ACTH secretion was obtained by measurement of the concentration of these factors in the hypophysial portal circulation during hemorrhage. Immunoreactive CRF, AVP, oxytocin and epinephrine were present in the portal plasma at concentrations within a range shown to evoke ACTH secretion from cultured pituitary cells when presented alone or in combination. The concentration of all of these were significantly elevated during hemorrhage. During atrial pulsation, a stimulus mimicking volume loading and associated with a reduction of systemic ACTH levels, significant decline in portal concentrations of immunoreactive AVP coupled with a nonsignficant trend toward reduced portal immunoreactive CRF levels was observed. Multifactor regulatory control of ACTH secretion in response to hemodynamic stimuli was suggested.