Evidence for multifactor regulation of the adrenocorticotropin secretory response to hemodynamic stimuli.

We have examined the contributions of corticotropin-releasing factor (CRF), arginine vasopressin (AVP), epinephrine, and oxytocin to the ACTH secretory responses to hemorrhage. 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 our RIA and abolished the secretory response to hemorrhage. Ganglionic blockade or 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 concentrations 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 concentrations 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, we observed a significant decline in portal concentrations of immunoreactive AVP coupled with a nonsignificant trend toward reduced portal immunoreactive CRF levels. These observations are highly suggestive of multifactor regulatory control of ACTH secretion in response to hemodynamic stimuli.