Vasopressin stimulation of adrenocorticotropin hormone (ACTH) in humans. In vivo bioassay of corticotropin-releasing factor (CRF) which provides evidence for CRF mediation of the diurnal rhythm of ACTH.

Abstract

The diurnal response of ACTH release to intravenously administered arginine vasopressin was tested in normal volunteers given consecutively moderate doses of vasopressin every 15 min (0.1, 03, 1.0, and 3.0 IU) at 2200 h and again at 0700 h (PM/AM). This protocol was repeated 4 wk later with the times reversed (AM/PM). A dose-related increase in ACIH secretion was observed in all subjects. When the AM response of the AM/PM protocol was compared with the PM response of the PM/AM protocol, the release of ACTH was greater in the morning (P < 0.05) as evaluated by the following criteria: peak value of ACTH (129.9±30.4 pg/ml in the AM vs. 57.1±20.2 in the PM), area under the curve (689 in the AM vs.259 in the PM); and, sensitivity of the ACTH dose-response curve (first significant increase in ACTH with 1 IU of vasopressin in the AM but not significant even after 3 IU in the PM). In addition, when the AM vasopressin testing followed a previous evening stimulation (PM/AM protocol), there was a blunted ACTH response compared with the AM/PM protocol.Corticotropin-releasing factor (CRF) is probably the major ACTH secretagogue, but since vasopressin acts synergistically with CRF to produce an augmented release of ACTH, we suggest that the ACTH response to administered vasopressin depends upon the ambient endogenous level of CRF. We interpret our data and published data that CRF produces a lesser release of ACTH in the AM as follows: in the morning endogenous CRF is high and administered CRF produces little further release of ACTH, but administered vasopressin acting synergistically with high endogenous CRF causes a greater release of ACTH; conversely, in the evening endogenous CRF is low and administered CRF causes a greater release of ACHI, but vasopressin (a weak secretagogue by itself) gives a low ACTH response. We conclude that vasopressin stimulation of ACTH secretion can be used as an in vivo bioassay of endogenous CRF, and that there is a diurnal rhythm of CRF in hypophyseal portal blood.

A Synergistic Adrenocorticotropin Response to Naloxone and Vasopressin in Normal Humans: Evidence That Naloxone Stimulates Endogenous Corticotropin-Releasing Hormone

“…Since there were no significant differences in the peak AVP concentrations achieved in these three tests, and the AVP-time curves were of similar configuration, the pitu itary stimulation resulting from AVP administration was comparable in all three tests. The development of abdomi nal symptoms in 3 of the subjects with AVP levels of this magnitude is also consistent with previous reports [42,43]; since these were not severe and occurred to a similar degree in all three tests in the affected volunteers, they are unlikely to have influenced the outcome of the study, par ticularly in view of the similar hemodynamic measure ments during the tests in which active AVP was given.…”

“…However, no published studies of CRH/AVP synergy em ploying exogenous AVP have measured plasma AVP con centrations. Dose-response studies of intravenous AVP administration to normal humans have demonstrated that while a peripheral plasma AVP concentration of 60 pmol/1 does not stimulate ACTH and cortisol release [42], levels of 135 pmol/1 cause a significant rise in both ACTH and cortisol [43]. Considerably lower AVP concentrations of 5-10 pmol/1, achieved by hypertonic saline infusion, will augment the stimulatory effect of synthetic CRH in vivo [6,7], and this is consistent with reports that very low intra venous doses of AVP or LVP, which do not by themselves significantly increase ACTH levels above basal, still sub stantially increase the ACTH response to human or ovine 203 CRH [41,[44][45][46].…”

Cerebrospinal Fluid Corticotropin-Releasing Factor (CRF) and Vasopressin Concentrations Predict Pituitary Response in the CRF Stimulation Test: A Multiple Regression Analysis

“…Second, CSF peptide concentrations were measured from samples obtained 24 h before the CRF stimulation test was performed. Although synchronizing both procedures at 4:00 pm on consecutive days eliminates potential confounding by circadian fluctuations in CRF secretion and HPA axis activity (Motomatsu et al, 1984;Watabe et al, 1987;Salata et al, 1988;Geracioti et al, 1992;Kling et al, 1994;Kellner et al, 1995;Keenan et al, 2001), it is not certain that CSF peptide concentrations are constant from one day to the next. Furthermore, the model produced in this study comprised of afternoon samples may not accurately depict neuroendocrine function at other times in the diurnal cycle.…”

“…Furthermore, the model produced in this study comprised of afternoon samples may not accurately depict neuroendocrine function at other times in the diurnal cycle. For example, a previous study comparing morning vs evening ACTH responses to AVP stimulation (Salata et al, 1988) suggests that a more pronounced positive correlation between CSF AVP concentrations and pituitary responses to CRF administration may have been observed if the clinical procedures had been conducted in the morning. Third, the study did not include an assessment of HPA axis counter-regulatory mechanisms.…”

True

“…5 In man, the same control occurs, as shown by responses to subthreshold vasopressin injections in the morning and at night; vasopressin stimulates ACTH secretion in the morning, during peak circadian activity when hypothalamic secretion of corticotropin-releasing factor (CRF) occurs, but does not at night, during the circadian trough. 13 Distinct cortisol controls of trough vs peak ACTH secretion can also be inferred from the results of studies of patients with partial adrenal enzyme de®ciencies. In these individuals, ACTH or 17-hydroxyprogesterone levels are extremely high during the peak of the rhythm, but are normal during the trough, provided that some cortisol secretion (from 2 to 5 mgadl) occurs.…”