Ovine Corticotropin-Releasing Factor Administration in Normal Men

Abstract

We administered ovine corticotropin-releasing factor (CRF) as a bolus intravenous injection (1 µg/kg) at 09.00 and at 20.00 to assess the influence of circadian changes in the hypothalamic-pituitary-adrenal axis on the response to CRF. The increase in plasma ACTH levels after CRF was only slightly lower in the morning than in the evening. The plasma cortisol response to ACTH, however, was significantly greater in the evening than in the morning (p < 0.005). At both times of day CRF administration had no effect on plasma concentrations of GH, PRL, LH, AVP, insulin, PRA or glucose. No effects were observed on the hematopoietic system, kidneys or liver. In addition, CRF had no effect on heart rate, blood pressure or respiratory rate at the dose employed. Approximately 10% of the subjects complained of a transient upper body and facial hot flush. These observations indicate that the magnitude of the plasma cortisol rise after CRF depends on the time of administration.

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.

“…Note that this result is opposite of that for administration ofgraded boluses of exogenous CRF, where the greater release of ACTH and cortisol was found in the evening (17)(18)(19)(20). In those studies there was a negative correlation between basal cortisol levels and both ACTH and cortisol response to CRF stimulation (17)(18)(19)(20)40). In these previous studies the lesser response of ACTH to CRF in the morning was thought possibly to be due to feedback inhibition at the pituitary by the higher level of ambient cortisol levels in the morning.…”

“…In our study administration of synthetic vasopressin produced a markedly enhanced release of ACTH in the morning as compared with the evening, consistent with synergism of vasopressin with high endogenous CRF in the morning. Note that this result is opposite of that for administration ofgraded boluses of exogenous CRF, where the greater release of ACTH and cortisol was found in the evening (17)(18)(19)(20). In those studies there was a negative correlation between basal cortisol levels and both ACTH and cortisol response to CRF stimulation (17)(18)(19)(20)40).…”

“…The morning and evening responses ofACTH to administered vasopressin are the opposite of those to administered CRF (17)(18)(19)(20). The greatest ACTH response was not in the morning after vasopressin infusion, but in the evening after CRF infusion.…”

“…Although CRF has not been measured in portal vessels of man, it is hypothesized that the secretory bursts of ACTH result from pulses of CRF secreted into hypophyseal portal blood, with more frequent bursts of CRF occurring in the early morning (17). When CRF was administered to humans, the ACTH and cortisol response was reported to be lower in the morning than in the evening (18)(19)(20), but the mechanism of either the augmented sensitivity ofthe pituitary adrenal axis in the evening, or of the blunted sensitivity in the morning, is not known. Glucocorticoids have been shown to blunt or abolish CRF-induced ACTH release (21,22), and the lower morning response may simply be due to negative feedback.…”

Die Messung des freien Speichel-Cortisols vor und nach intravenöser Stimulation mit Corticotropin-Releasing Hormon. Der Einfluß basaler Cortisolspiegel auf die Stimulierbarkeit.

“…Insgesamt ist CRH jedoch gut verträglich (11). Es wurde daher von verschiedenen Autoren vorgeschlagen, die Substanz als Diagnostikum bei unterschiedlichen Störungen der Hypophysen-Nebennierenrinden-Achse zu benutzen (12,13,14,15). Sie hat in der Folge den mit erheblichen unangenehmen Nebenwirr kungen behafteten Lysin-Vasopressin-Test ersetzen können (16).…”