Diurnal Variation in the Response of Plasma Adrenocorticotropin and Cortisol to Intravenous Ovine Corticotropin-Releasing Hormone*

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Abstract
To determine whether the plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol responses to ovine corticotropin-releasing hormone (oCRH) depend on the time of day, we administered 1 μg/kg BW synthetic oCRH as an iv bolus dose to five normal men at their usual time of awakening between 0530–0740 h, at 1600 h, and at 2300 h. Mean basal plasma IR-ACTH and IR-cortisol levels were highest upon awakening, intermediate at 1600 h, and lowest at 2300 h, reflecting the diurnal rhythm of ACTH secretion. There was no significant difference in the plasma IR-ACTH response to oCRH at different times of the day. In contrast, the mean maximum plasma IR-cortisol increment and mean integrated response were 2-and 2.6-fold greater (P < 0.05), respectively, at 2300 h than upon awakening. In another study, oCRH was given in the morn, lg (0700–0900 h) to 22 normal men and in the late afternoon (1600–1800 h) to 24 normal men. Mean basal plasma IR-ACTH and IRcortisol levels were significantly higher (P < 0.001) in the morning [24 ± 3 pg/ml (mean ± SEM) and 10.6 ±0.8 Mg/dl, respectively] than in the afternoon (13 ± 2 pg/ml and 5.6 ± 0.6 Mg/dl, respectively). Mean peak plasma IR-ACTH was slightly greater in the morning (60 ± 5.5 pg/ml) than in the afternoon (47 ± 5.5 pg/ml), the mean maximum plasma IR-ACTH increments were the same (35 ± 4 and 34 ± 5 pg/ml, respectively), and the mean integrated IR-ACTH response was slightly less in the morning (2036 ± 414 us. 2365 ± 358 pgmin/ml), but none of these differences was statistically significant. Mean peak plasma IR-cortisol concentrations in the morning and afternoon were similar (18.7 ± 0.7 and 17.3 ± 0.9 Mg/dl, respectively), but the mean maximum plasma IR-cortisol increments (8.1 ± 0.8 and 11.7 ± 0.9 /ig/dl, respectively; P < 0.005), and the mean integrated IR-cortisol responses (588 ±115 and 976 ± 95 jtgmir/ dl, respectively; P < 0.01) were greater in the afternoon. There was an inverse correlation between basal plasma IRr cortisol concentration and the integrated IR-ACTH response (P < 0.05), the maximum IR-cortisol increment (P < 0.001), and the integrated IR-cortisol response (P < 0.001). We conclude that both plasma IR-ACTH and IR-cortisol responses to oCRH vary inversely with the basal plasma cortisol concentration and that, although the time of administration of oCRH does not have a major influence on the plasma IR-ACTH response, the plasma IR-cortisol response is much greater, to oCRH given in the late afternoon or evening than to oCRH given in the morning.