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Journal of Clinical Endocrinology & Metabolism Vol. 61, No. 2 273-279
doi:10.1210/jcem-61-2-273
Copyright © 1985 by the Endocrine Society.
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Diurnal Variation in the Response of Plasma Adrenocorticotropin and Cortisol to Intravenous Ovine Corticotropin-Releasing Hormone*

G. STEPHEN DECHERNEY{dagger}, C. ROWAN DEBOLD{ddagger}, RICHARD V. JACKSON§, WILLIAM R. SHELDON||, DONALD P. ISLAND and DAVID N. ORTH

Department of Medicine, Vanderbilt University School of Medicine Nashville, Tennessee 37232

Address all correspondence to: Dr. David N. Orth, A4215 Vanderbilt Medical Center North, Nashville, Tennessee 37232

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.

* This work was supported in part by USPHS Research Grants 1-R01-AM-33334 from the NIADDK, 5-M01-RR-00095 from the General Research Centers Branch of the NIH, and 5-R01-CA-11685 from the NCL

{dagger} Recipient of National Research Fellowship Award 2-F32-AM-06758 from the NIADDK. Present address: Building 10, Room 8N323,National Institutes of Health, Bethesda, Maryland 20205.

{ddagger} TRecipient of National Research Fellowship Award 5-F32-CA-06939 from the NCI and a Clinical Associate Physician of the Vanderbilt Clinical Research Center (RR-00095).

§ Applied Health Sciences Fellow, National Health and MedicalResearch Council of Australia. Present address: Department of Medicine, University of Queensland, Greenslopes Hospital, Brisbane, Australia 4120.

|| Recipient of a Fellowship Award from Research Training in Diabetes and Endocrinology Grant 5-T32-AM-07061. Present address: Medical and Surgical Clinic Association, 1200 Summit, Suite 120, Fort Worth, Texas 76107.

Received January 14, 1985.




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