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Evidence for a Limited Growth Hormone (GH)-Releasing Hormone (GHRH)-Releasable Quantity of GH: Effects of 6-Hour Infusions of GHRH on GH Secretion in Normal Man^*

Department of Internal Medicine, University of Virginia Medical Center Charlottesville, Virginia 2290
The Children's Hospital of Philadelphia, University of Pennsylvan Philadelphia, Pennsylvania 19104;
The Peptide Biology Laboratory, Salk Institue San Diego, California 92138-921
and the Department of Internal Medicine, University of Cincinnati Medical Center Cincinnati, Ohio 45267

Address requests for reprints to: Dr. Michael O. Thorner, Box 511, University of Virginia Medical Center, Charlottesville, Virginia 22908.

Human GH-releasing hormone [hGHRH-40 (GHRH)] stimulates GH release in a dose-dependent fashion when administered as single iv bolus doses or as continuous 90-min infusions. However, there has been variability in the GH responses, and it appears that there are waxing and waning effects of GHRH. To address whether these are a result of the dose of GHRH, time, or intermittent changes in sensitivity of the somatotrophs, we administered 6-h infusions of vehicle and different doses of GHRH to six normal men. In addition, an iv bolus injection of GHRH was given after 5.5 h of infusion to evaluate residual GH secretory capacity. The subjects were given infusions of either vehicle or GHRH (1, 3.3, and 10 ng/kg-min), followed by an iv bolus injection of 3.3 µg/kg on four separate occasions. GHRH infusions stimulated GH secretion compared to basal secretion. The changes from basal GH secretion (mean ± SEM) were 2.0 ± 1.6, 4.6 ± 1.5, 12.7 ± 5.1, and 8.2 ± 1.8 ng/ ml-h during the vehicle and GHRH (1, 3.3, and 10 ng/kg-min) infusions, respectively. The changes from basal GH secretion for 2 h after the iv bolus dose (after 5.5 h of infusion) were 33.3 ± 8.7, 22.4 ± 3.8, 14.0 ± 3.6, and 10.5 ± 2.0 ng/mlh on the vehicle and GHRH (1, 3.3, and 10 ng/kg-min) infusion days, respectively. The magnitude of the GH response was inversely related to the GHRH infusion dose. The total amount of GH released during the 7.5-h study periods was not different among the vehicle and 3 GHRH infusion days. Thus, it appears that a finite amount of GH is released by GHRH. There was variability in the degree of responsiveness to the continuous infusions of GHRH. Surges of GH release occurred during the GHRH infusions, which may be attributed to intermittent secretion of a GH inhibitor, such as somatostatin.

^* This work was supported by USPHS grants: New Investigator Award IR23-HD-17120 (to M.L.V.); AM-32632 and RR-00847 (to M.O.T.); AM-26741 (to J.R. and W.V.); and AM-30667, AM-18722 and RR-0068 (to L.A.F.)

Received August 24, 1984.

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