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Suppression of Growth Hormone (GH) Hypersecretion due to Ectopic GH-Releasing Hormone (GHRH) by a Selective GHRH Antagonist¹

Department of Internal Medicine, Divisions of Endocrinology and Metabolism (C.A.J., R.D.-F., A.L.B), Department of Veterans Affairs Medical Center and University of Michigan Medical Center, Ann Arbor, Michigan 48109; and the Department of Internal Medicine, University of Illinois (L.A.F.), Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Craig A. Jaffe, M.D., Division of Endocrinology and Metabolism, 3920 Taubman Center, Box 0354, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0354.

Abstract

We have recently demonstrated that a competitive antagonist of GHRH, (N-Ac-Tyr¹,D-Arg²)GHRH-(1–29)NH₂ (GHRH-Ant), eliminates nearly all nocturnal GH pulsatility in normal subjects, supporting the hypothesis that GH pulsatility is driven by GHRH. In this study, we compared the effects of every 12 h iv boluses of either GHRH-Ant or saline on 24-h GH profiles in a patient with acromegaly due to a metastatic GHRH-secreting carcinoid tumor. Bolus doses of GHRH-Ant (400 µg/kg, iv) acutely suppressed GH concentration to 30–40% of the pretreatment baseline, and this effect lasted 3–4 h. Administration of GHRH (0.33 µg/kg, iv) bolus resulted in a small rise in GH, and this effect was blocked by GHRH-Ant (400 µg/kg). During saline treatment, the secretory patterns of both GH and ectopic GHRH were pulsatile; however, there was no correlation between changes in plasma GHRH and GH concentrations. This lack of correlation was probably due to the majority of circulating GHRH immunoreactivity consisting of nonbiologically active GHRH fragments. These data support the hypothesis that GH hypersecretion in the ectopic GHRH syndrome requires GHRH receptor occupancy and validates the use of GHRH-Ant to probe the potential involvement of endogenous GHRH in patients with acromegaly due to pituitary somatotropinoma.

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