Suppression of growth hormone (GH) hypersecretion due to ectopic GH-releasing hormone (GHRH) by a selective GHRH antagonist.
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 i.v. 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 micrograms/kg, i.v.) acutely suppressed GH concentration to 30-40% of the pretreatment baseline, and this effect lasted 3-4 h. Administration of GHRH (0.33 microgram/kg, i.v.) bolus resulted in a small rise in GH, and this effect was blocked by GHRH-Ant (400 micrograms/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.
Jaffe
C A
CA
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan, USA.
DeMott-Friberg
R
R
Frohman
L A
LA
Barkan
A L
AL
D000172:Acromegaly / Q000209:etiology / Q000378:metabolism; D000328:Adult; D002276:Carcinoid Tumor / Q000209:etiology / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D011673:Pulsatile Flow; D013997:Time Factors
D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone