Blunted growth hormone (GH) responsiveness to GH-releasing hormone in obese patients: influence of prolonged administration of the serotoninergic drug fenfluramine.
The aim of the present study was to ascertain if reduced central serotoninergic activity might contribute to the well-known blunted growth hormone (GH) response to GH-releasing hormone (GHRH) in obese patients. Thus, we studied the effect of prolonged stimulation of the serotoninergic system by fenfluramine (FF; 60 mg twice daily for 7 days) on GHRH-induced GH release in nine obese and seven normal subjects. In controls, GHRH (100 micrograms intravenously [IV]) injection increased GH levels from 2.3 +/- 1.8 (+/- SE) to 18.5 +/- 2.8 mU/L, P less than .002. FF administration enhanced both basal and GHRH-stimulated GH levels (peak, 38.4 +/- 8.3 v 6.9 +/- 2.6 mU/L, P less than .002). This response was significantly higher (P less than .02) than in pretreatment. In obese patients, GH responsiveness to GHRH was slight (peak, 7.1 +/- 2.0 v 0.6 +/- 0.18 mU/L, P less than .01) and lower (P less than .01) than in controls. FF administration did not affect this response. In controls, the enhanced FF-induced GH release after a maximal dose of GHRH indicates that serotoninergic activation influences GH secretion and that the mechanism involved is independent of endogenous GHRH. In obese patients, we found a blunted GH responsiveness to GHRH that was not affected by FF, thus supporting the hypothesis that the serotoninergic control on GH release is impaired.
Argenio
G F
GF
Istiuto di Clinica Medica, University of Pisa, Italy.
Bernini
G P
GP
Sgró
M
M
Vivaldi
M S
MS
Del Corso
C
C
Santoni
R
R
Franchi
F
F
D000328:Adult; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012016:Reference Values; D013997:Time Factors
D007328:Insulin; D005277:Fenfluramine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone