Journal of Clinical Endocrinology & Metabolism, Vol 81, 909-913, Copyright © 1996 by Endocrine Society

ARTICLES

Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli

R Peino, F Cordido, A Penalva, CV Alvarez, C Dieguez and FF Casanueva
Department of Medicine, School of Medicine, Santiago de Compostela University, Spain.

Increases in plasma free fatty acids (FFA) inhibit the GH response to a variety of stimuli; however, the role of FFA depression in GH control is far from understood. In the present work, FFA reduction was obtained by the administration to normal subjects of acipimox, a lipid-lowering drug devoid of side-effects. Each subject tested underwent two paired tests. In one, acipimox was administered orally at a dose of 250 mg at - 270 min and at a dose of 250 mg at -60 min; in the matched test, placebo was given at similar intervals. To induce GH release, four stimuli acting through different mechanisms were used: pyridostigmine (120 mg, orally) at -60 min, GHRH (1 microgram/kg, iv) at 0 min, GH- releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; 1 microgram/kg, iv) at 0 min, and finally, GHRH plus GHRP-6 at the same doses at 0 min. GH secretion was analyzed as the area under the secretory curve (AUC; mean +/- SE, micrograms per L/120 min). Acipimox pretreatment alone (n = 6) induced a reduction in FFA levels compared with placebo treatment. The FFA reduction led to a sustained GH secretion that increased from 2.4 +/- 1.8 micrograms/L at -120 min to 14.2 +/- 4.0 at 120 min. The GH AUC for placebo was 266 +/- 100, and that for acipimox was 1781 +/- 408 (P < 0.05). In the pyridostigmine- treated group (n = 6), the acipimox-pyridostigmine AUC (2046 +/- 323) was higher (P < 0.05) than the placebo-pyridostigmine AUC (764 +/- 101), but was not different from the AUC of acipimox alone. Previous FFA reduction nearly doubled the GHRH-mediated GH secretion (n = 6; placebo-GHRH AUC, 1817 +/- 365; acipimox-GHRH test, 3228 +/- 876; P < 0.05). A similar enhancement was observed when the stimulus employed was GHRP-6 (n = 6; placebo-GHRP-6 AUC, 2034 +/- 295; acipimox-GHRP-6, 4827 +/- 703; P < 0.05). Furthermore, even the most potent GH stimulus known to date, i.e. GHRH plus GHRP-6, was enhanced by the FFA suppression (placebo-GHRH-GHRP-6 AUC, 2034 +/- 277; acipimox-GHRH-GHRP- 6, 5809 +/- 758; P < 0.05). The enhancing effect of lowering FFA levels was additive regardless of the stimulus employed. These results indicate that 1) FFA reduction per se stimulates GH secretion with a delayed time of action; 2) FFA reduction enhanced in an additive manner the GH secretion elicited by such different stimuli as pyridostigmine, GHRH, and GHRP-6; and 3) the observation that FFA reduction enhanced the response to the most potent GH stimulus, GHRH plus GHRP-6, suggests that FFA suppression acts by a separate mechanism. FFA reduction may have value in the clinical setting for assessing GH reserve.

This article has been cited by other articles:

				K. A. Stokes, C. Tyler, and K. L. Gilbert The growth hormone response to repeated bouts of sprint exercise with and without suppression of lipolysis in men J Appl Physiol, March 1, 2008; 104(3): 724 - 728. [Abstract] [Full Text] [PDF]

				X.-D. Qu, I. T. Gaw Gonzalo, M. Y. Al Sayed, P. Cohan, P. D. Christenson, R. S. Swerdloff, D. F. Kelly, and C. Wang Influence of Body Mass Index and Gender on Growth Hormone (GH) Responses to GH-Releasing Hormone Plus Arginine and Insulin Tolerance Tests J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1563 - 1569. [Abstract] [Full Text] [PDF]

				S. Nielsen, N. Moller, J. S. Christiansen, and J. O.L. Jorgensen Pharmacological Antilipolysis Restores Insulin Sensitivity During Growth Hormone Exposure Diabetes, October 1, 2001; 50(10): 2301 - 2308. [Abstract] [Full Text]

				N. Briard, M. Rico-Gomez, V. Guillaume, N. Sauze, V. Vuaroqueaux, F. Dadoun, Y. Le Bouc, C. Oliver, and A. Dutour Hypothalamic Mediated Action of Free Fatty Acid on Growth Hormone Secretion in Sheep Endocrinology, December 1, 1998; 139(12): 4811 - 4819. [Abstract] [Full Text] [PDF]

				A. Leal-Cerro, L. M. Jimenez, R. Astorga, I. Fernandez-Lopez, C. Dieguez, and F. F. Casanueva Acute Pharmacological Reduction of Plasma Free Fatty Acids Enhances the Growth Hormone (GH)-Releasing Hormone-Mediated GH Secretion in Patients with Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 3165 - 3168. [Abstract] [Full Text] [PDF]

				R. Lanzi, M. F. Manzoni, A. C. Andreotti, M. E. Malighetti, E. Bianchi, L. P. Sereni, A. Caumo, L. Luzi, and A. E. Pontiroli Evidence for an Inhibitory Effect of Physiological Levels of Insulin on the Growth Hormone (GH) Response to GH-Releasing Hormone in Healthy Subjects J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2239 - 2243. [Abstract] [Full Text] [PDF]

				F. R. Perez, X. Casabiell, J. P. Camina, J. L. Zugaza, and F. F. Casanueva cis-Unsaturated Free Fatty Acids Block Growth Hormone and Prolactin Secretion in Thyrotropin-Releasing Hormone-Stimulated GH3 Cells by Perturbing the Function of Plasma Membrane Integral Proteins Endocrinology, January 1, 1997; 138(1): 264 - 272. [Abstract] [Full Text] [PDF]