J. Endocrinol. Invest. 13: 539-542, 1990
COMMENT
Effect of acipimox, a lipid lowering drug, on growth hormone (GH) response to GH-releasing hormone in normal subjects A.E. Pontiroli, R. Lanzi, LD. Monti, and G. Pozza Istituto Scientifico San Raffaele, Cattedra di Clinica Medica, Universita degli Studi di Milano, 20132 Milano, Italy ABSTRACT. Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GHreleasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 jlg iv The GH
response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo. In subjects receiving placebo, but not in those receiving acipimox, a progressive increase of plasma FFA levels took place, and the GH response to GHRH was inversely related to the plasma FFA levels at 0 min. These data indicate that FFA play an important role in the control of GH release, and that acipimox prevents the FFA rise induced by GH.
INTRODUCTION The release of growth hormone (GH) is regulated by two hypothalamic hormones, somatostatin, inhibitory, and GH-releasing hormone (GHRH), stimulatory, acting at the pituitary level (1). Once released, GH induces lipolysis with an increase in plasma free fatty acids (FFA) (2), and FFA have been shown to inhibit the GH response to arginine and to GHRH (3-5); this suggests the existence of a FFA feedback contra I of GH release. Therefore, a reduction of plasma FFA should enhance GH release; as a matter of fact, previous studies have shown that acute suppression of FFA, obtained by iv administration of nicotinic acid, was followed by a spontaneous GH release (6,7), and that long term administration of clofibrate enhances the GH response to arginine (8). Since all these studies were performed before GHRH was available (9), the aim of the present study was to examine the effect of pharmacologic blockade of lipolysis on the GH response to GHRH in normal subjects.
MATERIALS AND METHODS The protocol of the study was approved by the Ethical Committee of Istituto Scientifico San Raffaele, and all subjects gave written informed consent before entering the study, Eleven healthy men, aged 24-26 yr, free of endocrine and metabolie disorders, in good health as ascertained by story, physical and routine laboratory examinations, ehest X-ray, and baseline evaluation of serum GH, prolactin, cortisol, glucagon, and insulin levels, entered the study, All subjeets started a slow 0,9% NaCI infusion at 09:00 hand reeeived at time 0 min, at 13:00 h, GHRH (1-44,50 jlg iv) and blood sampling for evaluation of serum GH levels was performed at various time intervals as shown in Figure 1. Ten men received randomly one of the two pretreatments: 1)acipimox (10,11), 250 mg at 07:00 hand at 11 :00 h; 2) placebo at 07:00 and at 11 :OOh; the eleventh man underwent both tests. At 2-h intervals, blood glucose, serum insulin, and plasma FFA and somatomedin C (IGF-I) levels were also determined, as shown in Figure 2. The men were fasted overnight and refrained from smoking, and the tests were performed in the recumbent position. No severe side effects were observed during the tests: a moderate facial skin flush was the complaint of 2/6 subjects only after the first, but not after the second capsule of acipimox.
Key-words: Growth hormone, GHRH, lree latty acids (FFA, NEFA), acipimox. Correspondence: AE. Pontiroli, Istituto San Raffaele, Via Olgettina 60, 20132 Milano, Italy. Received March 15,1989; accepted February 12,1990.
539
A. E. Pantiroli, R. Lanzi, L. D. Manti, et al.
GHRH Cl-44)50}Jg LV.
60
..::!. 0\
40
:x:
Cl J:
}Jg/L
0
PLACEBO/ PLACEBO/ ACIPIMOX ACIPIMOX
+
p
COMMENT
Effect of acipimox, a lipid lowering drug, on growth hormone (GH) response to GH-releasing hormone in normal subjects A.E. Pontiroli, R. Lanzi, LD. Monti, and G. Pozza Istituto Scientifico San Raffaele, Cattedra di Clinica Medica, Universita degli Studi di Milano, 20132 Milano, Italy ABSTRACT. Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GHreleasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 jlg iv The GH
response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo. In subjects receiving placebo, but not in those receiving acipimox, a progressive increase of plasma FFA levels took place, and the GH response to GHRH was inversely related to the plasma FFA levels at 0 min. These data indicate that FFA play an important role in the control of GH release, and that acipimox prevents the FFA rise induced by GH.
INTRODUCTION The release of growth hormone (GH) is regulated by two hypothalamic hormones, somatostatin, inhibitory, and GH-releasing hormone (GHRH), stimulatory, acting at the pituitary level (1). Once released, GH induces lipolysis with an increase in plasma free fatty acids (FFA) (2), and FFA have been shown to inhibit the GH response to arginine and to GHRH (3-5); this suggests the existence of a FFA feedback contra I of GH release. Therefore, a reduction of plasma FFA should enhance GH release; as a matter of fact, previous studies have shown that acute suppression of FFA, obtained by iv administration of nicotinic acid, was followed by a spontaneous GH release (6,7), and that long term administration of clofibrate enhances the GH response to arginine (8). Since all these studies were performed before GHRH was available (9), the aim of the present study was to examine the effect of pharmacologic blockade of lipolysis on the GH response to GHRH in normal subjects.
MATERIALS AND METHODS The protocol of the study was approved by the Ethical Committee of Istituto Scientifico San Raffaele, and all subjects gave written informed consent before entering the study, Eleven healthy men, aged 24-26 yr, free of endocrine and metabolie disorders, in good health as ascertained by story, physical and routine laboratory examinations, ehest X-ray, and baseline evaluation of serum GH, prolactin, cortisol, glucagon, and insulin levels, entered the study, All subjeets started a slow 0,9% NaCI infusion at 09:00 hand reeeived at time 0 min, at 13:00 h, GHRH (1-44,50 jlg iv) and blood sampling for evaluation of serum GH levels was performed at various time intervals as shown in Figure 1. Ten men received randomly one of the two pretreatments: 1)acipimox (10,11), 250 mg at 07:00 hand at 11 :00 h; 2) placebo at 07:00 and at 11 :OOh; the eleventh man underwent both tests. At 2-h intervals, blood glucose, serum insulin, and plasma FFA and somatomedin C (IGF-I) levels were also determined, as shown in Figure 2. The men were fasted overnight and refrained from smoking, and the tests were performed in the recumbent position. No severe side effects were observed during the tests: a moderate facial skin flush was the complaint of 2/6 subjects only after the first, but not after the second capsule of acipimox.
Key-words: Growth hormone, GHRH, lree latty acids (FFA, NEFA), acipimox. Correspondence: AE. Pontiroli, Istituto San Raffaele, Via Olgettina 60, 20132 Milano, Italy. Received March 15,1989; accepted February 12,1990.
539
A. E. Pantiroli, R. Lanzi, L. D. Manti, et al.
GHRH Cl-44)50}Jg LV.
60
..::!. 0\
40
:x:
Cl J:
}Jg/L
0
PLACEBO/ PLACEBO/ ACIPIMOX ACIPIMOX
+
p
