Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome

M. Procopio, C. Invitti, M. Maccario, S. Grottoli, F. Cavagnini, F. Camanni, E. Ghigo

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Gushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release. DESIGN: Three tests with GHRH alone (1 μg/kg iv at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 ± 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 ± 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 ± 0.3 Kg/m2) were studied as controls (C). MEASUREMENTS: Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (μg/L) or as areas under the curve (AUG, μg/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (μg/L) with reference to a pure recombinant ICE-I preparation. RESULTS: Basal GH levels in CS were similar to those registered in OB (mean ± s.e.m. 0.7 ± 0.1 vs 0.9 ± 0.2 μg/L) and lower than in C (3.4 ± 0.5 μg/L, P <0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 ± 13.2 vs 192.5 ± 61.7 μg/L/h) and both GH responses were significantly lower than that of C (1029.9 ± 98.0 ug/L/h, P <0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 ± 51.9 μg/L/h vs GHRH alone, P <0.0001), OB (852.4 ± 162.1 μg/L/h, P <0.0001) and C (3362.6 ± 386.0 μg/L/h, P <0.0002). However, the GH response to GHRH 1 plus ARG in CS was lower (P <0.002) than that in OB which, in turn, was lower than that in C (P <0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 ± 221.2 μg/L/h, P <0.00001) and, to a lesser extent, in OB (627.3 ± 84.7 μg/L/h, P <0.0002) but not in CS (102.9 ± 25.0 μg/L/h). CONCLUSIONS: Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Gushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.

Original languageEnglish
Pages (from-to)108-112
Number of pages5
JournalInternational Journal of Obesity
Volume19
Issue number2
Publication statusPublished - 1995

Fingerprint

Pyridostigmine Bromide
Cushing syndrome
Growth Hormone-Releasing Hormone
Cushing Syndrome
somatotropin
Growth Hormone
arginine
Arginine
obesity
Obesity
hormones
Insulin-Like Growth Factor I
Hormones
insulin-like growth factor I
Adrenocorticotropic Hormone
Area Under Curve
corticotropin
Somatostatin
somatoliberin
Radioimmunoassay

Keywords

  • Arginine
  • Cushing's syndrome
  • GH
  • GHRH
  • Obesity
  • Pyridostigmine

ASJC Scopus subject areas

  • Food Science
  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Public Health, Environmental and Occupational Health

Cite this

Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome. / Procopio, M.; Invitti, C.; Maccario, M.; Grottoli, S.; Cavagnini, F.; Camanni, F.; Ghigo, E.

In: International Journal of Obesity, Vol. 19, No. 2, 1995, p. 108-112.

Research output: Contribution to journalArticle

Procopio, M. ; Invitti, C. ; Maccario, M. ; Grottoli, S. ; Cavagnini, F. ; Camanni, F. ; Ghigo, E. / Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome. In: International Journal of Obesity. 1995 ; Vol. 19, No. 2. pp. 108-112.
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T1 - Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome

AU - Procopio, M.

AU - Invitti, C.

AU - Maccario, M.

AU - Grottoli, S.

AU - Cavagnini, F.

AU - Camanni, F.

AU - Ghigo, E.

PY - 1995

Y1 - 1995

N2 - OBJECTIVES: The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Gushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release. DESIGN: Three tests with GHRH alone (1 μg/kg iv at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 ± 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 ± 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 ± 0.3 Kg/m2) were studied as controls (C). MEASUREMENTS: Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (μg/L) or as areas under the curve (AUG, μg/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (μg/L) with reference to a pure recombinant ICE-I preparation. RESULTS: Basal GH levels in CS were similar to those registered in OB (mean ± s.e.m. 0.7 ± 0.1 vs 0.9 ± 0.2 μg/L) and lower than in C (3.4 ± 0.5 μg/L, P <0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 ± 13.2 vs 192.5 ± 61.7 μg/L/h) and both GH responses were significantly lower than that of C (1029.9 ± 98.0 ug/L/h, P <0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 ± 51.9 μg/L/h vs GHRH alone, P <0.0001), OB (852.4 ± 162.1 μg/L/h, P <0.0001) and C (3362.6 ± 386.0 μg/L/h, P <0.0002). However, the GH response to GHRH 1 plus ARG in CS was lower (P <0.002) than that in OB which, in turn, was lower than that in C (P <0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 ± 221.2 μg/L/h, P <0.00001) and, to a lesser extent, in OB (627.3 ± 84.7 μg/L/h, P <0.0002) but not in CS (102.9 ± 25.0 μg/L/h). CONCLUSIONS: Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Gushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.

AB - OBJECTIVES: The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Gushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release. DESIGN: Three tests with GHRH alone (1 μg/kg iv at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 ± 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 ± 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 ± 0.3 Kg/m2) were studied as controls (C). MEASUREMENTS: Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (μg/L) or as areas under the curve (AUG, μg/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (μg/L) with reference to a pure recombinant ICE-I preparation. RESULTS: Basal GH levels in CS were similar to those registered in OB (mean ± s.e.m. 0.7 ± 0.1 vs 0.9 ± 0.2 μg/L) and lower than in C (3.4 ± 0.5 μg/L, P <0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 ± 13.2 vs 192.5 ± 61.7 μg/L/h) and both GH responses were significantly lower than that of C (1029.9 ± 98.0 ug/L/h, P <0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 ± 51.9 μg/L/h vs GHRH alone, P <0.0001), OB (852.4 ± 162.1 μg/L/h, P <0.0001) and C (3362.6 ± 386.0 μg/L/h, P <0.0002). However, the GH response to GHRH 1 plus ARG in CS was lower (P <0.002) than that in OB which, in turn, was lower than that in C (P <0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 ± 221.2 μg/L/h, P <0.00001) and, to a lesser extent, in OB (627.3 ± 84.7 μg/L/h, P <0.0002) but not in CS (102.9 ± 25.0 μg/L/h). CONCLUSIONS: Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Gushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.

KW - Arginine

KW - Cushing's syndrome

KW - GH

KW - GHRH

KW - Obesity

KW - Pyridostigmine

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