Peptides.Vol. 13, pp. 843-846, 1992
0196-9781/92 $5.00 + .00 Copyright © 1992 Pergamon Press Ltd.
Printed in the USA.
BRIEF COMMUNICATION
Intravenously Infused Substance P Enhances Basal and Growth Hormone (GH) Releasing Hormone-Stimulated GH Secretion in Normal Me,n V. C O I R O , * l R. V O L P I , * L. C A P R E T T I , t G . S P E R O N I , t R. B O C C H I , * G. C A F F A R R I , ~ R. COLLA,:I: G . R O S S I I : A N D P. C H I O D E R A *
*Department of Internal Medicine, School of Medicine, University of Parma, Parma, Italy, ?Endocrine Unit, Hospital of Codogno, Codogno, Italy, and ~Biochemistry Laboratory, Hospital of Guastalla Guastalla, Italy R e c e i v e d 19 D e c e m b e r 1991 COIRO, V., R. VOLPI, L. CAPRETTI, G. SPERONI, R. BOCCHI, G. CAFFARRI, R. COLLA, G. ROSS! AND P. CHIODERA.
Intravenously infitsed substance P enhances basal and growth hormone (GH) releasing hormone-stimulated GH secretion in normal men. PEPTIDES 13(4) 843-846, 1992.--The effect of synthetic substance P (SP), infused intravenously (IV) in doses of 0.5, 1, or 1.5 pmol/kg Vmin-' over 60 min, on GH secretion was evaluated in seven healthy men. Substance P tests and a control test with normal saline were randomly performed at weekly intervals. No untoward side effects or changes in blood pressure were observed during SP infusions. Serum GH concentrations did not change when normal saline, the lowest dose, or the middle close of SP were infused. In contrast, GH levels rose significantly when the highest dose of SP was given, with a mean peak two times higher than baseline. Further studies were performed to test the possible influence of SP on the GH response to GH-RH. For this purpose, seven other healthy men were tested with GH-RH (1 ~g/kg body weight in an IV bolus) during saline or SP (1.5 pmol/ Kg-Vmin -~ x 60 min) infusion. The GH-RH induced a significant GH rise, with a mean peak seven times higher than baseline. When subjects were infused with SP, the GH response to GH-RH was greatly enhanced, with a mean peak 12 times higher than baseline. These results demonstrate for the first time in humans that the systemic infusion of SP stimulates GH secretion, and suggest that SP might interact with GH-RH in the stimulation of GH secretion. Substance P
Growth hormone
Growth hormone releasing hormone
T H E undecapeptide substance P (SP) has been isolated and characterized from hypothalamic extracts (1). Further studies have shown that at the hypothalamic level, SP exerts potent effects as neurotransmitter and/or neuromodulator in the regulation of pituitary function (1). Various in vivo and in vitro studies in rats provided evidence of important influences of SP in the control of growth h o r m o n e (GH) secretion. While both stimulating and inhibiting effects on G H secretion have been reported after intraventricular injections of SP ( 1), the systemic administration of SP has been reported to stimulate G H release ( 1).
At present, the influence of SP on G H secretion in humans is unknown. Therefore, in the present study we examined whether an intravenous infusion of SP modifies basal and G H releasing hormone (GH-RH)-stimulated G H secretion in normal male subjects. In order to avoid SP-related stressful side effects, SP was infused in amounts that have been found to be well tolerated by human subjects (1 1). METHOD Seven healthy men, aged 24-34 years, participated in the study. The subjects were informed of the purpose of the study
Requests for reprints should be addressed to Vittorio Coiro, MD, Clinica Medica Generale e Terapia Medica, Universit~ di Parma, Via A. Gramsci 14, 1-43100 Parma, Italy.
843
844
COIRO ET AL. SP iNFUSION or SALINE
-~
~
~'
~
~o ,1~ ~
~)
%
eo ~M..
FIG. I. Effects of intravenous infusion of 0.5 (e . . . . e), 1,0 (11- II), 1.5 pmol/kg-t/ rain -j (e - - o) substance P or saline (O - - - O) in seven normal men. Each point represents the mean _+SE of the obser,¢ations.
and gave their informed consent. The study was in accordance with the Helsinki II declaration. All men were in good health, without clinical and laboratory evidence of hepatic, renal, heart, or other organic disease. All subjects were within 10% of their ideal body weight. None of them was a smoker or was addicted to an excessive alcohol consumption (
0196-9781/92 $5.00 + .00 Copyright © 1992 Pergamon Press Ltd.
Printed in the USA.
BRIEF COMMUNICATION
Intravenously Infused Substance P Enhances Basal and Growth Hormone (GH) Releasing Hormone-Stimulated GH Secretion in Normal Me,n V. C O I R O , * l R. V O L P I , * L. C A P R E T T I , t G . S P E R O N I , t R. B O C C H I , * G. C A F F A R R I , ~ R. COLLA,:I: G . R O S S I I : A N D P. C H I O D E R A *
*Department of Internal Medicine, School of Medicine, University of Parma, Parma, Italy, ?Endocrine Unit, Hospital of Codogno, Codogno, Italy, and ~Biochemistry Laboratory, Hospital of Guastalla Guastalla, Italy R e c e i v e d 19 D e c e m b e r 1991 COIRO, V., R. VOLPI, L. CAPRETTI, G. SPERONI, R. BOCCHI, G. CAFFARRI, R. COLLA, G. ROSS! AND P. CHIODERA.
Intravenously infitsed substance P enhances basal and growth hormone (GH) releasing hormone-stimulated GH secretion in normal men. PEPTIDES 13(4) 843-846, 1992.--The effect of synthetic substance P (SP), infused intravenously (IV) in doses of 0.5, 1, or 1.5 pmol/kg Vmin-' over 60 min, on GH secretion was evaluated in seven healthy men. Substance P tests and a control test with normal saline were randomly performed at weekly intervals. No untoward side effects or changes in blood pressure were observed during SP infusions. Serum GH concentrations did not change when normal saline, the lowest dose, or the middle close of SP were infused. In contrast, GH levels rose significantly when the highest dose of SP was given, with a mean peak two times higher than baseline. Further studies were performed to test the possible influence of SP on the GH response to GH-RH. For this purpose, seven other healthy men were tested with GH-RH (1 ~g/kg body weight in an IV bolus) during saline or SP (1.5 pmol/ Kg-Vmin -~ x 60 min) infusion. The GH-RH induced a significant GH rise, with a mean peak seven times higher than baseline. When subjects were infused with SP, the GH response to GH-RH was greatly enhanced, with a mean peak 12 times higher than baseline. These results demonstrate for the first time in humans that the systemic infusion of SP stimulates GH secretion, and suggest that SP might interact with GH-RH in the stimulation of GH secretion. Substance P
Growth hormone
Growth hormone releasing hormone
T H E undecapeptide substance P (SP) has been isolated and characterized from hypothalamic extracts (1). Further studies have shown that at the hypothalamic level, SP exerts potent effects as neurotransmitter and/or neuromodulator in the regulation of pituitary function (1). Various in vivo and in vitro studies in rats provided evidence of important influences of SP in the control of growth h o r m o n e (GH) secretion. While both stimulating and inhibiting effects on G H secretion have been reported after intraventricular injections of SP ( 1), the systemic administration of SP has been reported to stimulate G H release ( 1).
At present, the influence of SP on G H secretion in humans is unknown. Therefore, in the present study we examined whether an intravenous infusion of SP modifies basal and G H releasing hormone (GH-RH)-stimulated G H secretion in normal male subjects. In order to avoid SP-related stressful side effects, SP was infused in amounts that have been found to be well tolerated by human subjects (1 1). METHOD Seven healthy men, aged 24-34 years, participated in the study. The subjects were informed of the purpose of the study
Requests for reprints should be addressed to Vittorio Coiro, MD, Clinica Medica Generale e Terapia Medica, Universit~ di Parma, Via A. Gramsci 14, 1-43100 Parma, Italy.
843
844
COIRO ET AL. SP iNFUSION or SALINE
-~
~
~'
~
~o ,1~ ~
~)
%
eo ~M..
FIG. I. Effects of intravenous infusion of 0.5 (e . . . . e), 1,0 (11- II), 1.5 pmol/kg-t/ rain -j (e - - o) substance P or saline (O - - - O) in seven normal men. Each point represents the mean _+SE of the obser,¢ations.
and gave their informed consent. The study was in accordance with the Helsinki II declaration. All men were in good health, without clinical and laboratory evidence of hepatic, renal, heart, or other organic disease. All subjects were within 10% of their ideal body weight. None of them was a smoker or was addicted to an excessive alcohol consumption (
