397
Growth Hormone Release After the Sequential Use of Growth Hormone Releasing Factor and Exercise J. H. de Vries, R. J. P. Noorda, G. A. Voetberg and E. A. van der Veen Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands
Introduction
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Growth hormone (GH) secretion is under dual control of Growth Hormone Releasing Factor (GRF) and somatostatin. Whereas low or even non-detectable values are physiological in at random blood samples of normal individuals, several stimuli are used to evaluate the pituitary capacity to secrete GH: insulin-hypoglycemia, arginine, L-DOPA, sleep, exercise and GRF. Since an absent response to one stimulus does not exclude response to another, it is recommended to perform at least two tests when evaluating pituitary reserve (Davies and Johnston 1987). All stimuli but sleep, exercise and GRF are unpleasant to the subject tested. The sleeptest is difficult to perform in an outpatient setting. To determine whether the GRF and exercise stimulus influence each other when performed shortly after each other, we measured Growth Hormone response to a bolus of GRF followed by exercise and vice versa. Subjects and Methods Subjects studied were five healthy young men, mean age 24 (range 22 to 29) years. They were within 15 % limits of normal body weight, used no medication and a normal diet. Informed consent was obtained in advance of the study. After an overnight fast an i. v. cannula was inserted. After 30 minutes rest (t = 0) a bolus of 100 u,g of human pancreatic growth hormone releasing factor 1-44 (hpGRF 1-44) (Somatobiss, Bissendorf Peptide) was administered. Blood samples for the determination of GH were drawn at t = - 15, 0, 10, 20, 30, 40, 50, 60 and 70 minutes. On t = 170 the subjects started exercising for 20 minutes on a bicycle ergometer against a load of 100 W. Blood samples were drawn at t = 150, 170, 180, 185, 190, 200 and 205 minutes (testsequence 1). Two weeks later testing was repeated in reversed sequence (testsequence 2). Exercise was performed for 20 minutes, two hours later (t= 140) the bolus of GRF was administered. Blood samples were drawn at t = - 15, 0, 10, 15,20, 25, 30, 35, 125, 140,150,160,170,180, 190,200 and 210 minutes. GH levels were determined by radioimmunoassay (Oris, France). The lowest detectable level of this assay is 0.5 ng/ml. The intra- and interassay coefficients of variation are 8.2% and 11.9% respectively. For statistical analysis Student's t-test for paired data was used.
Fig. 1 Top: Serum GH (ng/ml, mean + SEM) after 100 ug GRF i. v. followed by 20 minutes exercise (n = 5), Bottom: Serum GH (ng/ml, mean + SEM) during 20 minutes exercise followed by 100 ug GRF i.v. (n = 5).
Results Results of the first testsequence are depicted in Figure 1 (top). Mean basal level was 1.0 ng/ml (SEM 0.2). All subjects responded to the bolus of GRF, mean peak value being 24.6 ng/ml (SEM 6.8). The GH response to exercise after prior administration of GRF is absent. When performed in reversed order, the results are as
given in Figure 1 (bottom). All subjects reacted with a GH response to exercise, mean peak value response being 3.7 ng/ml (SEM 1.1). All subjects responded to subsequent injection of a bolus of GRF, but the mean response was lower than after GRF administration alone: 17.1 ng/ml (SEM 9.3) vs 24.6 ng/ml (p < 0.05).
Horm.metabol. Res. 23 (1991)397-398 © Georg Thieme Verlag Stuttgart • New York
Received: 24 July 1990
Accepted: 11 March 1991 after revision
Horm. metab. Res. 23 (1991)
J. H. de Bries, R.J. P. Noorda, G. A. Voetberg andE. A. van der Veen
Discussion This study shows that prior injection of a bolus of GRF abolishes the GH response to exercise and exercise attenuates the GH response to subsequent administration of abolus of GRF.
poglycemia directly inhibits somatostatin (Page, Koppeschaar, Edwards, Dieguez and Scanlon 1987). Our findings of an abolished response to exercise after GRF pretreatment do not support the hypothesized role of catecholamines in the inhibition of somatostatin.
Different mechanisms for the stimuli mentioned above probably explain why in a given subject the absence of GH reThat the subsequent administration of various lease to one stimulus does not exclude a response to another. Although stimuli influences GH response is reported several times. Four studies GRF and exercise are both stimuli that do not endanger, nor put excesshowed no or a distinctly diminished GH response following a second sive strain on the subject tested, it is probably better to use both a non bolus of GRF given shortly after a first one, a phenomenon ascribed to GRF dependent and a GRF dependent stimulus when evaluating desensitization of the somatotrophes or to a reactive somatostatin release in the portal circulation after the first bolus of GFR (Losa, Bock, pituitary reserve. Schopohl, Stalla, Muller and von Werder 1984; Shibasaki, Hotta, Masuda, Imaki, Obara, Demura, Ling and Shizume 1985; Sartorio, References Spada, Bochicchio, Atterrato, Morabito and Faglia 1986; Page, Dieguez, Valcavi, Edwards, Hall and Scanlon 1988). After pretreat- Davies,R.R.,D. G. Johnston:!. Roy. S. Med. 80:3-5 (1987) ment with GRF, Page et al. (1988) also found an abolished GH re- Losa, M., L. Bock, J. Schopohl, G. K. Stalla, 0. A. Muller, K. von Wersponse to L-DOPA, suggesting an endogenous GFR dependent mechrferActa Endocrinol. 107:462-470(1984) anism for L-DOPA: after desensitization of the somatotrophes by exo- Page, M. D., H P. E. Koppeschaar, C. A. Edwards, C. Dieguez, M. F. genous GRF the subsequent endogenous GRF rise induced by LScanlon:Clin. Endocrinol. 26: 589-595 (1987) DOPA does not result in GH release. Our findings with exercise as a Page, M. D., C. Dieguez, C. Valcavi, C. Edwards, R. Hall, M. F. Scansecond stimulus are similar, suggesting an endogenous GFR dependlon:C\in. Endocrinol. 28:551-558 (1988) ent mechanism for GH release after exercise as well. The significantly Sartorio, A., A. Spada, D. Bochicchio, A. Atterrato, F. Morabito, G. Falower GH response to GRF after prior exercise can be explained by glia.-Neuroendocr. 44:470-474 (1986) partial desensitization of the somatotrophes after the relative weak Shibasaki, T., M. Hotta, A. Masuda, T. Imaki, N. Obara, H. Demura, stimulus exercise or by a milder somatostatin release respectively. N. Ling, K. Shizume:J. Clin. Endocrinol. Metab. 60: 1265-1267 Another potential explanation for the observed lower GH secretion (1985) after a second stimulus is exhaustion of the somatotrophe. However, Shibasaki et al. (1985) found an enhanced GH response to insulin hypoglycemia after prior administration of GRF and Page et al. (1988) Requests for reprints should be addressed to: reported a similar phenomenon occurring with arginine. Apart from Prof. Dr. E. A. van der Veen demonstrating the presence of releasable GH, these findings suggest a non-GRF dependent mechanism for these stimuli, probably operating Department of Endocrinology by inhibition of somatostatin. Whereas Shibasaki et al. (1985) argues Free University Hospital that somatostatin might be inhibited by the raise in catecholamine Postbus 7057 levels induced by hypoglycemia, according to other investigators hy1007 MB Amsterdam (Holland)
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398
Growth Hormone Release After the Sequential Use of Growth Hormone Releasing Factor and Exercise J. H. de Vries, R. J. P. Noorda, G. A. Voetberg and E. A. van der Veen Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands
Introduction
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Growth hormone (GH) secretion is under dual control of Growth Hormone Releasing Factor (GRF) and somatostatin. Whereas low or even non-detectable values are physiological in at random blood samples of normal individuals, several stimuli are used to evaluate the pituitary capacity to secrete GH: insulin-hypoglycemia, arginine, L-DOPA, sleep, exercise and GRF. Since an absent response to one stimulus does not exclude response to another, it is recommended to perform at least two tests when evaluating pituitary reserve (Davies and Johnston 1987). All stimuli but sleep, exercise and GRF are unpleasant to the subject tested. The sleeptest is difficult to perform in an outpatient setting. To determine whether the GRF and exercise stimulus influence each other when performed shortly after each other, we measured Growth Hormone response to a bolus of GRF followed by exercise and vice versa. Subjects and Methods Subjects studied were five healthy young men, mean age 24 (range 22 to 29) years. They were within 15 % limits of normal body weight, used no medication and a normal diet. Informed consent was obtained in advance of the study. After an overnight fast an i. v. cannula was inserted. After 30 minutes rest (t = 0) a bolus of 100 u,g of human pancreatic growth hormone releasing factor 1-44 (hpGRF 1-44) (Somatobiss, Bissendorf Peptide) was administered. Blood samples for the determination of GH were drawn at t = - 15, 0, 10, 20, 30, 40, 50, 60 and 70 minutes. On t = 170 the subjects started exercising for 20 minutes on a bicycle ergometer against a load of 100 W. Blood samples were drawn at t = 150, 170, 180, 185, 190, 200 and 205 minutes (testsequence 1). Two weeks later testing was repeated in reversed sequence (testsequence 2). Exercise was performed for 20 minutes, two hours later (t= 140) the bolus of GRF was administered. Blood samples were drawn at t = - 15, 0, 10, 15,20, 25, 30, 35, 125, 140,150,160,170,180, 190,200 and 210 minutes. GH levels were determined by radioimmunoassay (Oris, France). The lowest detectable level of this assay is 0.5 ng/ml. The intra- and interassay coefficients of variation are 8.2% and 11.9% respectively. For statistical analysis Student's t-test for paired data was used.
Fig. 1 Top: Serum GH (ng/ml, mean + SEM) after 100 ug GRF i. v. followed by 20 minutes exercise (n = 5), Bottom: Serum GH (ng/ml, mean + SEM) during 20 minutes exercise followed by 100 ug GRF i.v. (n = 5).
Results Results of the first testsequence are depicted in Figure 1 (top). Mean basal level was 1.0 ng/ml (SEM 0.2). All subjects responded to the bolus of GRF, mean peak value being 24.6 ng/ml (SEM 6.8). The GH response to exercise after prior administration of GRF is absent. When performed in reversed order, the results are as
given in Figure 1 (bottom). All subjects reacted with a GH response to exercise, mean peak value response being 3.7 ng/ml (SEM 1.1). All subjects responded to subsequent injection of a bolus of GRF, but the mean response was lower than after GRF administration alone: 17.1 ng/ml (SEM 9.3) vs 24.6 ng/ml (p < 0.05).
Horm.metabol. Res. 23 (1991)397-398 © Georg Thieme Verlag Stuttgart • New York
Received: 24 July 1990
Accepted: 11 March 1991 after revision
Horm. metab. Res. 23 (1991)
J. H. de Bries, R.J. P. Noorda, G. A. Voetberg andE. A. van der Veen
Discussion This study shows that prior injection of a bolus of GRF abolishes the GH response to exercise and exercise attenuates the GH response to subsequent administration of abolus of GRF.
poglycemia directly inhibits somatostatin (Page, Koppeschaar, Edwards, Dieguez and Scanlon 1987). Our findings of an abolished response to exercise after GRF pretreatment do not support the hypothesized role of catecholamines in the inhibition of somatostatin.
Different mechanisms for the stimuli mentioned above probably explain why in a given subject the absence of GH reThat the subsequent administration of various lease to one stimulus does not exclude a response to another. Although stimuli influences GH response is reported several times. Four studies GRF and exercise are both stimuli that do not endanger, nor put excesshowed no or a distinctly diminished GH response following a second sive strain on the subject tested, it is probably better to use both a non bolus of GRF given shortly after a first one, a phenomenon ascribed to GRF dependent and a GRF dependent stimulus when evaluating desensitization of the somatotrophes or to a reactive somatostatin release in the portal circulation after the first bolus of GFR (Losa, Bock, pituitary reserve. Schopohl, Stalla, Muller and von Werder 1984; Shibasaki, Hotta, Masuda, Imaki, Obara, Demura, Ling and Shizume 1985; Sartorio, References Spada, Bochicchio, Atterrato, Morabito and Faglia 1986; Page, Dieguez, Valcavi, Edwards, Hall and Scanlon 1988). After pretreat- Davies,R.R.,D. G. Johnston:!. Roy. S. Med. 80:3-5 (1987) ment with GRF, Page et al. (1988) also found an abolished GH re- Losa, M., L. Bock, J. Schopohl, G. K. Stalla, 0. A. Muller, K. von Wersponse to L-DOPA, suggesting an endogenous GFR dependent mechrferActa Endocrinol. 107:462-470(1984) anism for L-DOPA: after desensitization of the somatotrophes by exo- Page, M. D., H P. E. Koppeschaar, C. A. Edwards, C. Dieguez, M. F. genous GRF the subsequent endogenous GRF rise induced by LScanlon:Clin. Endocrinol. 26: 589-595 (1987) DOPA does not result in GH release. Our findings with exercise as a Page, M. D., C. Dieguez, C. Valcavi, C. Edwards, R. Hall, M. F. Scansecond stimulus are similar, suggesting an endogenous GFR dependlon:C\in. Endocrinol. 28:551-558 (1988) ent mechanism for GH release after exercise as well. The significantly Sartorio, A., A. Spada, D. Bochicchio, A. Atterrato, F. Morabito, G. Falower GH response to GRF after prior exercise can be explained by glia.-Neuroendocr. 44:470-474 (1986) partial desensitization of the somatotrophes after the relative weak Shibasaki, T., M. Hotta, A. Masuda, T. Imaki, N. Obara, H. Demura, stimulus exercise or by a milder somatostatin release respectively. N. Ling, K. Shizume:J. Clin. Endocrinol. Metab. 60: 1265-1267 Another potential explanation for the observed lower GH secretion (1985) after a second stimulus is exhaustion of the somatotrophe. However, Shibasaki et al. (1985) found an enhanced GH response to insulin hypoglycemia after prior administration of GRF and Page et al. (1988) Requests for reprints should be addressed to: reported a similar phenomenon occurring with arginine. Apart from Prof. Dr. E. A. van der Veen demonstrating the presence of releasable GH, these findings suggest a non-GRF dependent mechanism for these stimuli, probably operating Department of Endocrinology by inhibition of somatostatin. Whereas Shibasaki et al. (1985) argues Free University Hospital that somatostatin might be inhibited by the raise in catecholamine Postbus 7057 levels induced by hypoglycemia, according to other investigators hy1007 MB Amsterdam (Holland)
Downloaded by: Universite de Sherbrooke. Copyrighted material.
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