J Clin Endocrinol Metab 40: 736, 1975
SOMATOMEDIN ACTIVITY IN CEREBROSPINAL FLUID
ABSTRACT. Somatomedin activity has been demonstrated in the cerebrospinal fluid (CSF) of 12 normal subjects and one patient with acromegaly. In all cases the concentration was lower in the CSF than in the corresponding serum, and a significant correlation was demonstrated between the somatomedin activity in the two body fluids (p < 0 . 0 1 ) . Human growth hormone has been measured in the cerebrospinal fluid (CSF) of both normal and acromegalic subjects (1). Many of the actions of this hormone are mediated by somatomedin (2) and it has been speculated that this peptide may play a key role in the feedback mechanisms controlling growth hormone secretion (3). The presence of somatomedin in CSF has not been described, and therefore CSF somatomedin activity has been measured and related to the corresponding serum levels. MATERIALS AND METHODS CSF was collected by lumbar puncture performed on 12 patients (8 males and 4 females) during the routine investigation of possible neurological disease. The mean age was 39 years (range 21-70 years). In each case the CSF was biochemically and cytologically normal. In addition, CSF was obtained from a 28 year old male with proven acromegaly during pneumoencephalography. This patient had suprasellar extension of the pituitary tumour. ^At the same time as the CSF collection venous blood was obtained in all cases. The CSF and sera were stored at -20°C until assayed. Somatomedin was bioassayed in both serum and CSF by the porcine cartilage technique of Van den Brande (4), using the incorporation of ^ 0 4 i n t o costal cartilage of freshly slaughtered animals weighing between 30 and 40 kg. A pool of 3 normal adult human sera served as the reference standard for the symmetrical 8 or 10 point assays with sample concentrations between 2.5% and Serum and CSF pairs from the same
subject were assayed simultaneously. Results were computed as potency ratios (reference standard equivalent to 1.00) from the calculated sulfate uptakes. To demonstrate qualitative similarity between the dose-response lines of the serum and CSF pairs, parallelism for each pair was computed (5). Serum and CSF inorganic sulfate concentrations were measured by a benzidin sulfate colorimetric method (6). The relationship between the normal individual CSF and serum concentrations was demonstrated by analysis of varianc RESULTS The mean serum somatomedin in the 12 subjects was 0.71 (range 0.36 - 1.09), falling into the previously determined normal range for adult sera in this laboratory (0.35-1.20; n = 27). Sera from four patients with hypopituitarism had values between 0.18 and 0.31. The mean CSF somatomedin was 0.28 (range O.i -0.40) and the mean CSF : serum ratio w< 0.39 (range 0 . 2 1 - 0 . 5 9 ) . The mean ind of precision for the standard reference serum was 0.10 (range 0.08 - 0.13; n = : and 0.17 for the samples (range 0.08 0.35; n = 26). The mean normal serum sulfate concen tration was 2.52 mg per 100 ml (jf 0.39 SD) and the mean CSF sulfate concentration was 0.67 mg per 100 ml (;f 0.12 SD) Analysis of variance showed a significant linear relationship between the serum and CSF values ( p < 0.01) for the 12 normal subjects (Fig. 1 ) . 736
Downloaded from https://academic.oup.com/jcem/article-abstract/40/4/736/2685051 by Leiden University / LUMC user on 16 January 2019
George R. Beaton, Julius Sagel and Larry A. Distiller Department of Physiology and Endocrine Division, Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
RAPID COMMUNICATIONS
737
Linfoot, J.A., J.F. Garcia, W. Wei, R. Fink, R. Sarin, J.L. Born, and J.H. Lawrence, J Clin Endocrinol Metab 31: 230, 1970. DaughaHay, W.H., K. Hall, M.S. Raben, W.D. Salmon, J.L. Van den Brande, and J.J. Van Wyk, Nature 235: 107, 1972. TarTner, J . M . , Nature 237^: 4 3 3 , 1972. Van den Brande, J.L., and M.V.L. Du Caju, Acta Endocrinol (Kbh) 7j5: 233, 1974. Figure I. Correlation between the serum and CSF somatomedin potency ratios Finney, D.J., Statistical Method in in the 12 normal subjects. The open Biological Assay, 2nd Ed., Chapter 4 circle represents the acromegalic Griffin, London, 1964. patient. Kleeman, C.R., E. Taborsky, and FH. Epstein, Proc Soc Exp Biol Med 91 DISCUSSION 480, 1956. McConaghey, P., and C.B. Sledge, We have demonstrated the presence Nature 225: 1249, 1970. of somatomedin activity in the CSF. In McConagTiey, P., and J. Dehnel, J all instances, the concentration in the 587, 1972. Endocrinol CSF was lower than that in the corres- 9. Hall, K., A. Holmgren, and U. Linponding serum. This finding, together dahl, Biochim biophys Acta 201: with the significant correlation 398, 1970. between the levels in the two body fluids, suggests that this peptide ACKNOWLEDGEMENT may cross the blood-brain barrier into the CSF. This is compatible with the This work was supported by the South current evidence that the sites of African Medical Research Council and the somatomedin production are the liver University of the Witwatersrand. (7), kidney (8) and possibly muscle (9). The possibility of somatomedin production in the central nervous system is not excluded. 05-
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SOMATOMEDIN ACTIVITY IN CEREBROSPINAL FLUID
ABSTRACT. Somatomedin activity has been demonstrated in the cerebrospinal fluid (CSF) of 12 normal subjects and one patient with acromegaly. In all cases the concentration was lower in the CSF than in the corresponding serum, and a significant correlation was demonstrated between the somatomedin activity in the two body fluids (p < 0 . 0 1 ) . Human growth hormone has been measured in the cerebrospinal fluid (CSF) of both normal and acromegalic subjects (1). Many of the actions of this hormone are mediated by somatomedin (2) and it has been speculated that this peptide may play a key role in the feedback mechanisms controlling growth hormone secretion (3). The presence of somatomedin in CSF has not been described, and therefore CSF somatomedin activity has been measured and related to the corresponding serum levels. MATERIALS AND METHODS CSF was collected by lumbar puncture performed on 12 patients (8 males and 4 females) during the routine investigation of possible neurological disease. The mean age was 39 years (range 21-70 years). In each case the CSF was biochemically and cytologically normal. In addition, CSF was obtained from a 28 year old male with proven acromegaly during pneumoencephalography. This patient had suprasellar extension of the pituitary tumour. ^At the same time as the CSF collection venous blood was obtained in all cases. The CSF and sera were stored at -20°C until assayed. Somatomedin was bioassayed in both serum and CSF by the porcine cartilage technique of Van den Brande (4), using the incorporation of ^ 0 4 i n t o costal cartilage of freshly slaughtered animals weighing between 30 and 40 kg. A pool of 3 normal adult human sera served as the reference standard for the symmetrical 8 or 10 point assays with sample concentrations between 2.5% and Serum and CSF pairs from the same
subject were assayed simultaneously. Results were computed as potency ratios (reference standard equivalent to 1.00) from the calculated sulfate uptakes. To demonstrate qualitative similarity between the dose-response lines of the serum and CSF pairs, parallelism for each pair was computed (5). Serum and CSF inorganic sulfate concentrations were measured by a benzidin sulfate colorimetric method (6). The relationship between the normal individual CSF and serum concentrations was demonstrated by analysis of varianc RESULTS The mean serum somatomedin in the 12 subjects was 0.71 (range 0.36 - 1.09), falling into the previously determined normal range for adult sera in this laboratory (0.35-1.20; n = 27). Sera from four patients with hypopituitarism had values between 0.18 and 0.31. The mean CSF somatomedin was 0.28 (range O.i -0.40) and the mean CSF : serum ratio w< 0.39 (range 0 . 2 1 - 0 . 5 9 ) . The mean ind of precision for the standard reference serum was 0.10 (range 0.08 - 0.13; n = : and 0.17 for the samples (range 0.08 0.35; n = 26). The mean normal serum sulfate concen tration was 2.52 mg per 100 ml (jf 0.39 SD) and the mean CSF sulfate concentration was 0.67 mg per 100 ml (;f 0.12 SD) Analysis of variance showed a significant linear relationship between the serum and CSF values ( p < 0.01) for the 12 normal subjects (Fig. 1 ) . 736
Downloaded from https://academic.oup.com/jcem/article-abstract/40/4/736/2685051 by Leiden University / LUMC user on 16 January 2019
George R. Beaton, Julius Sagel and Larry A. Distiller Department of Physiology and Endocrine Division, Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
RAPID COMMUNICATIONS
737
Linfoot, J.A., J.F. Garcia, W. Wei, R. Fink, R. Sarin, J.L. Born, and J.H. Lawrence, J Clin Endocrinol Metab 31: 230, 1970. DaughaHay, W.H., K. Hall, M.S. Raben, W.D. Salmon, J.L. Van den Brande, and J.J. Van Wyk, Nature 235: 107, 1972. TarTner, J . M . , Nature 237^: 4 3 3 , 1972. Van den Brande, J.L., and M.V.L. Du Caju, Acta Endocrinol (Kbh) 7j5: 233, 1974. Figure I. Correlation between the serum and CSF somatomedin potency ratios Finney, D.J., Statistical Method in in the 12 normal subjects. The open Biological Assay, 2nd Ed., Chapter 4 circle represents the acromegalic Griffin, London, 1964. patient. Kleeman, C.R., E. Taborsky, and FH. Epstein, Proc Soc Exp Biol Med 91 DISCUSSION 480, 1956. McConaghey, P., and C.B. Sledge, We have demonstrated the presence Nature 225: 1249, 1970. of somatomedin activity in the CSF. In McConagTiey, P., and J. Dehnel, J all instances, the concentration in the 587, 1972. Endocrinol CSF was lower than that in the corres- 9. Hall, K., A. Holmgren, and U. Linponding serum. This finding, together dahl, Biochim biophys Acta 201: with the significant correlation 398, 1970. between the levels in the two body fluids, suggests that this peptide ACKNOWLEDGEMENT may cross the blood-brain barrier into the CSF. This is compatible with the This work was supported by the South current evidence that the sites of African Medical Research Council and the somatomedin production are the liver University of the Witwatersrand. (7), kidney (8) and possibly muscle (9). The possibility of somatomedin production in the central nervous system is not excluded. 05-
0
025'
#
.
#
* * •
r = 08l
p
