0021-972X/78/4705-1129$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society

Vol. 47, No. 5 Printed in U.S.A.

Brain Growth-Promoting Activity in Human Serum: Relationship to Growth Hormone and Somatomedin VICKI R. SARA, MARGARET C. STUART, R. RUTHERFORD, S. MOORE, AND L. LAZARUS Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, Australia ABSTRACT. Brain growth-promoting activity and somatomedin activity were assessed in serum collected from patients with pituitary disorders of GH secretion. Brain growth-promoting activity correlated with soma-

P

REVIOUS studies led us to propose that fetal brain growth was regulated by a GHdependent growth factor (1). Serum contained growth-promoting activity which stimulated fetal brain cell DNA synthesis in vitro (2). Serum levels of brain growth-promoting activity (BGA) were shown to be GH dependent in rats (2), but the identity of BGA and, particularly, its relationship to the isolated somatomedins remained unclear. The aim of the present preliminary study was to examine the relationship between somatomedin activity (SM) and BGA.

tomedin activity in serum, and both rose in response to GH administration. (JClin Endocrinol Metab 47': 1129, 1978)

and results were expressed as units per ml serum in relation to the reference serum, which was given a value of 1 U/ml. Serum GH was determined by RIA (4). Correlation analysis was performed between serum levels of BGA and SM, and significance was determined by t test (5).

Results

The relationship between BGA and SM is shown in Table 1. A highly significant correlation between these two measures was obtained (r = 0.91, t = 4.99, P < 0.005). Similar to SM, a significant difference in serum BGA was found between acromegalics and patients Materials and Methods with hypopituitarism (x ± SD; acromegalics, Single serum samples were collected from seven patients classified on the basis of both hormonal 1.56 ± 0.21; hypopituitarism, 0.77 ± 0.12; t = and clinical data (Table 1). Four patients had ac- 4.5432, P < 0.01). The patient receiving GH romegaly, of which one was hypophysectomized. therapy showed high serum levels of both Three were GH deficient, with one being on long BGA and SM in relation to the normal referterm therapy with GH. The response of BGA and ence serum. SM to GH administration was assessed in a further Figure 1 shows the effect of GH administrapatient. A 6.5-yr-old boy with short stature was tion on serum levels of BGA, SM, and GH in given two im injections of 5 mg human GH (hGH; the short stature child. The serum concentra1 U/mg) 72 h apart. Serum was collected before the tions of BGA and SM were low before GH first injection and after 4, 8, 24, 48, and 72 h when administration Increases in BGA and SM the second injection was given. Serum samples were were found in response to the first GH injecthen collected at 6 and 24 h. Serum BGA was assessed as described in detail tion; then, as serum GH levels declined, BGA previously (2). Serum SM was determined by the and SM also declined. A second GH injection weanling rat cartilage method (3). Both assays used again elicited a rise in serum BGA and SM. the same reference serum from normal adult males, Variation in the response of BGA and SM was observed. The highest serum BGA occurred 8 Received October 15, 1976. h after the first GH injection, whereas that for Address requests for reprints to: V. R. Sara, Department of Psychiatry, Karolinska Institute, St. Goran's Hos- SM occurred 48 h after hormone administration. No difference in response times of BGA pital, Box 12500, S-112 81 Stockholm, Sweden. 1129

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 09:26 For personal use only. No other uses without permission. . All rights reserved.

1130

and SM was noted after the second injection of GH, but samples were only collected at 6 and 24 h. More frequent sampling would be required to determine differences in response times. Discussion The present data demonstrate that BGA is responsive to GH in humans. Serum levels of BGA were reduced in GH deficiency or after hypophysectomy when compared to those associated with GH hypersecretion or after GH therapy. Responsiveness to GH was clearly demonstrated by the rapid rise of BGA after each of two GH injections to one patient. A very strong association between serum levels of BGA and SM was observed. This finding does not necessarily imply that BGA and SM are identical, for the high correlation coefficient may simply reflect the GH dependency of both substances. Preliminary data indicate that somatomedin B is not the brain trophin (6). Somatomedin A, somatomedin C, insulin-like growth factors 1 and 2 and multiplication stimulating activity are GH dependent (7) and others may be found so. If BGA proves to be a further function for one of these peptides, then specificity of action may simply be due to the differential sensitivity of tissues during development. On the other hand, if BGA represents a specific brain trophin, then the question of its role in adult brain function TABLE 1. Serum BGA and SM values in seven patient

Patient

Description

1 2 3 4

Acromegaly Acromegaly Acromegaly Hypophysectomized for acromegaly GH deficiency GH deficiency GH deficiency on long term GH therapy

5 6 7

-ICK&M • 1978 Vol47 • No S

COMMENTS

hGH (mU/liter) 17 560 37

Brain growth-promoting activity in human serum: relationship to growth hormone and somatomedin.

0021-972X/78/4705-1129$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society Vol. 47, No. 5 Printed in U...
221KB Sizes 0 Downloads 0 Views