Growth in prepubertal children - short term changes and endocrine regulation. The one-year growth study

Abstract

Human growth is a dynamic process characterized by accelerations and decelerations. The hypothalamus directs longitudinal growth, through the pulsatile secretion of growth hormone (GH) from the pituitary. GH induces differentiation of epiphyseal cells in the growth plate of long bones and stimulates the autocrine and paracrine action of insulin-like growth factor I (IGF-I). Local IGF-I stimulation increases cell numbers and volumes. It is not known if the dynamic short-term growth changes are related to changes in endocrine regulation. Improved methods for non-invasive measurement of short-term growth provide tools to study growth in parallel with markers of its endocrine regulation.The general aims of the study was to investigate changes in short-term growth, to explore short-term changes in the GH-IGF-I axis, and to elucidate if any such variations show a time correlation.Healthy prepubertal children were followed longitudinally. In a pilot study, measurements of the lower leg length (LLL) with knemometry were evaluated in 50 children. Since it was found that short-term growth in LLL could be measured accurately with knemometry over 1-month interval, while height demands 3-months interval, the main study was undertaken with monthly follow-up intervals. In the main study, growth was followed in 84 children, together with urinary GH and serum measurements of GH-binding protein (GHBP), IGF-I, IGF-binding protein-3 (IGFBP-3) and leptin, the hormone related to fat cells.Monthly variations were found, not only in growth, but also in growth factors involved in the GH-IGF-I axis as well as in leptin. Serum concentrations of GHBP, IGF-I, IGFBP-3 and leptin could be doubled, or reduced by half, when samples was taken with 1 month interval. An even larger variation was found in urinary GH excretion, which could be reduced when excretion values were adjusted for the influence of urine volume.Besides monthly changes, seasonal variation exists for growth in LLL, with a similar pattern, but larger amplitude, than for height. An opposite monthly pattern was found for GHBP. Indication that changes in IGF-I and IGFBP-3 are related to season was also found, since such changes correlate to changes in outdoor temperature.The monthly variation in longitudinal growth was only correlated to changes in IGF-I and IGFBP-3. Instead, weight changes correlated to changes in GHBP, leptin and urinary GH as well as IGF-I and IGFBP-3, while intermittent illness influenced measurements of GHBP and IGF-I but not IGFBP-3. Changes in serum concentrations of IGF-I and IGFBP-3 are closely related, although they provide different information. IGF-I gives strongest information about influences during the previous month and IGFBP-3 during the last three months. The finding that measurements of GH in urine did not correlate to growth, IGF-I or IGFBP-3, but to urine volume, and in addition, that serum GHBP correlate inversely with urinary GH suggest that renal factors affects the fraction of GH excreted in the urine.Despite the large monthly variations, the individual annual mean serum concentrations of GHBP, IGF-I, IGFBP-3 and leptin were related to the size of the child, either as height or as weight.In conclusion, monthly measurements reveals dynamic changes not only in growth, but also in urinary GH, serum GHBP, IGF-I, IGFBP-3 and leptin. Correlation in time between these changes indicate that changes have biological significance.