Diurnal Rhythm of Growth Hormone-Independent Binding Protein for Insulin-like Growth Factors in Human Plasma*

Abstract

An antibody raised against the major insulin-like growth factor (IGF)-binding protein in amniotic fluid (BP-28) was used to measure the levels of a cross-reacting protein in human plasma by RIA. Plasma BP-28 immunoreactivity had an apparent mol wt of 35,000 by high performance permeation chromatography. Sampled hourly for 12- or 24-h periods in 15 children with a wide range of GH secretory activity, plasma BP-28 levels showed a marked diurnal cycle, rising 10- to 20-fold between 2400 and 0600 h to a peak of 50-500 micrograms/L, then falling to basal levels (0-40 micrograms/L) by 1200 h. Plasma GH levels were measured at 20-min intervals in the same subjects. Neither peak nor basal BP-28 levels were significantly associated with chronological age, bone age, mean or peak nocturnal GH secretion, relative height, or relative growth velocity in tall, normal, short, or GH-deficient children. Plasma proteins measured in a RIA for 53,000 mol wt GH-dependent IGF-binding protein (BP-53) did not vary diurnally. The IGF-binding activity of plasma BP-28, measured by incubating plasma with IGF tracer and precipitating the BP-28-IGF complex with anti-BP-28 antiserum, closely paralleled the morning rise in BP-28 immunoreactivity. Immunoprecipitable BP-28 bound both IGF-I and IGF-II tracers, with a clear preference for IGF-I, and unlabeled IGF-I was more effective than IGF-II in displacing either tracer IGF. We conclude that plasma BP-28 levels in children have a marked diurnal rhythm which is unrelated to GH secretory activity.