Circulating GH levels in man fluctuate widely due to pulsatile GH secretion by the pituitary gland. During much of the time, plasma GH is undetectable by current assays. This is punctuated by occasional secretory episodes, resulting in plasma GH peaks of varying height. The principal diurnal secretory event for GH is that associated with early slow wave sleep, but little is known about the prevailing level and dynamics of GH during the day. We used a new ultrasensitive immunoradiometric assay for GH (Boots-Celltech IRMA; limit of detection, 20 ng/L) to measure plasma GH in the previously undetectable range and to assess its diurnal pattern. Plasma GH was measured every 20 min over a 24-h period in 12 normal subjects (6 men and 6 women, aged 20-47 yr) under physiological conditions. Time series analysis of plasma GH patterns was performed by the Cluster algorithm, autocorrelation, and spectral analysis. Plasma GH, as measured by IRMA, was detectable at all time points and ranged from 40-19,695 ng/L. Dynamic fluctuations occurred within and above the previously undetectable range, with amplitudes varying over 3 orders of magnitude. Women had significantly higher overall GH levels, higher peak amplitudes, and higher valley levels/nadirs than men. GH pulses occurred with an average frequency of about 13/day in both sexes, with a dominant, but not strictly periodic, 2-h rhythmicity. We conclude that in man pulsatile GH secretion occurs throughout the day, and that it is oscillatory rather than episodic. This neurosecretory pattern has eluded recognition heretofore because of the lack of assay sensitivity. Women of reproductive age have higher pulse amplitudes and a higher baseline but equal pulse frequency compared to men. Previous estimates of integrated GH concentrations and GH production rates were too high by a factor of 2 due to overestimation of GH levels in the undetectable range.

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The identification of specific GH-binding proteins (GH-BP) in human plasma, one of which is a fragment of the GH receptor, has added new complexity to the state of GH in the circulation. A major proportion of GH circulates in complexed form, which differs in kinetics and possibly bioactivity from free GH. Little is known about the regulation of the GH-BP, their constancy or variation in plasma, or plasma factors affecting GH binding. Consequently, the temporal pattern of bound and free GH in plasma is also unknown. Knowledge about possible spontaneous variability in GH-BP levels/activity is required for physiological investigations and comparative studies among different populations. To address these issues, we measured GH-binding activity in plasma every hour over a 24-h period in six normal adults (three men and three women). A standardized GH binding assay, employing incubation of plasma with [125I]GH and separation of bound from free GH by gel filtration, was used. GH-BP activity showed no significant diurnal variation in any subject. The average GH-BP activity was similar in all subjects, although statistically significant differences were found between some subjects. No age- or sex-related differences were identified. We conclude that in normal man plasma GH-BP activity is constant throughout the day, thereby implying 1) constancy of binding protein (and possibly GH receptor) concentration, and 2) absence of significant fluctuations in potential binding inhibitors/enhancers in plasma.

The assessment of growth hormone (GH) secretory status is often difficult because of the intermittent nature of GH release and resulting wide swings in plasma GH levels. Urinary GH excretion holds promise as an index of integrated plasma GH free of this limitation, but technical problems have prevented its use until recently. We adapted a recently developed method for accurately measuring GH and its various molecular forms in urine to the determination of GH excretion rates. The method involves diafiltration and immunoextraction of GH from urine, with monitoring of recovery and final quantification by radioimmunoassay. Twenty-four h GH excretion rates were determined in 30 normal adults (15 men and 15 women) and 4 acromegalic patients. They ranged from 1 to 81 ng/24 h in men, from 1 to 70 ng/24 h in women and from 87 to 1660 ng/24 h in acromegaly (medians = 8.7, 18.0 and 267 ng/24 h, respectively). Excretion rates varied widely, not only between subjects, but also within the same subject on different days. Women and younger subjects tended to excrete more GH than men and older subjects, although these trends were not statistically significant. Acromegalics excreted significantly more GH than normals (p less than 0.001). Twelve normal subjects underwent simultaneous assessment of 24 h integrated plasma GH (sampling every 20 min) and urine GH excretion. Urine GH correlated weakly (r = 0.45) with integrated plasma GH.(ABSTRACT TRUNCATED AT 250 WORDS)