FIGURE 6 Effects of human growth hormone (hGH) treatment on nitrogen, sodium, potassium, and phosphorus balances in an 11.5-year-old girl with pituitary dwarfism. Changes above the control baseline represent retention of the substance; below the line, they represent loss. (From Hutchings JJ, Escamilla RF, Deamer WC and Li, CH, J Clin Endocrinol Metab 1959; 19:759-764. With permission.)
44. Hormone Control of Growth
Growth is a slow, continuous process that takes place over more than a decade. It might be expected, therefore, that concentrations of GH in blood would be fairly static. In contrast to such expectations, however, frequent measurements of GH concentrations in blood plasma throughout the day reveal wide fluctuations indicative of multiple episodes of secretion rate. Because metabolism of GH is thought to be invariant, changes in plasma concentration imply changes in secretion. In male rats, GH is secreted in regular pulses every 3.0 to 3.5 hours in what has been called an ultradian rhythm. In humans, GH secretion is also pulsatile, but the pattern of changes in blood concentrations is usually less obvious than in rats. Frequent bursts of secretion occur throughout the day, with the largest being associated with the early hours of sleep (Fig. 7). In addition, stressful changes in the internal and external environment can produce brief episodes of hormone secretion. Little information or diagnostic insight, therefore, can be obtained from a single random measurement of the GH concentration in blood. Because secretory episodes last only a short while, multiple, frequent measurements are necessary to evaluate functional status or to relate GH secretion to physiological events. Alternatively, it is possible to withdraw small amounts of blood continuously over the course of a day and, by measuring GH in the pooled sample, to obtain a 24-hr integrated concentration of GH in blood.
The possible physiological significance of intermittent as compared with constant secretion of GH has received much attention experimentally. Pulsatile administration of GH to hypophysectomized rats is more effective in stimulating growth than continuous infusion of the same daily dose. However, similar findings have not been made in human subjects, whose rate of growth, like that of experimental animals, can be restored to normal or near normal with single daily or every other day injections of GH. While expression of some hepatic genes appears to be sensitive to the pattern of changes in plasma GH concentrations in rodents, there is neither evidence for comparable effects in humans nor an obvious relationship of the affected genes to growth of rodents. In normal human adults, the same amount of GH given either as a constant infusion or in eight equally spaced brief infusions over 24 hours increased IGF-I and IGFBP-3 to the same extent.
Using the continuous sampling method, it was found that GH secretion, though most active during the adolescent growth spurt, persists throughout life long after the epiphyses have fused and growth has stopped (Fig. 8). In mid-adolescence the pituitary secretes between 1 and 2 mg of GH per day. Between ages 20 and 40 years, the daily rate of secretion gradually decreases in both men and women, but remarkably, even during middle age, the pituitary continues to secrete about 0.1 mg of GH every day. Low rates of GH secretion in the elderly may be related to loss of lean body mass in later life. Changes in GH secretion with age primarily reflect changes in the magnitude of secretory pulses.
In addition to spontaneous pulses, secretory episodes are induced by such metabolic signals as a rapid fall in blood glucose concentration or an increase in certain amino acids, particularly arginine and leucine. The
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