Given responsive somatotropes and adequately releasable GH pools within the anterior pituitary gland, analysis of the discrete secretory pulses of GH provides information about the frequency and amplitude of serum hormone concentration peaks. It gives insight into the neuroendocrine mechanisms that control both ultradian and circadian rhythms of pituitary hormone release (14). There is individual variability in GH concentration pulses in blood as discrete peaks but using new methodologies for GH analysis it has been possible to estimate the underlying hormone secretion rates from serial GH measurements and calculate the half- life of endogenous hormone released into the circulation. (80-82).
These new analytical methodologies together with the establishment of ultra-sensitive GH assays made it possible to demonstrate gender differences in the regularity of GH secretory activity in human (81), with greater irregularity in females compared to males (82).
Within the first hours of postnatal life in the human markedly amplified GH secretory bursts are observed throughout day and night (83). Premature infants also exhibit marked GH secretion and reduced plasma IGF-I levels. Such amplified GH response may be due to relatively low IGF-I levels.
Extensive literature exists on the pattern of GH secretion in puberty but only in the last decade studies have concentrated in the prepubertal period. In the decade before puberty 24h pulsatile GH secretion rates (estimated as 200-600ug/day) are stable from day to day and approximate (84-86).
The onset of clinical and biochemical manifestations of puberty in boys and girls is associated with a marked increase in GH pulse amplitude and mass without changes in pulse frequency or changes in GH half-life (44-46; 87, 88). Studies in which either oestrogen or testosterone treatment have been selectively used have shown that both cause an increase in GH released per secretory bursts. Thus, this is likely to represent the underlying neuroendocrine mechanism causing the increased GH secretion observed in puberty (44-46). This increased physiological GH secretion is associated with a significant increase in IGF-I and IGFBP-3 serum concentrations possibly all driven by sex steroid hormones.
It has been postulated that this unusual event of concomitant rise in GH and IGF-I could be due to changes in central hypothalamus-pituitary and in auto-feedback sensitivity.
Human growth is a rather regular process characterized by a pattern of changing growth rate or height velocity from infancy to adulthood (Figure 2, 89). In the short-term the height velocity of a healthy individual fluctuates i.e. seasonal or longer periodicity has been shown (90-92). It appears that some phases of growth are more important in their effect on final height. For example a child who is born short has a greater chance of being a short adult. The timing and duration of puberty are also crucial factors in determining final height.
Figure 2. Growth in height of the Montebeillard.s son from birth to 18 years first described by Scanmon in 1927. Top panel: height attained at each age. Bottom panel: Growth velocity. Reproduced with permission from Tanner JM (89).
The infancy-childhood-puberty growth model divides the human growth process into three phases (89). Thus, the infancy phase begins in the middle of gestation and tails off at around 4 years of age, possibly representing the postnatal continuation of fetal growth. The childhood phase starts during the second half of the first postnatal year slowly decelerating and leading into the final phase at puberty. The puberty phase represents additional growth beyond the childhood phase with significant acceleration until the age of peak height velocity followed by a deceleration until linear growth finally ceases (Figure 3, 89).
The dynamic process underlying in the growth phases are under the control of complex regulatory mechanisms. The tendency to maintain a tight path in the growth channel and a prerequisite of catch-up growth was called "canalization" by Waddington while referring to the growth pattern of small animals and later adapted by Tanner in the context of human linear growth (89).
In 1963, Prader et al described the phenomenon of catch-up growth observed in children after chronic illness or in those who suffered from starvation (93, 78). For reviews, the reader is referred to references and the article by Wit and Boersma (78) Catch-up growth is the phenomenon by which rapid growth occur after a period of illness or malnutrition allowing a child to return to the growth curve he/she had before the illness. Complete catch-up growth leads to a normal final height but incomplete catch-up growth will result in a compromised final height (78)
The mechanisms underlying this important biological event still remain unclear. Tanner proposed the existence of a "time tally" a central regulatory mechanism that senses the organism's height via a "humoral factor" (90) and which could be involved in the catch-up phenomenon. Mosier referred to it as "the age-appropriate set point for body size" (94).
Although the mechanisms regulating catch-up growth remains unclear recent animal studies suggest a cross talk between central and peripheral mechanisms (78, 93) Therefore, some extrapolation from these studies appear reasonable.