Growth phases

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.


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).


In children, pulsatile LH release can be detected using highly sensitive modern hormone assay systems and mathematical techniques to properly identify pulsatile patterns of secretion (30-37). However, pulses are of very small amplitude and slow frequency. The onset of
pubertal maturation is heralded by the development of a diurnal pattern of LH secretion (Figure 2, left panels).


Nocturnal augmentation of gonadotrophin release marks the onset of sexual development. The mechanism(s) underlying disinhibition of LH secretion is uncertain, but likely reflects input
from higher CNS centers. Clearly, enhanced secretion of GnRH is
needed as blockade of GnRH action can abolish the nocturnal release of LH and secretagogues for GnRH can induce LH release (37). The increases in circulating LH concentration reflect both an augmentation of pulse amplitude and, to a lesser degree, pulse frequency during the earlier phases of the normal sleep cycle. Through pubertal maturation, wake-time LH pulses become more prominent and an array of mathematical parameters measuring LH release increase (35). With the rise in gonadotrophins is an increase in gonadal steroid production and the development of secondary sexual characteristics. Enhanced secretion of testosterone and estradiol also initially follows an initial diurnal pattern with peak values lagging the gonadotrophin bursts. In females, pubertal maturation of hypothalamic/pituitary/ovarian axis results in the dynamic hormonal milieux of the menstrual cycle (see below). In the adult male, gonadotrophin levels are more stable with consistent amplitude and frequency (approximately every 90 minutes) of LH throughout a 24-hour period.



Figure 6. Pulsatility of circulating GH levels in adult men and women.


Exercise is a powerful stimulus to secretion of GH (253), which occurs by about 15 min from the start of exercise (254). The kinetics may vary between subjects, an effect which is likely to be related to differences in age, sex and body composition (255). Ten minutes of high-intensity exercise is required to stimulate a significant rise in GH (256). Anaerobic exercise causes a larger release of GH than aerobic exercise of the same duration (257). Acetylcholine, adrenaline, noradrenaline and endogenous opioids have been implicated in exercise-induced GH release (200). However, ghrelin levels do not rise in acute exercise, indicating that ghrelin may not have a role to play in exercise-induced GH release (258).


Insulin-induced hypoglycaemia is another powerful stimulus to GH secretion (Figure 7) (259, 260). The peak GH levels achieved during insulin stress testing correlate well with those achieved during slow wave sleep (261). The hypoglycaemic response is mediated by a2-adrenergic receptors (262) to cause inhibition of somatostatin release (200), although other evidence argues for a role of stimulated GHRH release, as a GHRH receptor antagonist significantly suppressed hypoglycaemic GH release (263). Ghrelin is unlikely to be involved in the GH respons
e to insulin-induced hypoglycaemia as ghrelin levels are suppressed by the insulin bolus (264).

Figure 7. Normal response of GH to insulin-induced hypoglycaemia (2.2 mmol/l). Peak GH secreted is 20 mU/l.



In contrast to hypoglycaemia, ingestion of an oral glucose load causes an initial suppression of plasma GH levels for 1-3 hours

(Figure 8), followed by a rise in GH concentrations at 3-5 hours
(267). The initial suppression could be mediated by increased somatostatin release as pyridostigmine, a postulated inhibitor of somatostatin release, blocks this suppression (268). Circulating ghrelin levels also fall following ingestion of glucose (269). The GH response to ghrelin and GHRH infusions is blunted by oral glucose, an effect that is probably mediated by somatostatin (270). The later rise in GH levels is postulated to be due to a decline in somatostatinergic tone plus a reciprocal increase in GHRH, leading to a  rebound rise (200).

Figure 8. GH response to 75g oral glucose in 8 non-acromegalic, non-diabetic women, given at time 0. Error bars denote SD. Note the high variability of the baseline GH level due to the pulsatile nature of GH secretion. GH levels fall to <0.5 mU/l at 120 minutes.


In type I diabetes mellitus, GH dynamics are disordered, with elevated 24 hour release of GH (271). Deconvolution analysis shows that GH pulse frequencies and maximal amplitudes are increased. The latter is accounted for by higher

alley levels (272). Better glycaemic control appears to normalize these disordered dynamics (273). The pathophysiological mechanism appears to involve reduced somatostatinergic tone (200).

There is conflicting evidence for increased, decreased or normal GH dynamics in type II diabetics. It is likely that this reflects two factors acting in opposite directions: (1) the confounding factor of obesity in these patients, which leads to hyposecretion of GH; and (2) the hyperglycaemia, which leads to hypersecretion (200).

Hormone table and MA

GH = Secretion regulated by GHRH and somatostatin.

Secretion is pulsatile and increased by sleep, stress, puberty hormones, starvation, exercise, and hypoglycemia


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