GH stimulates IGF-I production by the liver, which in turn inhibits GH synthesis and secretion by the pituitary and hypothalamus in a "long feedback" loop. GH also exerts negative feedback on the release of GHRH through a "short feedback" loop and increases somatostatin release (Fig. 41.17). 

The secretion of GH follows a diurnal rhythm, with peak secretion occurring in the early morning during deep slow-wave sleep. GH secretion is lowest during the day and is influenced by sleep-wakefulness patterns rather than light-dark patterns. Individuals who work night shifts experience a phase shift in their GH secretion rhythm. GH is secreted in a pulsatile manner, leading to wide variations in serum GH levels (ranging from 0 to 30 ng/mL, with most values falling between 0 and 3). However, measuring serum GH levels has limited clinical utility due to this variability and the heterogeneity of circulating GH. Instead, IGF-I secretion, regulated by GH and possessing a longer half-life, can be used to assess the status of the GH axis, particularly in young patients.

GH secretion is regulated differently depending on the physiological state. It is considered a "stress hormone" and is increased by neurogenic and physical stress. GH promotes lipolysis, enhances protein synthesis, and opposes the blood glucose-lowering effects of insulin. Acute hypoglycemia stimulates GH secretion, making GH a hyperglycemic hormone. Certain amino acids, such as arginine, can also stimulate GH secretion. Conversely, an increase in blood glucose or free fatty acids inhibits GH secretion. Obesity, characterized by insulin resistance and increased circulating free fatty acids, also inhibits GH secretion. On the other hand, exercise and starvation stimulate GH secretion.

The pattern of GH secretion throughout a lifetime is depicted in Fig. 41.18. GH secretion increases during the neonatal period when growth becomes dependent on GH and IGF-I. It remains high throughout childhood and peaks during puberty, particularly in the presence of estrogen (in females) and via aromatization in males. Thyroid hormone also enhances GH and IGF-I secretion to support bone growth and maturation. In adults, GH production continues to play a role in metabolism until levels decline during senescence.
Fig. 41.17). GH stimulates IGF-I pro duction by the liver, and IGF-I then inhibits GH synthesis and secretion by the pituitary and hypothalamus in a classic “long feedback” loop. In addition, GH itself exerts negative feedback on release of GHRH through a “short feedback” loop. GH also increases somatostatin release.
GH secretion, like ACTH, shows prominent diurnal rhythms, with peak secretion occurring in the early morning just before awakening. Its secretion is stimulated during deep slow-wave sleep (stages III and IV). GH secretion is lowest during the day. This rhythm is entrained to sleep-wakefulness patterns rather than light-dark patterns, so a phase shift occurs in people who work night shifts. As is typical of anterior pituitary hormones, GH secretion is pulsatile. Levels of GH in serum vary widely (0–30 ng/ mL, with most values usually falling between 0 and 3). Because of this marked variation and the heterogeneity of circulating GH, measurement of serum GH levels is of limited clinical utility. Since IGF-I secretion is regulated by GH and possesses a longer half-life that buffers pulsatile and diurnal changes in GH secretion, it may be used to assess the status of the GH axis, especially in young patients.
GH secretion is differentially regulated depending on the physiological state. GH is classified as one of the “stress hormones” and is increased by neurogenic and physical stress. It promotes lipolysis, increases protein synthesis, and antagonizes the ability of insulin to reduce blood glucose levels. It is not surprising, therefore, that acute hypoglycemia is a stimulus for GH secretion and GH is classified as a hyperglycemic hormone. A rise in the serum concentration of some amino acids also stimulates GH secretion; administration of arginine is used for provocative testing of GH secretion. In contrast, an increase in blood glucose or free fatty acids inhibits secretion of GH. Obesity also inhibits GH secretion, in part because of insulin resistance (relative hyperglycemia) and increased circulating free fatty acids. Conversely, exercise and starvation stimulate GH secretion.
The lifetime pattern of GH secretion is shown in
Fig.
41.18 . GH secretion increases in the neonatal period as growth becomes GH and IGF-I dependent. It remains high throughout childhood and peaks during puberty, when estrogen (in females and also males via aromatization) promotes even higher rates of GH secretion. Thyroid hormone also enhances GH and IGF-I secretion to support bone growth and maturation. Adults continue to produce GH, consistent with its role in metabolism, before levels fall during senescence.