Neuroendocrine and metabolic regulation of plasma growth hormone secretory profiles

Like many other neuroendocrine hormones, growth hormone (GH; somatotropin) secretion is pulsatile with regular releasing bursts on a relatively low constitutive basal secretion. This chapter discusses current knowledge of the regulation and the function of GH pulsatile profiles, with new development of laboratory approaches and introduces knowledge about GH functions on metabolic regulation in addition to the conventional concept of a role in regulating body growth. As reported in the literature, amplitude, frequency, and regularity of GH secretion are tightly linked to metabolic conditions with clear species and gender differences. In response to negative and positive energy balances, the GH pulsatile pattern changes to mobilize or store energy in adipose, muscle, and liver in order to accommodate the changing nutritional conditions. Changes in GH pulsatility are achieved through regulating the hypothalamo–pituitary GH axis with altered levels of key stimulatory and inhibitory hormones, GH-releasing hormone (GHRH) and somatostatin (SRIF, somatotropin release inhibiting factor). The hypothalamic–pituitary GH axis is constantly under the influence of peripheral metabolic factors, such as lipid and glucose levels; peripheral metabolic regulatory hormones, such as leptin and insulin; and central metabolic regulatory neuropeptides, such as neuropeptide Y and\ua0melanocortin. Regulation of the hypothalamic–pituitary GH axis is achieved through activation of cell membrane receptors, intracellular signaling pathways, and membrane ion channels. Detailed regulatory mechanisms are discussed in this chapter in order to understand the coupling of cell electrophysiological properties and the hormone secretory process of exocytosis in hypothalamic neurons and pituitary GH-secreting somatotrophs. Technical advances in electrophysiology, cell imaging analysis, and real-time in vivo hormone analysis are discussed to deepen the understanding of physiological and pathophysiological regulation of GH secretion. Future directions are also discussed, as are unanswered questions in this field