Effects of adult growth hormone deficiency and growth hormone replacement on circadian rhythmicity.

In health, growth hormone (GH) is secreted in a circadian rhythm with superimposed pulsatility. Temporal fluctuations of hormone concentrations are essential for physiological action, and loss of diurnal rhythm is important in the development of disease. GH feedback occurs through the hypothalamus and involves neuropeptides such as somatostatin, GH-releasing hormone, GH-releasing peptides and neuropeptide Y. In addition, the same neuropeptides are involved in the regulation of other hormone axes and biological systems, thus, establishing a link through which regulation by GH may occur. Clinical features of adult growth hormone deficiency (AGHD) include abnormal body composition, reduction in quality of life, osteoporosis and increased risk of cardiovascular mortality. In health, many of the factors which regulate these features demonstrate circadian rhythmicity and pulsatility. Furthermore, AGHD is associated with abnormalities in the periodic variation of such controlling factors. GH replacement therapy, administered in the form of timed, intermittent subcutaneous injections, results in improvement of many of the clinical effects of AGHD, and is associated with normalization of the temporal fluctuations. Currently, there remains scope for further investigation of the effects of AGHD and subsequent GHR on the circadian rhythmicity of many hormones and systems; and additional studies are required to understand the physiological significance of the changes observed to date.