The secretion of hypothalamic, pituitary, and target tissue hormones is under tight regulatory control by a series of feedback and feed- forward loops. This complexity can be demonstrated using the growth hormone (GH) regulatory system as an example. The stimulatory substance growth hormone releasing hormone (GHRH) and the inhibitory substance somatostatin (SS) both products of the hypothalamus, control pituitary GH secretion. Somatostatin is also called growth hormone-inhibiting hormone (GHIH). Under the influence of GHRH, growth hormone is released into the systemic circulation, causing the target tissue to secrete insulin-like growth factor-1, IGF-1. Growth hormone also has other more direct metabolic effects; it is both hyperglycemic and lipolytic. The principal source of systemic IGF-1 is the liver, although most other tissues secrete and contribute to systemic IGF-1. Liver IGF-1 is considered to be the principal regulator of tissue growth. In particular, the IGF-1 secreted by the liver is believed to synchronize growth throughout the body, resulting in a homeostatic balance of tissue size and mass. IGF-1 secreted by peripheral tissues is generally considered to be autocrine or paracrine in its biological action.
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In patients with glucocorticoid-induced osteoporosis, Forteo increased lumbar spine BMD compared with baseline at 3 months through 18 months of treatment. In patients treated with Forteo, the mean percent change in BMD from baseline to endpoint was % at the lumbar spine, % at the total hip, and % at the femoral neck (p< all sites). The relative treatment effects of Forteo were consistent in subgroups defined by gender, age, geographic region, body mass index, underlying disease, prevalent vertebral fracture, baseline glucocorticoid dose, prior bisphosphonate use, and glucocorticoid discontinuation during trial.