Growth hormone (GH) is a hormone made up of 191 amino acids that are produced and secreted by the so-called somatotroph cells of the anterior pituitary gland. This hormone controls several complex physiological processes including growth and metabolism. The growth hormone is also of considerable interest as a medication for using in both humans and animals.
Physiological Effects of the Growth Hormone
To truly understand actions of the growth hormone it is necessary to divide its effects into two groups:
• Direct effect: the growth hormone binds to receptors on target cells. Fat cells (adipocytes), for example, have growth hormone receptors. So, the growth hormone causes fat cells to break down into triglycerides and suppresses their ability to take up and accumulate circulating lipids.
• Indirect effect: the growth hormone causes secretion of IGF-1, an insulin-like growth factor hormone. The liver and other tissues secrete IGF-1 in response to growth hormone. Growth effects of the growth hormone are mostly related to the action of IGF-I.
Keeping this distinction in mind, we can discuss two major roles that the growth hormone and IGF-I play in physiology.
Growth is a very complex process, and requires the coordinated action of several hormones. The major role of growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-I. IGF-I stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes.
IGF-I is also a key participant of the muscle growth. It stimulates both the differentiation and proliferation of myoblasts (muscle cells), and amino acid uptake and protein synthesis in muscle and other tissues.
Influence On Metabolism
Growth hormone exerts its action on protein, lipid and carbohydrate metabolism. In some cases, it is the growth hormone that shows a direct effect; in other cases IGF-I is a critical mediator. Sometimes, there are both direct and indirect effects.
• Protein metabolism: In general, the growth hormone stimulates protein anabolism in many tissues. This means increased amino acid uptake, increased protein synthesis and decreased oxidation of proteins.
• Fat metabolism: The growth hormone increases the utilization of fat by stimulating triglyceride breakdown and adipocytes oxidation (fat cells).
• Carbohydrate metabolism: The growth hormone is one of those hormones that take part in the process of maintaining blood glucose level within a normal range. The growth hormone is often said to have anti-insulin activity, because it suppresses the ability of insulin to stimulate glucose uptake in peripheral tissues, and increases glucose synthesis in the liver. Strange as it may seem but the growth hormone stimulates insulin secretion leading to hyperinsulinemia.
Growth Hormone Secretion
Production of growth hormone is modulated by many factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, production of the growth hormone is primary regulated by two hypothalamic hormones and one stomach hormone:
• Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both synthesis and secretion of the growth hormone.
• Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus. The somatostatin inhibits the growth hormone in response to GHRH and to other stimulatory factors such as low glucose concentration in blood.
• Ghrelin is a peptide hormone secreted in the stomach. The ghrelin binds to somatotrophs receptors and stimulates the growth hormone secretion.
The growth hormone secretion is also very much influenced by IGF-I.
High blood levels of IGF-I lead to decreased secretion of the growth hormone not only because of direct suppression of the somatotrophs, but also because of stimulation of somatostatin release by the hypothalamus.
The growth hormone also responds by inhibiting GHRH secretion and, possibly, has a direct (autocrine) inhibitory effect on secretion in the somatotroph.
Different factors affect differently the growth hormone synthesis and secretion, so production of the growth hormone has a pulsating “pattern”. Usual concentrations of the growth hormone in blood are very low. The highest levels of the growth hormones are observed in children and teenagers some time after deep sleep.
The results of clinical studies of the growth hormone clearly identified the role that the growth hormone plays in normal physiology. Such disorders may say about pathology of the hypothalamus, the pituitary or target cells. Growth hormone deficiency may be determined not only by the deficiency of growth hormone secretion, but also by target cells response.
Clinically, growth hormone deficiency or binding-to-receptor defects lead to retardation of growth or dwarfism. Presentation of growth hormone deficiency depends on the age in which deficiency started developing, and may be determined by some heritable or acquired disease.
Excessive secretion of the growth hormone is also dependent on the age in which it started developing, and may lead to two different disorders:
• Gigantism is the result of excessive growth hormone secretion that started developing in childhood or juvenile age. It is a very rare disorder usually determined by somatotrophs tumor. One of the most famous giants was a man named Robert Wadlow. He weighed only 8.5 pounds at birth, but weighed 105 pounds and was 5 feet 4 inches tall at the age of 5. Robert reached an adult weight of 490 pounds and 8 feet 11 inches in height. He died at the age of 22.
• Acromegaly results from excessive secretion of growth hormone in adults, and usually determined by pituitary tumor. This disorder is typically asymptomatic and presenting during several years. Clinical signs of acromegaly include overgrowth of extremities, soft-tissue swelling, abnormalities of jaw structure and cardiac diseases. The excessive growth hormone and IGF-I levels also lead to a number of metabolic disorders including hyperglycemia.