Growth hormone

Growth hormone (GH) is a peptide hormone that is secreted by cells called somatotrophs in the anterior pituitary. GH is a stress hormone that raises the concentration of glucose and free fatty acids. It also stimulates production of growth factor 1 (IGF-1). A recombinant form of GH called somatropin (INN) is used as a prescription drug to treat children's growth disorders and adult growth hormone deficiency.

Physiologic effect of growth hormone

The main action of GH is to stimulate linear growth in children; however, it also fosters a healthy body composition by increasing muscle and reducing fat mass, maintains normal blood glucose levels, and promotes a favorable lipid profile (Pic. 1). 

Growth hormone has many other effects on the body:

• increases calcium retention and strengthens and increases the mineralization of bone
• increases muscle mass through increased volume (hypertrophy) of the sarcomere
• promotes lipolysis (burning of fat)
• increases protein synthesis
• stimulates the growth of all internal organs excluding the brain
• plays a role in homeostasis (property of the system)
• reduces liver uptake of glucose
• promotes synthesis of glucose from nonsugar precursors (gluconeogenesis) in the liver
• contributes to the maintenance and function of pancreatic islets
• stimulates the immune system
• increases deiodination of thyroid hormones T4 to T3

Effects on growth

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells.

Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms:

• Because polypeptide hormones are not fat-soluble, they cannot penetrate cell membranes. Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway (signaling cascade that plays a crucial role in a variety of cell regulatory events). Through this mechanism GH directly stimulates division and multiplication of cartilage cells (chondrocytes).

• GH also stimulates, through the JAK-STAT signaling pathway (transmits information from signals outside the cells to the nucleus), the production of insulin-like growth factor 1 (IGF-1), formerly known as somatomedin C, a hormone homologous to proinsulin. The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide variety of tissues. Additional IGF-1 is generated within target tissues, making it what appears to be both an endocrine and an autocrine/paracrine hormone. IGF-1 also has stimulatory effects on osteoblast (bone cells) and chondrocyte activity to promote bone growth.

Control of growth hormone secretion

GH secretion mechanism is regulated by some hormones, principally the growth hormone releasing hormone (GHRH), the somatostatin (STT) and the Ghrelin. GHRH is a peptide produced in the hypothalamus that activates the production in and release of GH from the pituitary; GHRH binds to specific receptors. However, STT is peptidic hormone inhibiting the release but not the GH production; STT is present in the hypothalamus but also in other part of central nervous system and other tissues. The final result is an arrest of GH secretion from the cells.

GH secretion is also related to external mechanisms, such as stress, hypoglycaemia (low blood sugar), sex hormones secretion, starvation, sleep or exercise, all condition increasing its secretion. A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Young adolescents secrete GH at the rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day. Sleep deprivation generally suppresses GH release, particularly after early adulthood.

Pathological conditions

Growth hormone deficiency

Growth hormone deficiency (GHD) represents a condition characterized by reduced GH secretion, isolated or associated with other pituitary hormone deficiencies. 

Also, GH is a necessary factor for optimal female fertility, as evidenced by the decreased (but not absent) fertility in GHD women and the ability of GH replacement to enable successful unassisted pregnancies in previously infertile GHD women . These beneficial and detrimental effects of GH reflect the production and action of GH in the ovary and uterus.
Growth hormone–deficient men have small-sized testes. The growth hormone acts to promote sperm production, and it is impaired in GHD men.

Growth hormone excess

Gigantism is a rare disorder resulting from increased levels of growth hormone before the fusion of the growth plate which usually occurs at some point soon after puberty. This is most often due to abnormal tumor growths on the pituitary gland. Gigantism should not be confused with acromegaly, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.

Therapeutical use

GH therapy not only increases linear growth velocity, but also promotes maintenance of healthy body composition (increased muscle and reduced fat mass), normal blood glucose levels, and a favorable lipid profile.

Several studies, primarily involving patients with GH deficiency, have suggested a crucial role of GH in both mental and emotional well-being and maintaining a high energy level. Adults with GH deficiency often have higher rates of depression than those without. While GH replacement therapy has been proposed to treat depression as a result of GH deficiency, the long-term effects of such therapy are unknown.

GH has also been studied in the context of cognitive function, including learning and memory. GH in humans appears to improve cognitive function and may be useful in the treatment of patients with cognitive impairment that is a result of GH deficiency.