Growth Hormone

Growth Hormone Function

Growth hormone has direct metabolic effects on tissues by binding to cell surface receptors, and indirect effects by stimulating liver cells to produce insulin-like growth factors (IGFs), also known as somatomedins. The most important IGF is IGF-1.

Growth hormone, either directly or indirectly, affects almost every tissue in the body, with particularly important effects on skeletal muscle and cartilage cells (chondrocytes). The overall effects of growth hormone and IGF-1 are essential for skeletal growth, bone density, muscle strength and cardiac function.

Direct Effects

Effects of growth hormone itself include:

• Lipolysis – released fatty acids are used to generate ATP, thereby sparing glucose
• Glycogenolysis in the liver – glycogen is broken down to glucose, raising blood glucose levels with a diabetogenic effect
• Epithelial and connective tissue growth and repair – by stem cell division and differentiation

Indirect Effects

The effects of IGF-1 can be thought of as “anabolic” (compound building), similar to insulin. These include:

• Protein synthesis and cell growth
• Carbohydrate oxidation

IGF-1 is particularly important after a meal, when glucose and amino acids are readily available in the bloodstream. Whilst insulin promotes glucose uptake for ATP synthesis, IGF-1 binds to plasma membrane proteins promoting amino acid uptake and usage of this energy in protein synthesis.

Regulation of Growth Hormone

Hypothalamic Control of Growth Hormone

The hypothalamus secretes growth hormone releasing-hormone (GHRH), which stimulates somatotroph cells of the anterior pituitary to release growth hormone.

Other Factors

Several factors modulate growth hormone secretion, including stress, exercise, nutritional status, sleep, and hormones such as ghrelin, which is synthesised by the stomach.

The growth hormone axis differs from the typical endocrine axis. While hypothalamic GHRH promotes growth hormone release, the hypothalamus also produces growth hormone inhibiting hormone (also known as somatostatin) which inhibits growth hormone secretion.

Negative Feedback

Insulin-like growth factors directly suppress growth hormone secretion from somatotroph cells.

They also indirectly suppress growth hormone secretion by inhibiting GHRH release and stimulating somatostatin release.

Created in BioRender

Fig 1
Regulation of the Hypothalamic–Pituitary–Growth Hormone Axis

Clinical Relevance

Growth Hormone Excess

In children, growth hormone hypersecretion before fusion of the bony epiphyses results in gigantism, characterised by excessive linear growth and tall stature.

In adults, excess growth hormone causes acromegaly and is mostly due to a growth hormone-secreting pituitary tumour.

Clinical features include:

• Enlargement of the hands, feet, and jaw
• Paraesthesia in the extremities
• Amenorrhoea
• Coarse facial features, including a wide nose and rounded face
• Hypertension
• Cardiomegaly (enlargement of the heart)

Treatment includes surgical removal of the pituitary tumour, typically via the sphenoid bone (“transsphenoidal” approach) if the tumour is large enough, or medical management using somatostatin analogues.

Philippe Chanson and Sylvie Salenave, CC BY 2.0 <https://creativecommons.org/licenses/by/2.0>, via Wikimedia Commons

Fig 2
Facial features of a patient with acromegaly