Growth Hormone and IGF-1 Axis

Growth hormone is secreted by the anterior pituitary under hypothalamic control and acts both directly on tissues and, importantly, by inducing insulin-like growth factor 1 (IGF-1), produced largely by the liver. This growth hormone-IGF-1 axis drives longitudinal bone growth in childhood and influences metabolism throughout life, integrating signals from the hypothalamus, pituitary, and peripheral tissues.

Definition

The growth hormone-IGF-1 axis comprises hypothalamic growth-hormone-releasing hormone and somatostatin, pituitary growth hormone (somatotropin), and insulin-like growth factor 1 (IGF-1); growth hormone stimulates IGF-1 production, and the two together promote growth and modulate metabolism, with IGF-1 providing negative feedback.

Scope

The entry covers the regulation of growth hormone secretion, the somatomedin (IGF-1) mechanism through which many of its growth effects are mediated, the axis's pulsatile and feedback-controlled nature, and its metabolic actions. It is a reference physiology topic and does not provide guidance on diagnosing or treating growth or pituitary disorders.

Core questions

• How is growth hormone secretion regulated by the hypothalamus and by feedback?
• How does growth hormone act both directly and through IGF-1?
• What are the growth and metabolic actions of the axis across the lifespan?

Key concepts

• Growth-hormone-releasing hormone (GHRH)
• Somatostatin (GH-inhibiting)
• Pulsatile growth hormone secretion
• Insulin-like growth factor 1 (IGF-1)
• Negative feedback by IGF-1
• Direct versus IGF-1-mediated actions

Key theories

Somatomedin hypothesis

The proposal that many of growth hormone's growth-promoting effects are not direct but are mediated by a circulating, liver-derived factor (somatomedin, now IGF-1) whose production growth hormone stimulates; the hypothesis has since been refined to include local, tissue-level IGF-1 production.

Mechanisms

Hypothalamic growth-hormone-releasing hormone stimulates, and somatostatin inhibits, the release of growth hormone from anterior-pituitary somatotrophs, producing a pulsatile secretion pattern. Growth hormone acts directly on some tissues but exerts much of its growth-promoting effect by inducing IGF-1, made chiefly in the liver and also locally in target tissues, in line with the somatomedin hypothesis. IGF-1 promotes growth of bone and other tissues and feeds back on the hypothalamus and pituitary to restrain further growth hormone release. Beyond growth, the axis has metabolic actions, including effects on glucose, lipid, and protein handling.

Clinical relevance

The growth hormone-IGF-1 axis underlies normal childhood growth and adult metabolic regulation, and understanding it provides the physiological background for conditions of hormone excess or deficiency. This entry describes normal physiology for educational orientation and is not a basis for individual diagnosis or treatment.

Evidence & guidelines

The axis is grounded in the somatomedin hypothesis, traced to Salmon and Daughaday's 1957 identification of a growth-hormone-dependent serum factor and refined in later reviews. Subsequent reviews have synthesised the metabolic actions of growth hormone and the history and physiology of the axis. The topic rests on this primary and review literature rather than a single clinical guideline.

History

In 1957 Salmon and Daughaday found that serum contained a growth-hormone-dependent factor that stimulated cartilage, leading to the somatomedin hypothesis: that growth hormone acts largely through a circulating intermediary. This factor was later identified as insulin-like growth factor 1, and the hypothesis was refined to include locally produced IGF-1, shaping the modern understanding of the growth hormone-IGF-1 axis.

Key figures

• William H. Daughaday
• Derek Le Roith
• Michael B. Ranke

Seminal works

• salmon-daughaday-1957
• leroith-2001

Frequently asked questions

Does growth hormone act directly or through another hormone?

Both: growth hormone has some direct actions, but many of its growth-promoting effects are mediated by IGF-1, which it stimulates the liver and other tissues to produce, as described by the somatomedin hypothesis.

How is the growth hormone-IGF-1 axis kept in balance?

Hypothalamic GHRH and somatostatin set growth hormone release, and IGF-1 provides negative feedback on the hypothalamus and pituitary, restraining further growth hormone secretion.