Internal medicine

Endocrinology

Acromegaly

Short stature

Growth hormone deficiency

Growth hormone

Human growth hormone

Physiology

Bioinformatics

Hormone

Medicine

Biology

Nature Reviews Endocrinology

In this Review, the authors chart the history of growth hormone, from discovery to clinical development and therapeutic approval, and discuss the emerging pathophysiology and treatment of its related growth disorders, particularly in childhood. Finally, more recent developments and future strategies are highlighted. Growth hormone (GH) research and its clinical application for the treatment of growth disorders span more than a century. During the first half of the 20th century, clinical observations and anatomical and biochemical studies formed the basis of the understanding of the structure of GH and its various metabolic effects in animals. The following period (1958–1985), during which pituitary-derived human GH was used, generated a wealth of information on the regulation and physiological role of GH — in conjunction with insulin-like growth factors (IGFs) — and its use in children with GH deficiency (GHD). The following era (1985 to present) of molecular genetics, recombinant technology and the generation of genetically modified biological systems has expanded our understanding of the regulation and role of the GH–IGF axis. Today, recombinant human GH is used for the treatment of GHD and various conditions of non-GHD short stature and catabolic states; however, safety concerns still accompany this therapeutic approach. In the future, new therapeutics based on various components of the GH–IGF axis might be developed to further improve the treatment of such disorders. In this Review, we describe the history of GH research and clinical use with a particular focus on disorders in childhood.

Growth hormone — past, present and future