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GH
Growth hormone (GH), also called somatotropin, is a peptide hormone secreted by somatotroph cells of the anterior pituitary. It promotes body growth, regulates protein, lipid, and carbohydrate metabolism, and stimulates production of insulin-like growth factor 1, particularly by the liver.
Region-
SystemEndocrine System
Growth hormone (GH), also called somatotropin, is a peptide hormone produced and secreted by somatotroph cells of the anterior pituitary. It is a major regulator of postnatal growth and also has important effects on protein synthesis, lipid metabolism, carbohydrate metabolism, and body composition.
GH acts both directly on target tissues and indirectly through insulin-like growth factor 1 (IGF-1). The liver is an important source of circulating IGF-1, although many other tissues also produce IGF-1 locally in response to GH. Together, GH and IGF-1 regulate growth of bone, cartilage, skeletal muscle, and numerous other tissues.
GH secretion is controlled primarily by the hypothalamic hormones growth hormone-releasing hormone (GHRH) and somatostatin. GHRH stimulates GH synthesis and release, while somatostatin inhibits secretion. The gastrointestinal hormone ghrelin also stimulates GH release. Secretion is pulsatile and varies with sleep, age, nutritional state, exercise, and other physiological factors.
Hormone Classification
GH is a peptide hormone consisting of a single polypeptide chain. The predominant human GH form contains 191 amino acids.
Because it is a peptide hormone, GH acts through a cell-surface receptor rather than directly entering target cells to bind an intracellular receptor.
Alternative Names
Growth hormone is also known as somatotropin or somatotropic hormone.
The abbreviation GH is widely used in clinical endocrinology and physiology.
Site of GH Production
GH is synthesized and secreted by somatotrophs located within the anterior pituitary, particularly the pars distalis of the adenohypophysis.
Somatotrophs constitute one of the major endocrine cell populations of the anterior pituitary.
Somatotroph Cells
Somatotrophs are specialized endocrine cells that synthesize, store, and secrete GH.
In traditional histological preparations, somatotrophs are classified among the acidophilic cells of the anterior pituitary because their cytoplasmic secretory granules stain with acidic dyes.
Anterior Pituitary
The anterior pituitary, or adenohypophysis, is the glandular portion of the pituitary gland. It contains somatotrophs together with lactotrophs, corticotrophs, thyrotrophs, and gonadotrophs.
Unlike hormones released from the posterior pituitary, GH is synthesized directly by pituitary endocrine cells rather than by hypothalamic neurons.
Hypothalamic Regulation
The hypothalamus regulates GH secretion through stimulatory and inhibitory signals delivered to the anterior pituitary through the hypothalamo-hypophyseal portal circulation.
GHRH provides a major stimulatory signal, while somatostatin provides a major inhibitory signal.
Growth Hormone-Releasing Hormone
Growth hormone-releasing hormone (GHRH) is synthesized by hypothalamic neurons and released into capillaries of the median eminence.
Portal vessels transport GHRH to the anterior pituitary, where it binds receptors on somatotrophs and stimulates GH synthesis and secretion.
Somatostatin
Somatostatin, also called growth hormone-inhibiting hormone, is an important physiological inhibitor of GH secretion.
Hypothalamic somatostatin reaches the anterior pituitary through the portal circulation and suppresses GH release from somatotrophs.
Ghrelin
Ghrelin is a peptide hormone produced predominantly by the stomach and also expressed within the central nervous system.
It activates the growth hormone secretagogue receptor and can strongly stimulate GH secretion. Ghrelin also participates in regulation of appetite and energy balance.
Major Regulators of GH
| Regulator | Source | General Effect on GH |
|---|---|---|
| GHRH | Hypothalamus | Stimulates GH synthesis and secretion |
| Somatostatin | Hypothalamus | Inhibits GH secretion |
| Ghrelin | Primarily stomach | Stimulates GH secretion |
| IGF-1 | Liver and other tissues | Provides negative feedback |
GH Secretory Pathway
| Step | Event |
|---|---|
| 1 | Hypothalamic neurons release GHRH and somatostatin |
| 2 | Regulatory hormones enter the primary capillary plexus at the median eminence |
| 3 | Hypophyseal portal vessels carry them to the anterior pituitary |
| 4 | GHRH and somatostatin regulate somatotroph activity |
| 5 | Somatotrophs release GH into pituitary capillaries |
| 6 | GH enters the systemic circulation |
| 7 | GH acts directly on tissues and stimulates IGF-1 production |
Pulsatile GH Secretion
GH is secreted in pulses rather than at a constant rate. Consequently, serum GH concentrations can vary substantially over relatively short periods.
This pulsatility is an important reason why a single random GH measurement generally provides limited information about overall GH secretion.
GH and Sleep
GH secretion is closely associated with sleep. A major secretory pulse commonly occurs after the onset of deep slow-wave sleep.
The relationship between sleep and GH secretion is particularly prominent in younger individuals.
Factors That Influence GH Secretion
| Factor | Typical Effect |
|---|---|
| GHRH | Increases GH |
| Somatostatin | Decreases GH |
| Ghrelin | Increases GH |
| Deep sleep | Promotes GH pulses |
| Exercise | Can increase GH |
| Hypoglycemia | Can increase GH |
| Fasting | Can increase GH secretion |
| IGF-1 | Provides negative feedback |
| Hyperglycemia | Can suppress GH secretion |
Growth Hormone Receptor
GH acts through the growth hormone receptor (GHR), a cell-surface receptor belonging to the cytokine receptor family.
GH binding promotes receptor conformational changes that activate intracellular signaling pathways, particularly the JAK-STAT pathway.
JAK-STAT Signaling
The growth hormone receptor is associated with Janus kinase 2 (JAK2). GH binding activates JAK2 and leads to phosphorylation of intracellular signaling proteins, including STAT transcription factors.
Activated STAT proteins move into the nucleus and regulate expression of GH-responsive genes.
GH Receptor Signaling
| Step | Event |
|---|---|
| 1 | GH binds the growth hormone receptor |
| 2 | Receptor-associated JAK2 is activated |
| 3 | Intracellular proteins are phosphorylated |
| 4 | STAT proteins are activated |
| 5 | Activated STATs enter the nucleus |
| 6 | Expression of GH-responsive genes changes |
Insulin-Like Growth Factor 1
Insulin-like growth factor 1 (IGF-1), historically called somatomedin C, mediates many of the growth-promoting effects associated with GH.
GH stimulates IGF-1 production in the liver and in multiple peripheral tissues. Circulating hepatic IGF-1 has systemic endocrine actions, while locally produced IGF-1 can act through paracrine and autocrine mechanisms.
IGF-1 Receptor
IGF-1 acts through the IGF-1 receptor, a receptor tyrosine kinase structurally related to the insulin receptor.
Activation of this receptor stimulates intracellular pathways involved in cell proliferation, differentiation, survival, and protein synthesis.
GH-IGF-1 Axis
| Level | Hormone or Structure | Major Function |
|---|---|---|
| Hypothalamus | GHRH and somatostatin | Regulate pituitary GH secretion |
| Anterior pituitary | GH | Acts directly on tissues and stimulates IGF-1 production |
| Liver and peripheral tissues | IGF-1 | Mediates many growth-promoting effects |
| Target tissues | Bone, cartilage, muscle and others | Growth and tissue remodeling |
Direct and Indirect Effects of GH
GH produces both direct metabolic effects and growth effects mediated substantially through IGF-1.
| Type of Effect | Examples |
|---|---|
| Direct GH effects | Lipolysis, altered glucose metabolism, stimulation of protein synthesis |
| GH-IGF-1 effects | Longitudinal bone growth, cartilage growth, cellular proliferation and tissue growth |
Growth of Long Bones
Before epiphyseal closure, GH and IGF-1 promote longitudinal bone growth at the epiphyseal growth plates.
They stimulate proliferation and differentiation of growth plate chondrocytes and support production of extracellular matrix and new bone.
Epiphyseal Growth Plate
The epiphyseal growth plate is a specialized cartilage structure located between the epiphysis and metaphysis of growing long bones.
Growth plate chondrocytes proliferate, hypertrophy, and contribute to a cartilage scaffold that is progressively replaced by bone through endochondral ossification.
GH and Chondrocytes
GH can act directly on growth plate cells and also stimulates local IGF-1 production.
IGF-1 promotes chondrocyte proliferation and matrix synthesis, contributing to expansion of growth plate cartilage and longitudinal skeletal growth.
Epiphyseal Closure
At the end of puberty, growth plates progressively close under the influence of sex steroids, particularly estrogen signaling in both sexes.
After epiphyseal closure, excess GH can no longer substantially increase long-bone length, although it can continue to alter bone thickness and soft-tissue growth.
GH and Bone Remodeling
GH and IGF-1 continue to influence bone after linear growth has ended. They affect osteoblast activity, bone turnover, and skeletal remodeling.
Chronic GH excess in adults can therefore cause characteristic changes in the skull, jaw, hands, feet, and other skeletal structures despite closed growth plates.
GH and Skeletal Muscle
GH supports growth and maintenance of skeletal muscle through effects on amino acid uptake, protein synthesis, metabolism, and interactions with IGF-1.
Its anabolic effects contribute to increased lean body mass under appropriate physiological conditions.
Protein Metabolism
GH generally promotes protein anabolism. It increases amino acid uptake and protein synthesis in multiple tissues and can reduce protein breakdown under certain conditions.
These effects support tissue growth and maintenance of lean body mass.
Lipid Metabolism
GH promotes lipolysis in adipose tissue, increasing mobilization of fatty acids from triglyceride stores.
This provides fatty acids as an energy source and contributes to the characteristic effects of GH on body composition.
Carbohydrate Metabolism
GH has important effects on glucose metabolism and can oppose some actions of insulin.
Excess GH reduces insulin sensitivity in peripheral tissues and can increase hepatic glucose production, potentially contributing to hyperglycemia.
Anti-Insulin Effects
At elevated concentrations, GH can produce insulin-antagonistic effects by decreasing glucose uptake in certain tissues and increasing glucose availability.
Chronic GH excess can therefore produce insulin resistance and increase the risk of abnormal glucose tolerance or diabetes mellitus.
Major Metabolic Effects
| Metabolic Area | Major GH Effect |
|---|---|
| Protein | Promotes protein synthesis and anabolic activity |
| Fat | Promotes lipolysis and fatty acid mobilization |
| Carbohydrate | Reduces insulin sensitivity and helps preserve circulating glucose |
| Body composition | Supports lean tissue and reduces fat mass under physiological conditions |
GH During Fasting
GH secretion can increase during fasting. Its metabolic actions help mobilize fat and reduce dependence on glucose oxidation in some tissues.
These effects contribute to metabolic adaptation when nutrient availability is reduced.
GH and Exercise
Exercise can stimulate GH secretion, although the response varies with exercise intensity, duration, training status, age, nutritional state, and other factors.
Exercise-associated GH secretion participates in metabolic and tissue responses to physical activity.
GH and Age
GH secretion changes substantially throughout life. Secretion is relatively high during periods of rapid growth and typically reaches prominent levels during puberty.
Average GH secretion and pulse amplitude generally decline with advancing age.
GH During Puberty
Puberty is associated with increased activity of the GH-IGF-1 axis. Sex steroids interact with this system and contribute to the pubertal growth spurt.
IGF-1 concentrations typically increase during puberty and subsequently decline in adulthood.
Negative Feedback
The GH-IGF-1 axis is regulated through negative feedback. IGF-1 can reduce GH secretion at the pituitary and influence hypothalamic regulatory pathways.
GH itself can also participate in short-loop feedback mechanisms affecting hypothalamic regulation.
IGF-1 Feedback
Elevated IGF-1 tends to suppress further GH secretion. This occurs through direct pituitary effects and through changes in hypothalamic GHRH and somatostatin signaling.
This feedback mechanism helps prevent uncontrolled activity of the growth axis.
GH and Prolactin
GH and prolactin are structurally related peptide hormones produced by acidophilic cell lineages of the anterior pituitary.
Despite their structural relationship, GH primarily regulates growth and metabolism, while prolactin is principally involved in mammary gland development and lactation.
GH Versus Prolactin
| Feature | GH | Prolactin |
|---|---|---|
| Pituitary cell | Somatotroph | Lactotroph |
| Major stimulatory regulator | GHRH | Multiple factors, with secretion normally restrained by dopamine |
| Major inhibitor | Somatostatin | Dopamine |
| Major function | Growth and metabolism | Lactation |
| Important signaling pathway | JAK-STAT | JAK-STAT |
GH Versus IGF-1
| Feature | GH | IGF-1 |
|---|---|---|
| Major source | Anterior pituitary | Liver and peripheral tissues |
| Regulation | GHRH, somatostatin, ghrelin and feedback | Strongly stimulated by GH |
| Secretion pattern | Highly pulsatile | More stable circulating concentration |
| Major role | Direct metabolic actions and stimulation of IGF-1 | Mediates many growth-promoting actions |
| Receptor type | Cytokine receptor family | Receptor tyrosine kinase |
Growth Hormone Deficiency
Growth hormone deficiency results from inadequate GH secretion or abnormalities affecting the hypothalamic-pituitary growth axis.
The manifestations depend strongly on the age at which the deficiency occurs.
GH Deficiency in Children
GH deficiency during childhood can cause reduced linear growth and decreased growth velocity.
Children may have proportionate short stature when GH deficiency occurs without other major skeletal abnormalities.
GH Deficiency in Adults
Adult GH deficiency does not cause loss of achieved skeletal height but can affect body composition, exercise capacity, bone metabolism, lipid metabolism, and quality of life.
It frequently occurs in association with other hypothalamic or pituitary disorders.
Causes of GH Deficiency
GH deficiency can result from congenital abnormalities, genetic defects, hypothalamic disease, pituitary tumors, surgery, radiation, trauma, inflammation, or other structural lesions affecting the hypothalamic-pituitary region.
Deficiency can occur in isolation or as part of broader hypopituitarism.
Growth Hormone Excess
Persistent excessive GH secretion is most commonly associated with a GH-secreting pituitary tumor arising from somatotroph cells.
The clinical phenotype depends substantially on whether GH excess develops before or after epiphyseal growth plate closure.
Gigantism
Gigantism results when severe GH excess occurs before epiphyseal closure.
Excessive stimulation of growth plates produces markedly increased linear growth and extreme height, accompanied by other effects of GH and IGF-1 excess.
Acromegaly
Acromegaly results from chronic GH excess after epiphyseal closure. Because long bones can no longer increase substantially in length, growth occurs predominantly through enlargement and thickening of bones and soft tissues.
Characteristic changes can involve the hands, feet, facial bones, jaw, skin, soft tissues, and internal organs.
Acromegaly and the Skeleton
Chronic GH and IGF-1 excess can produce enlargement of the mandible, increased prominence of facial bones, thickening of the calvarium, enlargement of the hands and feet, and changes in joint structures.
These changes reflect continued effects on bone remodeling and soft tissues despite closure of the epiphyseal plates.
Metabolic Effects of GH Excess
Chronic GH excess can cause substantial insulin resistance. Compensatory hyperinsulinemia may initially maintain glucose concentrations, but impaired glucose tolerance or diabetes mellitus can develop.
GH excess can also alter lipid metabolism, cardiovascular function, and body composition.
Somatotroph Pituitary Tumors
GH-secreting pituitary tumors arise from somatotroph lineage cells of the adenohypophysis.
In addition to endocrine manifestations of GH excess, larger tumors can produce local mass effects involving the optic chiasm, cavernous sinus, normal pituitary tissue, or other structures around the sella turcica.
GH and the Optic Chiasm
A large pituitary tumor can extend superiorly from the sella turcica and compress the optic chiasm.
This can produce visual field abnormalities, classically involving the temporal fields of both eyes.
Measurement of GH
Because GH secretion is strongly pulsatile, a single random serum GH measurement is often difficult to interpret.
Evaluation of the GH axis therefore frequently relies on IGF-1 measurement and dynamic testing appropriate to the suspected disorder.
IGF-1 Measurement
Serum IGF-1 is more stable throughout the day than GH and reflects integrated activity of the GH axis.
Interpretation requires comparison with age-appropriate reference ranges because normal IGF-1 concentrations vary substantially with age.
Oral Glucose Suppression Test
Oral glucose normally suppresses GH secretion. Failure of GH to suppress appropriately after a glucose load can support the biochemical evaluation of suspected acromegaly.
Interpretation depends on the assay and clinical context.
GH Stimulation Testing
Because normal individuals can have very low GH concentrations between secretory pulses, suspected GH deficiency generally cannot be established from a random low GH concentration alone.
Dynamic stimulation tests can be used to assess the ability of the hypothalamic-pituitary system to produce an appropriate GH response.
Recombinant Growth Hormone
Recombinant human growth hormone can be used therapeutically in selected conditions associated with GH deficiency or impaired growth.
Treatment requires appropriate diagnosis and monitoring because excessive GH exposure can produce metabolic and tissue effects resembling endogenous GH excess.
GH Receptor Resistance
Normal or elevated GH concentrations cannot produce normal growth when target tissues are unable to respond adequately to the hormone.
Severe GH receptor dysfunction causes profound reduction in IGF-1 production despite increased circulating GH.
Laron Syndrome
Laron syndrome is a form of severe growth hormone insensitivity caused by abnormalities affecting GH receptor function.
Patients typically have elevated or normal-high GH concentrations with markedly reduced IGF-1 and impaired postnatal growth.
GH Deficiency Versus GH Resistance
| Feature | GH Deficiency | GH Resistance |
|---|---|---|
| Primary problem | Insufficient GH secretion | Impaired response to GH |
| GH | Insufficient response on appropriate testing | Often elevated |
| IGF-1 | Often reduced | Reduced |
| Defect location | Hypothalamic-pituitary axis | GH receptor or post-receptor pathway |
GH and Pituitary Anatomy
GH physiology is closely related to the anatomy of the hypothalamus, pituitary stalk, portal circulation, and adenohypophysis.
Damage at different levels can alter GH secretion through distinct mechanisms. Hypothalamic disease can impair GHRH or somatostatin signaling, stalk lesions can disrupt portal delivery, and anterior pituitary disease can directly damage somatotrophs.
GH in Hypopituitarism
GH deficiency can occur as part of hypopituitarism caused by structural or functional disease of the hypothalamic-pituitary region.
When multiple pituitary hormones are deficient, assessment of the entire anterior pituitary hormonal profile is important.
Key Features of Growth Hormone
| Feature | Key Point |
|---|---|
| Full name | Growth hormone |
| Alternative name | Somatotropin |
| Hormone class | Peptide hormone |
| Major form | 191-amino-acid polypeptide |
| Source | Anterior pituitary somatotrophs |
| Major stimulatory hypothalamic hormone | GHRH |
| Major inhibitory hypothalamic hormone | Somatostatin |
| Additional stimulant | Ghrelin |
| Secretion pattern | Pulsatile |
| Major receptor pathway | JAK2-STAT |
| Important mediator | IGF-1 |
| Major growth targets | Bone, cartilage, skeletal muscle and other tissues |
| Major metabolic effects | Protein anabolism, lipolysis and altered glucose metabolism |
| Childhood excess | Gigantism |
| Adult excess | Acromegaly |
Anatomical and Physiological Importance
Growth hormone forms the central pituitary component of the GH-IGF-1 axis. Hypothalamic neurons regulate somatotroph activity through GHRH and somatostatin delivered to the anterior pituitary by the hypothalamo-hypophyseal portal circulation. Somatotrophs then release GH into the systemic circulation in a strongly pulsatile pattern.
Once in the circulation, GH acts directly on numerous tissues through growth hormone receptors and stimulates production of IGF-1 in the liver and peripheral tissues. GH receptor activation primarily uses JAK2-STAT signaling, whereas IGF-1 acts through a receptor tyrosine kinase. These complementary pathways coordinate cellular growth, differentiation, metabolism, and tissue remodeling.
In the developing skeleton, the GH-IGF-1 axis is particularly important at the epiphyseal growth plates. Stimulation of chondrocyte proliferation and differentiation contributes to longitudinal growth of long bones before epiphyseal closure. After the growth plates close, GH can no longer produce substantial increases in long-bone length, but it continues to influence bone remodeling and soft-tissue growth.
GH also has major direct metabolic actions. It promotes protein synthesis, stimulates mobilization of fatty acids from adipose tissue, and reduces insulin sensitivity under some conditions. These actions help coordinate nutrient use with growth and contribute to metabolic adaptation during fasting, exercise, and other physiological states.
The anatomical level at which the GH axis is disrupted determines the resulting disorder. Hypothalamic disease can alter GHRH or somatostatin signaling, pituitary disease can impair or increase somatotroph secretion, and peripheral receptor abnormalities can produce GH resistance. Excess GH before epiphyseal closure causes gigantism, whereas chronic excess after closure produces acromegaly. Insufficient GH during childhood can substantially impair linear growth.
Through its origin in anterior pituitary somatotrophs, hypothalamic regulation, pulsatile secretion, GH receptor signaling, stimulation of IGF-1, and effects on skeletal and metabolic tissues, growth hormone is a major endocrine regulator of human growth, body composition, and metabolism.
Published on October 1, 2026
Last updated on October 1, 2026
Last updated on October 1, 2026