“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Saturday, August 9, 2025

Growth hormones


Introduction and Definition

Human Growth Hormone (HGH), scientifically referred to as somatotropin, is a peptide hormone composed of 191 amino acids and synthesized by the somatotroph cells of the anterior pituitary gland. It plays a central role in stimulating growth, cell reproduction, and cellular regeneration in humans. Its functions extend beyond childhood growth to include regulation of body composition, metabolism, and tissue repair throughout life. HGH exerts its effects both directly and indirectly via stimulation of insulin-like growth factor 1 (IGF-1), primarily produced in the liver.

Regulation of Secretion

The release of HGH is tightly controlled by the hypothalamic–pituitary axis:

  • Growth Hormone–Releasing Hormone (GHRH): Produced by the hypothalamus, it stimulates GH secretion from the pituitary.

  • Somatostatin (Growth Hormone–Inhibiting Hormone, GHIH): Also produced by the hypothalamus, it inhibits GH release.

  • Ghrelin: Produced in the stomach and hypothalamus, it enhances GH secretion and acts synergistically with GHRH.

Secretion occurs in a pulsatile manner, with 10–20 pulses per day. The largest peak is observed shortly after the onset of deep sleep (slow-wave sleep). Secretion is higher in children and adolescents, gradually declining with age. Exercise, stress, trauma, fasting, and certain amino acids (e.g., arginine) can increase secretion, while hyperglycemia, obesity, and elevated circulating IGF-1 suppress it.

Mechanism of Action

HGH binds to specific growth hormone receptors (GHR) on target cells, initiating receptor dimerization and activation of the Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway. This triggers transcription of GH-responsive genes. A major outcome is increased hepatic production of IGF-1, which mediates most of GH’s growth-promoting effects, including stimulation of osteoblasts, chondrocytes, and muscle cell proliferation. GH also has IGF-1–independent actions, such as promoting lipolysis and influencing carbohydrate metabolism.

Physiological Roles

Skeletal and Cartilage Growth

  • Stimulates epiphyseal plate activity in growing bones.

  • Enhances chondrocyte proliferation and differentiation.

  • Promotes bone remodeling and density maintenance in adults.

Muscle and Protein Metabolism

  • Increases amino acid uptake and protein synthesis.

  • Reduces protein catabolism, thereby preserving lean body mass.

Adipose Tissue and Lipid Metabolism

  • Stimulates lipolysis, increasing free fatty acid availability for energy.

  • Reduces fat mass, particularly visceral fat, in physiological balance.

Carbohydrate Metabolism

  • Exhibits anti-insulin effects by reducing glucose uptake in peripheral tissues and promoting hepatic gluconeogenesis.

  • At high levels, may induce insulin resistance.

Cardiovascular and Organ Health

  • Supports myocardial contractility and cardiac output.

  • Influences vascular tone and lipid profile regulation.

Neurocognitive and Psychological Effects

  • Contributes to mood regulation, cognitive function, and psychological well-being.

  • Deficiency in adults is often associated with fatigue, depression, and reduced quality of life.

Growth Hormone Deficiency (GHD)

Etiology

  • Congenital causes: Genetic mutations affecting GH synthesis, secretion, or receptor function.

  • Acquired causes: Pituitary tumors, surgery, radiation therapy, traumatic brain injury, infiltrative diseases, or idiopathic origins.

Clinical Presentation

  • Children: Short stature, delayed skeletal maturation, increased adiposity, immature facial features.

  • Adults: Decreased lean body mass, increased fat mass, dyslipidemia, low bone mineral density, reduced exercise capacity, mood disturbances.

Diagnosis

  • Measurement of serum IGF-1 levels (low in most GHD cases).

  • Stimulation tests (insulin tolerance test, arginine, clonidine, glucagon) to assess pituitary GH reserve.

  • MRI imaging to evaluate pituitary and hypothalamic anatomy.

Excess Growth Hormone

Gigantism

  • Results from GH excess before epiphyseal plate closure in children.

  • Presents with extreme linear growth, increased muscle mass, and organomegaly.

Acromegaly

  • GH excess after epiphyseal closure in adults.

  • Characterized by enlargement of hands, feet, jaw, and facial features, thickened skin, and deepened voice.

  • Associated complications include hypertension, insulin resistance, diabetes mellitus, sleep apnea, cardiomegaly, and increased risk of certain cancers.

Causes

  • Most cases are due to pituitary adenomas secreting GH.

  • Rarely caused by ectopic production of GHRH or GH by non-pituitary tumors.

Therapeutic Uses of Recombinant HGH

Approved Indications in Children

  • Growth hormone deficiency.

  • Turner syndrome.

  • Prader–Willi syndrome.

  • Chronic kidney disease with growth failure.

  • Idiopathic short stature.

  • Children born small for gestational age who fail to catch up in growth.

Approved Indications in Adults

  • Adult-onset or childhood-onset GHD.

  • HIV/AIDS–associated wasting syndrome.

  • Short bowel syndrome in combination with dietary management.

Administration and Dosage

  • Recombinant human growth hormone is administered subcutaneously.

  • Dosage is individualized based on age, diagnosis, body weight, and treatment goals.

  • Pediatric doses are generally higher per kilogram of body weight than adult doses.

  • Therapy is monitored through growth velocity (in children), IGF-1 levels, body composition changes, and adverse effects.

Contraindications

  • Active malignancy.

  • Acute critical illness (e.g., following major surgery, trauma, or respiratory failure).

  • Proliferative or severe non-proliferative diabetic retinopathy.

  • Known hypersensitivity to somatropin or any component of the formulation.

Precautions

  • Regular monitoring of IGF-1 to avoid supraphysiologic levels.

  • Caution in patients with a history of cancer due to potential tumor recurrence risk.

  • Dose adjustments may be required in elderly patients or those with glucose intolerance.

  • Monitor for signs of intracranial hypertension, slipped capital femoral epiphysis in children, and scoliosis progression.

Adverse Effects

  • Common: Injection site pain, edema, joint pain, myalgia, paresthesia.

  • Metabolic: Hyperglycemia, insulin resistance, possible progression to type 2 diabetes mellitus.

  • Musculoskeletal: Carpal tunnel syndrome, arthralgia, slipped epiphysis (in children).

  • Cardiovascular: Fluid retention leading to hypertension or edema.

  • Rare: Intracranial hypertension, pancreatitis, gynecomastia.

Drug Interactions

  • Glucocorticoids: Can antagonize GH effects on growth.

  • Insulin and oral hypoglycemics: Dose adjustments may be required due to altered glucose metabolism.

  • Cytochrome P450–metabolized drugs: GH may affect clearance of drugs metabolized by CYP3A4 (e.g., some anticonvulsants, corticosteroids, sex steroids).

  • Estrogen therapy: Oral estrogens can reduce IGF-1 response, sometimes requiring GH dose adjustments.

GH Insensitivity – Laron Syndrome

A rare autosomal recessive disorder caused by mutations in the GH receptor gene, leading to ineffective GH signaling and low IGF-1 levels despite elevated GH concentrations. Clinical features include proportionate short stature, obesity, and characteristic facial features. Treatment involves recombinant IGF-1 (mecasermin) rather than GH.

Misuse and Doping Concerns

HGH is misused by athletes and individuals seeking anti-aging benefits or body enhancement. These uses are not supported by strong scientific evidence and are associated with increased risks of side effects. Its non-medical use is banned in competitive sports, and detection methods in doping control include blood-based assays for GH isoforms and biomarkers.



on

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)