Module 3E Notes

Overview of Growth Hormones and Related Compounds

  • Discussion of four key compounds:
    • Growth Hormone
    • Growth Hormone Peptide Releasing Hormones
    • Insulin Like Growth Factor (IGF)
    • Mechanogrowth Factor
  • These compounds are grouped together due to their similar mechanisms of action.

Growth Hormone (GH)

  • Definition: A pleiotropic hormone that stimulates various metabolic processes in cells.

  • Effects on Metabolism:

    • Influences protein, fat, carbohydrate, and mineral metabolism.
    • Associated outcomes:
      • Reductions in body fat.
      • Increases in muscle mass and strength, especially when used with training.
      • Tissue repair in the musculoskeletal system.

  • Clinical Evidence:

    • Minimal evidence supports the effectiveness of growth hormone doping for performance enhancement.

  • Endocrine Axis:

    • GH Insulin Like Growth Factor 1 (IGF-1) axis involves:
      • Growth Hormone Releasing Hormone (GHRH): Stimulates the pituitary gland to release GH.
      • IGF-1: Circulates primarily due to liver stimulation after GH release.
      • Local production of IGF-1 also affects surrounding tissues.
      • Collagen markers: GH impacts binding proteins like collagen and IGFBPs.

  • Clinical Applications:

    • Approved for the following conditions:
      • Growth hormone deficiency
      • Chronic kidney disease (CKD)
      • Turner syndrome
      • Small for gestational age
      • Prader-Willi syndrome
      • Idiopathic short stature
      • Shock's gene halo insufficiency
      • Noonan syndrome
    • Common efficacy outcomes:
      • Increases in linear growth in infants, children, adolescents, and prevention of hypoglycemia in congenital hypopituitarism.

  • Biological Activities:

    • Improves nitrogen retention, enhances amino acid transport to skeletal muscle, promotes growth, elongates growth plates, stimulates IGF-1 and IGFBP-3 production.
    • Influences metabolic processes:
      • Lipolysis stimulation, sodium retention, phosphorus retention, antagonistic effects on insulin, beta cell hyperplasia, stimulated lactogenesis, modulation of immune functions.

  • Diurnal Patterns:

    • Growth hormone secretion has a diurnal rhythm with elevated levels during sleep.
    • Uniquely different patterns observed between males and females, with females experiencing more frequent spikes.

Growth Hormone in Sports

  • Rationale for Doping:

    • Ergogenic effects leading to enhanced performance (master anabolic hormone).
    • Increases skeletal muscle mass, thus enhancing strength and endurance.
    • Improves nutrient assimilation to build muscle and liberates calories from fat, redirecting energy towards muscle growth.
    • Accelerates injury recovery and may aid in weight loss.
    • Historically, undetectable in anti-doping tests; however, detection methods have been revised.

  • Variants and Experimental Compounds:

    • AOD 9604: Anti-obesity drug and growth hormone variant, still in trials, used for fat burning.
    • Administration of specific dosages (22k or 20k growth hormone) leads to suppression of endogenous GH production for up to 12 hours.

  • Dosage Effects:

    • Comparison of low (2.31 mg) versus high (5.81 mg) doses shows higher dosages resulting in a 250% to 350% elevation over baseline, lasting up to 34 hours.

  • Side Effects:

    • 15%-44% of GH users may experience:
      • Edema
      • Arthralgia
      • Carpal tunnel syndrome
      • Increased sweating
      • Sodium and fluid retention
      • Soft tissue swelling
      • Nerve entrapments
      • Joint stiffness
      • Hypertension
      • Peripheral edema
      • Myalgia
      • Insulin resistance
      • Gynecomastia
      • Acromegaly-like changes with prolonged use (bone remodeling, arthritis, cardiovascular changes).
    • A notable sign of GH use: prolonged orthodontic treatment for teeth growth in athletes.

Clinical Research and Findings

  • A 2010 study involving 35 women and 68 men administered GH examined performance effects:

    • Resulted in improved VO₂ max, increased deadlift performance, jump height, and Wingate cycling performance.
    • Notable decreases in fat mass and increases in lean mass.
    • Varied responses among individuals, highlighting different reactions to GH use.

  • Exercise Capacity and Performance:

    • Enhanced plasma lactate levels, heart rate, free fatty acids, and glycerol levels were observed.
    • Results on cycling speed were mixed across studies.
    • Improvements generally noted for maximal inspiratory pressure and VO₂ max.

  • Biomarkers and Detection:

    • Response to GH therapy monitored using IGF-1 and procollagen type III amino terminal peptide (P3NP), indicators for GH doping detection.
    • Notable gender differences in both performance enhancement and biomarker response throughout treatment.

Growth Hormone Releasing Peptides (GHRPs)

  • Definition: Compounds that stimulate the release of endogenously produced GH.

    • Common types include GHRP-6, GHRP-2, and Hexarelin.
    • Approved in competition but frequently used in sports like CrossFit and bodybuilding.

  • Mechanism of Action:

    • Stimulate the hypothalamus to enhance somatotropin secretion.
    • Effects are shown to be dose-dependent; higher doses yield greater GH release.

  • Studies on GHRP Efficacy:

    • Research indicates substantial increases in GH secretion rates during infusions.
    • GHRP effects on newborns demonstrated significant stimulation of GH release.

  • Detection:

    • GHRPs can be detected in urine, with established detection limits facilitating identification for anti-doping measures.

Insulin Like Growth Factor 1 (IGF-1)

  • Definition: A hormone critical for cell growth, secreted by the liver, primarily stimulated by GH.

  • Mechanisms of Action:

    • Acts through the IGF-1 receptor in various regulatory manners (autocrine, paracrine, classical endocrine).
    • Circulating IGF-1 binds to high-affinity IGF binding proteins (IGFBPs) which modulate its biological actions.
    • Negative feedback mechanism whereby excess IGF-1 reduces its own production.

  • Synergistic Activity:

    • GH and IGF-1 cooperate synergistically with insulin in the regulation of protein synthesis and anabolic processes.
    • The anabolic effects require presence of insulin to manifest fully.

Mechanogrowth Factor (MGF)

  • Role in Tissue Repair:

    • Stimulated by mechanical signals (e.g., local cell damage) and is involved in tissue repair processes.
    • Increased expression of MGF observed with recombinant GH in elderly with GH deficiency.

  • Applications and Bans:

    • Usage in sports (notably bodybuilding) and is prohibited in competition due to performance-enhancing effects.