Week 3

• Regulation of HGH production involves feedback mechanisms in response to stress, exercise, nutrition, sleep, and HGH itself
• Growth hormone-releasing hormone (GHRH) promotes HGH production and release, while somatostatin inhibits GHRH release and HGH response to GHRH stimulus
• Human growth hormone (HGH), also known as somatotropin, is a 191 amino acid single-chain polypeptide produced by somatotropic cells within the anterior pituitary gland.
• HGH is produced in the anterior pituitary of the brain in somatotrophic cells

  
  

  HGH is responsible for growth regulation during childhood and the regulation of many of the body's other basal metabolic functions.
• Ghrelin, produced in the gastrointestinal tract, stimulates HGH secretion when elevated
• Insulin-like growth factor-1 inhibits HGH release and increases somatostatin release
• HGH negatively feeds back into the hypothalamus, decreasing GHRH production
• HGH has direct and indirect effects on the body, with indirect effects mediated by insulin-like growth factor-1
• HGH impacts metabolism by up-regulating insulin-like growth factor-1 production and affecting basal metabolic functions of organ tissues
• HGH promotes anabolic protein state, triglyceride breakdown, gluconeogenesis, and overall hyperglycemia
• HGH stimulation tests involve fasting overnight and administering a pharmacological challenge in the morning to evaluate HGH serum levels.
• Acromegaly is caused by an HGH-secreting pituitary adenoma and primarily affects flat bones, resulting in symptoms such as swelling of the hands and head.
• Gigantism is similar to acromegaly but occurs when the pituitary adenoma develops before the closure of long bone epiphysis, leading to bone growth in long bones.
• HGH deficiency in children is often idiopathic, while in adults it is typically associated with hypopituitary deficiencies.
• Adult-onset HGH deficiency is characterized by decreased skeletal muscle, increased fat mass, decreased bone density, dyslipidemia, insulin resistance, and secondary cardiovascular dysfunction.
• GH is secreted by somatotroph cells in the anterior pituitary gland.
• GH secretion occurs in a pulsatile fashion and has a circadian rhythm, with maximum release during the second half of the night.
• GH secretion is gender, pubertal status, and age dependent.

  
  

  Sleep is an important physiological factor that increases GH release.
• GH synthesis and secretion are stimulated by growth hormone-releasing hormone (GHRH) and inhibited by somatostatin (SST).
• GH stimulates IGF-I production, which in turn inhibits GH secretion at both hypothalamic and pituitary levels.
• Ghrelin, a gastric peptide, is a potent GH secretagogue that amplifies GHRH secretion and synergizes with its GH-stimulating effects.
• Estrogens stimulate GH secretion but inhibit its action on the liver by suppressing GH receptor signaling.
• Androgens enhance the peripheral actions of GH.
• GHRH (Growth Hormone-Releasing Hormone): Stimulates GH transcription and secretion, plays a role in somatotroph proliferation, and is inhibited by SST, IGF-I, and activation of GABAergic neurons.
• GHRH Receptor Mutations lead to profound GH deficiency and anterior pituitary hypoplasia, but lack typical features of GH deficiency.
• Age-Associated Changes in GH: Decreased GH levels may be related to senescent changes in body composition, but the cause-effect relationship is unknown. Intra-abdominal fat mass is a negative predictor of peak GH levels.
• IGF-I declined with age but showed no significant association with body composition or physical performance
• GH treatment has gender differences, with men being more responsive in terms of IGF-I generation and fat loss
• High insulin levels suppress IGFBP-1, leading to a relative increase in free IGF-I levels
• Systemic elevations of FFA, insulin, and free IGF-I suppress pituitary GH release, further increasing fat mass
• Patients with life-long severe reduction in GH signaling show central obesity, insulin sensitivity, and reduced cancer risk
• GH may possess immunomodulatory actions and stimulate T and B-cell proliferation and immunoglobulin synthesis.
• GHRs have been identified in many tissues including fat, lymphocytes, liver, muscle, heart, kidney, brain, and pancreas.
• GH and insulin may compete for intracellular substrates, explaining the negative effect of GH on insulin signaling.
• SOCS proteins negatively regulate the insulin signaling pathway.
• GH stimulates synthesis of IGF-I in the liver and other tissues.
• IGF-I receptor is expressed in many tissues and its activation leads to cell growth.

  
  

  IGF-I is a global and tissue-specific growth factor and acts as an endocrine factor.
• GH stimulates lipolysis in a state of decreased nutrient intake, during sleep, and exercise.
• Infusion of high-dose GH in healthy adults reduces glucose uptake and increases uptake and oxidation of FFA.
• GH and insulin have opposite metabolic actions in terms of glucose and fatty acid uptake and oxidation.