Biochemicals

This overview summarizes the key aspects of endocrinology related to biochemical theory and pathways, providing a foundation for understanding hormone function and associated disorders

Biochemical Theory and Metabolic Pathways

• Hormones as Regulators: Hormones are chemical messengers that regulate metabolic pathways to maintain homeostasis. They influence energy production, storage, and utilization
• Key Hormones
  • Insulin: Lowers blood glucose by promoting glucose uptake, glycogenesis, glycolysis, and lipogenesis. Inhibits gluconeogenesis and lipolysis
  • Glucagon: Raises blood glucose by stimulating glycogenolysis and gluconeogenesis. Promotes lipolysis and ketogenesis
  • Epinephrine: Raises blood glucose by stimulating glycogenolysis and gluconeogenesis. Promotes lipolysis and inhibits insulin secretion
  • Cortisol: Raises blood glucose by stimulating gluconeogenesis and protein catabolism. Promotes lipolysis and induces insulin resistance
  • Growth Hormone: Promotes protein synthesis and lipolysis. Induces insulin resistance and stimulates gluconeogenesis
  • Thyroid Hormones: Increase basal metabolic rate, enhance glucose absorption, and affect carbohydrate, lipid, and protein metabolism
• Hormonal Interactions: Hormones often work in opposition to maintain metabolic homeostasis. Their effects are coordinated through complex feedback mechanisms

ormal and Abnormal States

• Normal Endocrine Function
  • Synthesis and Secretion: Hormones are synthesized and secreted in endocrine glands, regulated by feedback mechanisms, neural signals, and hormonal signals
  • Transport: Hormones are transported in the bloodstream, either bound to carrier proteins or freely
  • Action: Hormones bind to specific receptors on target cells, initiating intracellular signaling cascades
  • Metabolism and Excretion: Hormones are metabolized in the liver and kidneys and excreted in the urine or bile
• Abnormal Endocrine Function
  • Hormone Excess: Can be caused by tumors, autoimmune disorders, or ectopic hormone production, leading to exaggerated physiological responses
  • Hormone Deficiency: Can be caused by autoimmune destruction, surgical removal, or genetic defects, leading to impaired physiological responses
  • Receptor Abnormalities: Receptor resistance or mutations can disrupt hormone signaling
• Specific Endocrine Disorders
  • Pituitary Disorders: Acromegaly, Cushing’s disease, hyperprolactinemia, growth hormone deficiency, adrenal insufficiency, hypothyroidism, hypogonadism
  • Thyroid Disorders: Hyperthyroidism (Graves’ disease), hypothyroidism (Hashimoto’s thyroiditis)
  • Adrenal Disorders: Cushing’s syndrome, Addison’s disease, hyperaldosteronism, pheochromocytoma
  • Pancreatic Disorders: Diabetes mellitus (Type 1 & 2), insulinoma
  • Parathyroid Disorders: Hyperparathyroidism, hypoparathyroidism
  • Gonadal Disorders: Hypogonadism, polycystic ovary syndrome (PCOS)

Mechanism of Action

• Hormone Receptors
  • Cell Surface Receptors: Bind to peptide hormones and catecholamines, activating G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), or cytokine receptors
  • Intracellular Receptors: Bind to steroid hormones and thyroid hormones, regulating gene transcription as nuclear receptors
• Signaling Pathways
  • GPCRs: Activate G proteins, leading to changes in cAMP, IP3, and DAG levels
  • RTKs: Undergo autophosphorylation and activate downstream signaling pathways, such as MAPK/ERK and PI3K/Akt
  • Nuclear Receptors: Bind to DNA response elements and recruit coactivators or corepressors to regulate gene transcription
• Cellular Response
  • Hormone signaling leads to changes in enzyme activity, gene expression, and cellular function
• Drug Development
  • Understanding hormone receptor signaling pathways is crucial for developing drugs that target specific hormone-related disorders
  • Agonists activate hormone receptors, while antagonists block hormone receptors

Physical and Chemical Properties

• Steroid Hormones
  • Derived from cholesterol, lipid-soluble, transported by carrier proteins, bind to intracellular receptors
  • Examples: Cortisol, estradiol, testosterone
• Peptide Hormones
  • Composed of amino acid chains, water-soluble, transported freely or by carrier proteins, bind to cell surface receptors
  • Examples: Insulin, glucagon, growth hormone
• Thyroid Hormones
  • Derived from tyrosine and iodine, lipid-soluble, transported by thyroxine-binding globulin (TBG), bind to intracellular receptors
  • Examples: T3, T4
• Catecholamines
  • Derived from tyrosine, water-soluble, transported freely or by carrier proteins, bind to cell surface receptors
  • Examples: Epinephrine, norepinephrine, dopamine
• Impact on Hormone Function
  • The physical and chemical properties of hormones influence their synthesis, transport, receptor binding, and mechanism of action
  • They affect the design of assays to measure their levels and the development of hormone replacement therapies