Hormonal Regulation

Hormonal Regulation of Metabolism

Hormones are chemical messengers that coordinate metabolic responses across different tissues. They act through specific receptors and second messenger systems to regulate enzyme activity and gene expression.

Classification by Mechanism

  • Peptide / Protein Hormones (water-soluble): Cannot enter cells. Act through cell surface receptors → second messengers (cAMP, IP3, DAG, Ca²⁺). Rapid response (seconds-minutes). Examples: Insulin, Glucagon, GH, PTH, TSH, ACTH, Epinephrine (also a monoamine).
  • Steroid Hormones (lipid-soluble): Enter cells → cytoplasmic or nuclear receptors → receptor-hormone complex → binds HRE (hormone response elements) on DNA → transcription changes. Slower response (hours). Examples: Cortisol, Aldosterone, Estrogen, Testosterone, Progesterone, Vitamin D.
  • Thyroid Hormones (T3/T4): Act like steroids (nuclear receptors) despite being amino acid derivatives. Regulate basal metabolic rate.

Second Messenger Systems

  • cAMP pathway: Hormone → Gs-coupled GPCR → Adenylyl Cyclase → ↑cAMP → Protein Kinase A (PKA) → phosphorylates multiple targets. Used by: Glucagon, Epinephrine, PTH (Gs), TSH, ACTH, FSH, LH.
  • IP3/DAG pathway: Hormone → Gq-coupled GPCR → Phospholipase Cβ → PIP2 → IP3 (→ Ca²⁺ release from ER) + DAG (→ PKC activation). Used by: Angiotensin II, Epinephrine (α1), Histamine (H1), TRH, GnRH, Oxytocin, ADH (V1).
  • Tyrosine Kinase Receptors (RTKs): Hormone → dimerization → autophosphorylation → RAS/MAP kinase cascade (growth, differentiation) or PI3K/AKT (metabolism, survival). Used by: Insulin, IGF-1, EGF, PDGF, FGF.
  • Insulin Signaling: Insulin → IR (RTK) → IRS-1 → PI3K → PIP3 → PDK1 → AKT. AKT: ↑GLUT4 translocation, ↑Glycogen synthesis (phosphorylates GSK-3 → inactive → dephosphorylates GS → active), ↑FA synthesis, ↓Gluconeogenesis (↓FOXO), ↑Protein synthesis (mTOR).

Key Metabolic Hormones

  • Insulin: Anabolic; lowers blood glucose. Released by glucose (and GLP-1 from gut). C-peptide released equimolarly — marker of endogenous insulin production.
  • Glucagon: Catabolic; raises blood glucose. Alpha cells. Activates PKA via cAMP in liver.
  • Cortisol: Stress hormone; catabolic. ↑Gluconeogenesis, ↑Proteolysis, ↑Lipolysis, ↓Glucose uptake (insulin resistance), ↑Blood glucose ("steroid diabetes"). Anti-inflammatory.
  • Epinephrine: Acute stress; β-1 → ↑heart rate; β-2 → vasodilation/bronchodilation; β-2 → ↑glycogenolysis; α-1 → vasoconstriction.
  • Thyroid Hormones (T3): ↑BMR, ↑Na/K ATPase, ↑Fat oxidation, ↑Cardiac output. Hyperthyroidism → weight loss, tachycardia, heat intolerance.
  • Leptin: Adipokine; signals satiety to hypothalamus; deficiency → severe obesity (ob/ob mice).
  • Adiponectin: Anti-inflammatory; ↑insulin sensitivity; ↑FA oxidation via AMPK; low in obesity/T2DM.

Hormonal Control of Blood Glucose (Summary)

↓Blood glucose → ↑Glucagon, ↑Epinephrine, ↑GH, ↑Cortisol → counter-regulatory → ↑glucose

↑Blood glucose → ↑Insulin → ↑Glucose uptake, ↑Glycogenesis, ↑Lipogenesis → ↓glucose