Hormones

Mr. Arvind Kumar

Introduction

  • The term hormone comes from the Greek word hormao, meaning “to excite” or “to set in motion.”
  • Hormones play a central role in communication within the body by transmitting signals between organs and tissues.
  • They are secreted in very small amounts but have profound effects on body functions.
  • Depending on their chemical nature, hormones can be peptides, steroids, amino acid derivatives, or fatty acid derivatives.

  • Unlike neurotransmitters, which act locally and rapidly, hormones usually act more slowly but produce long-lasting effects.
  • Their actions are mediated through specific receptors, either on the surface of target cells or within the cell nucleus, thereby regulating biochemical pathways, gene expression, and overall body homeostasis.

 

History of Hormones

  • 1838 – Berthold: First endocrine experiment on roosters → testes secrete a substance (testosterone).

  • 1855 – Addison: Described adrenal insufficiency (Addison’s disease).

  • 1901 – Takamine: Isolated adrenaline (epinephrine).

  • 1902 – Bayliss & Starling: Discovered secretin, the first hormone.

  • 1905 – Starling: Coined the term “hormone.”

  • 1921 – Banting & Best: Discovered insulin → treatment of diabetes.

  • 1930s–50s: Steroid hormones (estrogen, progesterone, cortisol) identified.

  • 1959 – Yalow: Developed radioimmunoassay (RIA) to measure hormones.

  • Modern era: Recombinant DNA → synthetic hormones (insulin, GH); discovery of hypothalamic hormones and hormone receptors.

 

Classification 

Hormones can be classified in several ways, depending on their chemical nature, solubility, or mechanism of action.

1. Based on Chemical Nature

  1. Peptide and Protein Hormones

    • Made up of chains of amino acids (short = peptide; long = protein).

    • Water-soluble, cannot cross cell membranes directly.

    • Act via cell surface receptors and second messengers.

    • Examples:

      • Peptide hormones: ADH (Vasopressin), Oxytocin, Glucagon.

      • Protein hormones: Insulin, Growth Hormone (GH), Prolactin.

  2. Steroid Hormones

    • Derived from cholesterol.

    • Lipid-soluble, easily cross the plasma membrane.

    • Act via intracellular receptors (cytoplasmic/nuclear).

    • Examples: Cortisol, Aldosterone, Estrogen, Testosterone, Progesterone.

  3. Amino Acid Derivatives

    • Derived from single amino acids (mainly tyrosine or tryptophan).

    • May be water-soluble or lipid-soluble.

    • Examples:

      • From tyrosine: Thyroxine (T4), Triiodothyronine (T3), Epinephrine, Norepinephrine, Dopamine.

      • From tryptophan: Melatonin, Serotonin.

  4. Fatty Acid Derivatives (Eicosanoids)

    • Derived from arachidonic acid.

    • Mostly act locally (paracrine/autocrine action).

    • Examples: Prostaglandins, Leukotrienes, Thromboxanes.

 

2. Based on Solubility

  1. Water-Soluble Hormones

    • Cannot cross the lipid bilayer; bind to membrane receptors.

    • Usually act rapidly through second messengers.

    • Examples: Peptide/protein hormones (Insulin, Glucagon, ACTH), Catecholamines (Epinephrine, Norepinephrine).

  2. Lipid-Soluble Hormones

    • Can diffuse across the plasma membrane.

    • Bind to intracellular receptors and regulate gene expression.

    • Act slowly but effects are long-lasting.

    • Examples: Steroid hormones (Cortisol, Testosterone), Thyroid hormones (T3, T4), Calcitriol.

 

3. Based on Mechanism of Action (Group I & Group II)

  1. Group I Hormones (Intracellular receptor-mediated)

    • Lipid-soluble, act via intracellular (cytoplasmic or nuclear) receptors.

    • Regulate transcription and protein synthesis.

    • Examples: Steroid hormones (Cortisol, Aldosterone, Estrogen, Testosterone, Progesterone), Thyroid hormones (T3, T4), Calcitriol.

  2. Group II Hormones (Membrane receptor mediated)

    • Water-soluble, act via membrane-bound receptors.

    • Use second messengers (cAMP, cGMP, IP3, DAG, Ca²⁺).

    • Examples:

      • cAMP mediated: Glucagon, ACTH, TSH, FSH, LH, Epinephrine (β-receptors).

      • cGMP mediated: ANP, Nitric oxide.

      • IP3/DAG mediated: ADH (via V1 receptor), Oxytocin, Epinephrine (α1-receptors).

      • Tyrosine kinase mediated: Insulin, IGF-1, Growth hormone.

 

4. Based on Source of Secretion

  1. Pituitary hormones: GH, TSH, ACTH, LH, FSH, Prolactin, ADH, Oxytocin.

  2. Thyroid hormones: T3, T4, Calcitonin.

  3. Parathyroid hormone: Parathormone (PTH).

  4. Adrenal hormones: Cortisol, Aldosterone, Epinephrine, Norepinephrine.

  5. Pancreatic hormones: Insulin, Glucagon, Somatostatin.

  6. Gonadal hormones: Testosterone, Estrogen, Progesterone, Inhibin.

  7. Other sources: Melatonin (pineal gland), Erythropoietin (kidney), Calcitriol (kidney), Gastrin/Secretin/Cholecystokinin (GI tract).

 

Mechanism of Action of Group I Hormones

  • Group I hormones are lipid-soluble hormones (mainly steroid and thyroid hormones, along with calcitriol).

  • Because of their lipophilic nature, they easily diffuse through the plasma membrane and act through intracellular receptors (cytoplasmic or nuclear).

  • Their main mode of action is to alter gene expression and regulate the synthesis of specific proteins/enzymes.

  • Effects are slow in onset (hours to days) but long-lasting compared to Group II hormones.

Examples of Group I Hormones

  • Steroid hormones: Cortisol, Aldosterone, Estrogen, Progesterone, Testosterone.

  • Thyroid hormones: Triiodothyronine (T3), Thyroxine (T4).

  • Vitamin D derivative: Calcitriol (1,25-dihydroxycholecalciferol).

Steps in Mechanism of Action

  1. Transport in Blood

    • Lipophilic hormones are mostly transported bound to plasma proteins (e.g., Cortisol-binding globulin, Thyroxine-binding globulin).

    • Only the free, unbound fraction is biologically active.

  2. Entry into Target Cell

    • Free hormone diffuses across the lipid bilayer of the cell membrane due to its lipophilic nature.

  3. Binding to Intracellular Receptor

    • Hormone binds to a specific intracellular receptor, either in the cytoplasm (e.g., steroid receptors for cortisol, aldosterone) or nucleus (e.g., thyroid hormone receptors).

    • Binding causes conformational change in the receptor, often releasing inhibitory proteins (like heat-shock proteins).

  4. Formation of Hormone–Receptor Complex

    • The activated hormone–receptor complex is formed.

    • This complex is capable of binding DNA.

  5. Translocation to Nucleus (for cytoplasmic receptors)

    • If the receptor is cytoplasmic, the complex translocates to the nucleus.

    • Nuclear receptors (e.g., for thyroid hormones) are already located inside the nucleus.

  6. Binding to DNA (Hormone Response Elements – HREs)

    • The complex binds to specific DNA sequences called Hormone Response Elements (HREs) located in the promoter region of target genes.

  7. Regulation of Gene Transcription

    • The hormone–receptor complex acts as a transcription factor, either activating or repressing transcription of specific genes.

    • This leads to increased or decreased production of messenger RNA (mRNA).

  8. Protein Synthesis

    • mRNA is translated by ribosomes to form new proteins or enzymes.

    • These proteins bring about the biological effects of the hormone.

Group I Hormone Action

  • Receptors: Intracellular (cytoplasm or nucleus).

  • Second messengers: Not required.

  • Action: Direct regulation of gene expression.

  • Speed: Slow onset, but long duration.

  • Outcome: Synthesis of new proteins/enzymes → physiological response.

 

Mechanism of Action of Group II Hormones

  • Group II hormones are water-soluble hormones.

  • They cannot cross the lipid bilayer of the cell membrane.

  • They act by binding to cell surface (membrane-bound) receptors.

  • Their effects are mediated through second messenger systems inside the cell.

  • Action is rapid in onset but usually short-lasting compared to Group I hormones.

Examples of Group II Hormones

  • Peptide/Protein hormones: Insulin, Glucagon, Parathyroid hormone (PTH), ACTH, TSH, FSH, LH.

  • Catecholamines: Epinephrine, Norepinephrine (except thyroid hormones which are Group I).

  • Others: ADH, Oxytocin, ANP.

Mechanism of Action of Group II Hormones

Since they cannot enter the cell, they act via cell surface receptors linked to second messengers.

There are four major pathways:

1. cAMP Pathway (Adenylate Cyclase Pathway)

  • Hormone binds to receptor → activates Gs protein → stimulates adenylate cyclase → ↑ cAMP.

  • cAMP activates protein kinase A (PKA) → phosphorylation of target proteins → physiological effects.

  • Examples: Glucagon, ACTH, TSH, FSH, LH, Epinephrine (β-receptors).

2. cGMP Pathway

  • Hormone binds receptor → activates guanylate cyclase → ↑ cGMP.

  • cGMP activates protein kinase G (PKG) → relaxation/other cellular responses.

  • Examples: Atrial Natriuretic Peptide (ANP), Nitric oxide (NO).

3. IP3–DAG Pathway (Phospholipase C Pathway)

  • Hormone binds receptor → activates Gq protein → stimulates phospholipase C (PLC).

  • PLC hydrolyzes PIP2 into IP3 and DAG.

    • IP3 → releases Ca²⁺ from endoplasmic reticulum.

    • DAG + Ca²⁺ → activate protein kinase C (PKC).

  • This leads to phosphorylation of proteins and cellular effects.

  • Examples: ADH (via V1 receptor), Oxytocin, Epinephrine (α1-receptors), Angiotensin II.

4. Tyrosine Kinase Pathway

  • Hormone binds to receptor with intrinsic tyrosine kinase activity.

  • Causes autophosphorylation of receptor → activates signaling cascades (MAP kinase, PI3K pathways).

  • Results in protein synthesis, growth, metabolic regulation.

  • Examples: Insulin, IGF-1, Growth hormone, Prolactin.

Features of Group II Hormones

  • Receptors: On plasma membrane.

  • Second messengers: cAMP, cGMP, IP3, DAG, Ca²⁺, Tyrosine kinase signaling.

  • Action: Rapid and short-lasting.

  • Speed: Very fast (seconds to minutes).

  • Outcome: Activation/inhibition of enzymes, opening of ion channels, rapid metabolic effects.

 

Comparison: Group I vs Group II

Feature Group I Group II
Solubility Lipid-soluble Water-soluble
Receptor location Intracellular (cytoplasm/nucleus) Cell surface (membrane)
Mediator Direct gene regulation Second messengers
Onset Slow (hours to days) Rapid (seconds to minutes)
Duration Long-lasting Short-lasting
Examples Steroid, Thyroid hormones, Calcitriol Insulin, Glucagon, Catecholamines, Peptide hormones

 

Functions of Hormones

Hormones regulate almost every physiological process in the body. Their functions can be grouped as follows:

1. Regulation of Growth and Development

  • Control the growth of bones, muscles, and tissues.

  • Influence sexual maturation and differentiation.

  • Examples:

    • Growth Hormone (GH) – stimulates overall body growth.

    • Thyroid Hormones (T3, T4) – essential for brain and skeletal development.

    • Sex hormones (Estrogen, Testosterone) – regulate puberty and secondary sexual characteristics.

2. Regulation of Metabolism and Energy Balance

  • Maintain energy production, storage, and utilization.

  • Influence carbohydrate, protein, and fat metabolism.

  • Examples:

    • Insulin – promotes glucose uptake and storage.

    • Glucagon – increases blood glucose by glycogen breakdown.

    • Thyroid hormones – increase basal metabolic rate.

    • Cortisol – stimulates gluconeogenesis and protein catabolism.

3. Maintenance of Homeostasis (Internal Balance)

  • Help maintain stable internal environment despite external changes.

  • Examples:

    • Aldosterone – regulates sodium and potassium balance.

    • ADH (Vasopressin) – conserves water in kidneys.

    • PTH and Calcitonin – regulate calcium and phosphate levels.

    • Insulin and Glucagon – maintain blood glucose balance.

4. Regulation of Reproduction and Sexual Functions

  • Control development of reproductive organs and fertility.

  • Maintain menstrual cycle, pregnancy, and lactation.

  • Examples:

    • Estrogen and Progesterone – regulate menstrual cycle and pregnancy.

    • Testosterone – regulates sperm production and male sexual functions.

    • Prolactin – stimulates milk production.

    • Oxytocin – aids in childbirth and milk ejection.

5. Adaptation to Stress and Emergency (Fight-or-Flight Response)

  • Enable the body to respond quickly to stress, danger, or injury.

  • Examples:

    • Epinephrine & Norepinephrine – increase heart rate, blood pressure, and energy mobilization.

    • Cortisol – helps body adapt to prolonged stress by mobilizing energy reserves.

6. Regulation of Mood, Behavior, and Biological Rhythms

  • Influence emotions, mental health, sleep, and circadian rhythms.

  • Examples:

    • Melatonin – regulates sleep–wake cycle.

    • Serotonin – affects mood and emotional balance.

    • Cortisol – has diurnal rhythm (high in morning, low at night).

7. Control of the Immune System and Inflammation

  • Some hormones regulate immunity and inflammatory processes.

  • Examples:

    • Cortisol – suppresses inflammation and immune responses.

    • Thymosin – regulates T-cell development.