Properties

The physical and chemical properties of hormones influence their synthesis, transport, receptor binding, and mechanism of action

Steroid Hormones

Examples: Cortisol, aldosterone, testosterone, estradiol (estrogen), progesterone, hCG
Source: Adrenal cortex, gonads, placenta
Biochemical Theory and Pathway
- Synthesis: Steroid hormones are synthesized from cholesterol through a series of enzymatic reactions
- Key Enzymes: Cytochrome P450 enzymes (CYP enzymes) are involved in many steps of steroid hormone synthesis
- Synthesis Pathway
  - Cholesterol is converted to pregnenolone by CYP11A1 (cholesterol side-chain cleavage enzyme)
  - Pregnenolone is converted to various steroid hormones through different pathways in different tissues
  - Cortisol: Synthesized in the adrenal cortex
  - Aldosterone: Synthesized in the adrenal cortex
  - Testosterone: Synthesized in the testes
  - Estradiol: Synthesized in the ovaries
  - Progesterone: Synthesized in the ovaries and placenta
Physical Properties
- Structure: Characterized by a four-ring structure (steroid nucleus)
- Solubility: Lipid-soluble
  - Hydrophobic and poorly soluble in water
  - Transported in the bloodstream bound to carrier proteins
- Molecular Weight: Relatively low (250-400 Da)
Chemical Properties
- Stability: Relatively stable due to their ring structure
- Reactivity: Undergo enzymatic modifications (e.g., hydroxylation, oxidation, reduction)
  - These modifications can alter their biological activity
- Polarity: Nonpolar
  - Can diffuse across cell membranes
- Binding Affinity: Bind with high affinity to intracellular receptors

Peptide Hormones

Examples: Insulin, glucagon, growth hormone, prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), parathyroid hormone (PTH), human chorionic gonadotropin (hCG)
Source: Pituitary gland, pancreas, parathyroid gland, placenta
Biochemical Theory and Pathway
- Synthesis: Peptide hormones are synthesized as preprohormones, which are processed to prohormones and then to active hormones
- Translation: Synthesized on ribosomes in the endoplasmic reticulum
- Processing: Undergo post-translational modifications (e.g., glycosylation, cleavage)
  - Cleavage of signal peptides and prohormone sequences
- Storage: Stored in secretory granules
- Secretion: Released by exocytosis in response to appropriate stimuli
Physical Properties
- Structure: Consist of amino acid chains
  - Can be small peptides (e.g., TRH) or large proteins (e.g., GH)
- Solubility: Water-soluble
  - Hydrophilic and readily soluble in water
  - Transported in the bloodstream freely or bound to carrier proteins
- Molecular Weight: Variable, ranging from hundreds to tens of thousands of Daltons
Chemical Properties
- Stability: Less stable than steroid hormones
  - Susceptible to degradation by peptidases
- Reactivity: Undergo glycosylation and other post-translational modifications
  - These modifications can affect their biological activity and stability
- Polarity: Polar
  - Cannot easily diffuse across cell membranes
- Binding Affinity: Bind with high affinity to cell surface receptors

Thyroid Hormones

Examples: Thyroxine (T4), triiodothyronine (T3)
Source: Thyroid gland
Biochemical Theory and Pathway
- Synthesis: Thyroid hormones are synthesized from tyrosine and iodine in the thyroid gland
- Iodide Uptake: Iodide is actively transported into thyroid follicular cells
- Thyroglobulin Synthesis: Thyroglobulin is synthesized in thyroid follicular cells
- Iodination: Iodide is oxidized and attached to tyrosine residues on thyroglobulin
  - Monoiodotyrosine (MIT) and diiodotyrosine (DIT) are formed
- Coupling: MIT and DIT molecules are coupled to form T3 and T4
  - DIT + DIT = T4 (thyroxine)
  - MIT + DIT = T3 (triiodothyronine)
- Storage: T3 and T4 are stored in thyroglobulin within thyroid follicles
- Release: T3 and T4 are released from thyroglobulin by proteolysis and secreted into the bloodstream
- Conversion: T4 is converted to T3 in peripheral tissues by deiodinases
Physical Properties
- Structure: Modified amino acids
  - Contain iodine atoms
- Solubility: Lipid-soluble
  - Transported in the bloodstream bound to thyroxine-binding globulin (TBG) and other carrier proteins
- Molecular Weight: ~650 Da
Chemical Properties
- Stability: Relatively stable
- Reactivity: Can be deiodinated in peripheral tissues
  - T4 is converted to T3 (more active) or reverse T3 (inactive)
- Polarity: Amphipathic
  - Can cross cell membranes but bind to intracellular receptors
- Binding Affinity: Bind with high affinity to intracellular receptors

Catecholamines

Examples: Epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine
Source: Adrenal medulla, sympathetic nervous system
Biochemical Theory and Pathway
- Synthesis: Catecholamines are synthesized from tyrosine in the adrenal medulla and sympathetic neurons
- Tyrosine Hydroxylation: Tyrosine is converted to L-DOPA by tyrosine hydroxylase
- DOPA Decarboxylation: L-DOPA is converted to dopamine by DOPA decarboxylase
- Dopamine Hydroxylation: Dopamine is converted to norepinephrine by dopamine beta-hydroxylase
- Norepinephrine Methylation: Norepinephrine is converted to epinephrine by phenylethanolamine N-methyltransferase (PNMT)
- Storage: Catecholamines are stored in vesicles
- Release: Released by exocytosis in response to neural stimuli
- Metabolism: Metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
Physical Properties
- Structure: Derived from the amino acid tyrosine
  - Contain a catechol ring and an amine group
- Solubility: Water-soluble
  - Hydrophilic and readily soluble in water
  - Transported in the bloodstream freely or bound to carrier proteins
- Molecular Weight: Relatively low (150-200 Da)
Chemical Properties
- Stability: Relatively unstable
  - Susceptible to oxidation and degradation
- Reactivity: Undergo methylation and oxidation
  - Metabolized by MAO and COMT
- Polarity: Polar
  - Cannot easily diffuse across cell membranes
- Binding Affinity: Bind with high affinity to cell surface receptors (adrenergic receptors)

Summary Table of Physical and Chemical Properties

Hormone Category	Solubility	Receptor Location	Primary Transport	Example
Steroid	Lipid-soluble	Intracellular	Carrier Proteins	Cortisol
Peptide	Water-soluble	Cell Surface	Free or Carriers	Insulin
Thyroid	Lipid-soluble	Intracellular	TBG	T3
Catecholamine	Water-soluble	Cell Surface	Free or Carriers	Epinephrine

Clinical Significance

Drug Development: Understanding the physical and chemical properties of hormones is crucial for developing drugs that mimic or block their actions
Assay Development: The properties of hormones influence the design of assays to measure their levels
Hormone Replacement Therapy: Hormone replacement therapy involves administering hormones with specific physical and chemical properties to treat hormone deficiencies

Key Terms

Steroid Hormone: A hormone derived from cholesterol
Peptide Hormone: A hormone composed of amino acids
Thyroid Hormone: A hormone derived from tyrosine and iodine
Catecholamine: A hormone derived from tyrosine, including epinephrine, norepinephrine, and dopamine
Hydrophobic: Water-repelling
Hydrophilic: Water-attracting
Polarity: The distribution of electrical charge in a molecule
Carrier Protein: A protein that binds to and transports hormones in the bloodstream
Receptor: A protein that binds to a specific hormone, initiating a cellular response
Intracellular Receptor: A receptor located within the cell
Cell Surface Receptor: A receptor located on the cell membrane
Half-Life: The time it takes for half of a substance to be eliminated from the body

Action Mechanism

Procedures