Classification & Functions
Hormones are chemical messengers produced by endocrine glands and secreted directly into the bloodstream, where they travel to target cells and regulate a vast array of physiological processes. The term 'hormone' derives from the Greek word meaning 'to set in motion,' reflecting their role in initiating, amplifying, or suppressing biological responses. Unlike neurotransmitters, which act over short distances and milliseconds, hormones can travel throughout the entire body and exert effects lasting from seconds to days. From a chemical standpoint, hormones are not a single class of molecule — they span several distinct biochemical families, including steroids (derived from cholesterol), peptides and proteins (chains of amino acids), and amines (derivatives of the amino acid tyrosine or tryptophan). This chemical diversity directly determines how a hormone interacts with its target cell: lipid-soluble steroid hormones can diffuse through the plasma membrane and bind to intracellular receptors, while water-soluble peptide hormones must bind to receptors on the cell surface and trigger second-messenger cascades. Understanding hormone classification and function is central to biomolecular chemistry because hormones exemplify how molecular structure governs biological activity. Disruption of hormonal signalling — through excess, deficiency, or receptor dysfunction — underlies major conditions such as diabetes mellitus, hypothyroidism, Cushing's syndrome, and many reproductive disorders. The study of hormones therefore bridges organic chemistry, biochemistry, and human physiology in a uniquely integrated way.
- Class I — Steroid Hormones
- Class II — Peptide and Protein Hormones
- Class III — Amine Hormones
- Feedback Regulation — Maintaining Homeostasis
- Key Physiological Functions by System
Class I — Steroid Hormones
Steroid hormones are derived biosynthetically from cholesterol (C₂₇H₄₆O) through a series of enzymatic oxidations and side-chain cleavages in the adrenal cortex and gonads. Key examples include cortisol (a glucocorticoid), aldosterone (a mineralocorticoid), testosterone, oestradiol, and progesterone. All share the characteristic four-ring carbon skeleton (three cyclohexane rings fused to one cyclopentane ring). Because they are nonpolar and lipid-soluble, steroid hormones diffuse freely across the phospholipid bilayer. Inside the target cell they bind to specific cytoplasmic or nuclear receptor proteins; the hormone–receptor complex then acts as a transcription factor, binding directly to hormone response elements (HREs) on DNA to up- or down-regulate gene expression. This genomic mechanism produces effects over hours to days — for example, testosterone promotes muscle protein synthesis by increasing transcription of myosin heavy-chain genes.
Class II — Peptide and Protein Hormones
Peptide hormones range from small molecules like thyrotropin-releasing hormone (TRH, a tripeptide: Glu–His–Pro–NH₂) to large glycoproteins like follicle-stimulating hormone (FSH, ~30 kDa). Insulin is a 51-amino-acid protein consisting of an A-chain (21 residues) and a B-chain (30 residues) linked by two disulfide bridges (–S–S–). Because peptide hormones are hydrophilic, they cannot cross the lipid bilayer. Instead, they bind to transmembrane receptor proteins on the cell surface, activating second-messenger systems. For example, glucagon binds its G-protein-coupled receptor (GPCR), activating adenylyl cyclase, which catalyses the conversion of ATP to cyclic AMP (cAMP): ATP → cAMP + PPᵢ. cAMP then activates protein kinase A (PKA), triggering a phosphorylation cascade that mobilises glucose from glycogen within seconds — a non-genomic, rapid response.
Class III — Amine Hormones
Amine hormones are derived from single amino acids. Catecholamines — adrenaline (epinephrine) and noradrenaline (norepinephrine) — are synthesised from tyrosine via a pathway: Tyrosine → DOPA → Dopamine → Noradrenaline → Adrenaline, each step requiring specific enzymes (e.g., tyrosine hydroxylase, DOPA decarboxylase). Structurally they retain the catechol ring (a benzene ring with two adjacent –OH groups) plus an amine side chain. Being water-soluble, catecholamines act via surface receptors (α- and β-adrenergic GPCRs). Thyroid hormones (T₃ and T₄), by contrast, are iodinated derivatives of tyrosine: thyroxine (T₄) contains four iodine atoms and triiodothyronine (T₃) contains three. Despite being derived from an amino acid, thyroid hormones are lipophilic and act like steroid hormones — binding intracellular nuclear receptors and regulating metabolic gene transcription.
Feedback Regulation — Maintaining Homeostasis
Hormone secretion is precisely controlled by feedback loops, most commonly negative feedback. The hypothalamic–pituitary–thyroid (HPT) axis illustrates this clearly: the hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH). TSH acts on the thyroid gland to produce T₃ and T₄. Elevated circulating T₃/T₄ feeds back negatively to inhibit both TRH and TSH release, keeping thyroid hormone levels within a narrow range (free T₄: 9–25 pmol/L in blood). Positive feedback also occurs — for example, the surge of oestradiol just before ovulation triggers a massive LH surge from the pituitary, the only known sustained positive feedback loop in the reproductive axis.
Key Physiological Functions by System
Hormones regulate virtually every organ system: (1) Metabolic regulation — insulin (lowers blood glucose by promoting GLUT4-mediated uptake and glycogen synthesis) and glucagon (raises blood glucose via glycogenolysis and gluconeogenesis) form a pair maintaining blood glucose at 4–6 mmol/L. (2) Growth and development — growth hormone (GH) stimulates IGF-1 production in the liver, promoting cell division and protein synthesis. (3) Reproduction — FSH, LH, oestrogens, progesterone, and testosterone coordinate gametogenesis, the menstrual cycle, pregnancy, and secondary sexual characteristics. (4) Stress response — cortisol mobilises energy substrates, suppresses inflammation, and modulates immune function. (5) Water–electrolyte balance — aldosterone increases Na⁺ reabsorption in the distal tubule of the kidney; ADH (antidiuretic hormone) increases water reabsorption via aquaporin channels.
The Key Equation
- \ce{ATP} — Adenosine triphosphate (mol/L): The universal cellular energy currency; substrate for cAMP synthesis.
- \ce{cAMP} — Cyclic adenosine monophosphate (mol/L): Second messenger that activates protein kinase A, amplifying the hormonal signal inside the cell.
- \ce{PP_{i}} — Inorganic pyrophosphate (mol/L): By-product of cAMP formation; rapidly hydrolysed to 2 Pᵢ, driving the reaction forward.
Worked Example
Problem. A student notes that steroid hormones and thyroid hormones both act via intracellular receptors and regulate gene transcription, yet thyroid hormones are classified as amine hormones derived from tyrosine. Explain why thyroid hormones share the genomic mechanism of steroid hormones despite their different chemical origin, and predict what would happen to plasma TSH levels in a patient with a TSH-secreting pituitary tumour that cannot respond to negative feedback.
Answer. Thyroid hormones act via intracellular receptors because their iodinated, biphenyl-ether structure confers lipophilicity sufficient for membrane diffusion — structure determines mechanism, not amino-acid origin alone. In a feedback-insensitive TSHoma, TSH remains elevated despite high T₃/T₄, driving persistent hyperthyroidism.
Origins · 1 minFrederick Banting and how this was discovered
Frederick Banting, working with Charles Best, John Macleod, and James Collip at the University of Toronto in 1921–1922, isolated insulin from canine pancreatic tissue and demonstrated that injections of the purified extract could lower blood glucose in diabetic dogs and humans. This discovery transformed Type 1 diabetes from a fatal disease into a manageable condition. The team determined that insulin is a protein hormone (later fully sequenced by Frederick Sanger in 1955), establishing a paradigm for peptide hormone research. Banting and Macleod were awarded the Nobel Prize in Physiology or Medicine in 1923 — at the time the fastest Nobel Prize ever awarded after a discovery. Banting was initially an orthopaedic surgeon with no background in endocrinology; his idea to ligate the pancreatic ducts to isolate islet secretions came to him at 2 a.m. after reading a textbook article — he wrote it down in a notebook and it became the starting point for one of medicine's most important discoveries.
Related Concepts
- Enzyme Structure and Function — Many hormones regulate metabolism by activating or inhibiting enzymes through phosphorylation cascades (e.g., insulin activates glycogen synthase); understanding enzyme kinetics and allosteric regulation is essential context for hormone action.
- Protein Structure: Primary to Quaternary — Peptide and protein hormones such as insulin, GH, and FSH are polypeptides whose biological activity depends critically on their three-dimensional folded structure and disulfide bridges.
- Cholesterol and Steroid Biosynthesis — All steroid hormones are synthesised from cholesterol via the mevalonate pathway; understanding the four-ring steroid nucleus and oxidative modifications explains their lipophilicity and receptor binding.
- Amines and Amino Acids — Catecholamine hormones (adrenaline, dopamine) and thyroid hormones are derived from the amino acid tyrosine; knowledge of amine functional groups, pKa, and aromatic substitution explains their synthesis and polarity.
- ATP and Cyclic Nucleotides — The second messenger cAMP, formed from ATP by adenylyl cyclase in peptide hormone signalling, is a cyclic nucleotide whose structure and hydrolysis by phosphodiesterase governs signal duration and amplitude.