Peptide Hormone

A peptide hormone is a chemical messenger of peptide nature secreted by an endocrine gland, released into the bloodstream, and acting at a distance on target tissues bearing specific receptors. Historically, they are contrasted with steroid hormones (lipid-soluble, membrane-permeable) because their hydrophilic nature forces them to act through membrane receptors.

Structurally, peptide hormones span a broad spectrum: very short peptides (TRH, 3 amino acids), medium polypeptides (insulin, 51 aa in two chains A and B linked by disulfide bridges), and large glycoprotein hormones (follicle-stimulating hormone FSH, luteinizing hormone LH, thyroid-stimulating hormone TSH, hCG, all heterodimeric α/β glycosylated structures). Glycosylation plays a key role in plasma half-life and receptor recognition.

Biosynthesis generally follows the pre-pro-hormone to mature hormone pathway. Insulin illustrates this: preproinsulin is cleaved to proinsulin in the endoplasmic reticulum, and proinsulin loses its C-peptide in secretory granules to form mature insulin. Secretion is regulated by physiological signals (blood glucose, antagonist hormones, autonomic innervation).

Target receptors fall mainly into two families: receptor tyrosine kinases (insulin, IGF-1) and GPCRs (glucagon, GLP-1, GIP, PTH, calcitonin, oxytocin, vasopressin, pituitary hormones). Signal transduction activates intracellular cascades (MAPK, PI3K-Akt, cAMP, PLC, calcium) that converge on metabolic, growth, or behavioral responses.

Their pharmacokinetics are constrained by size and susceptibility to peptidases: short plasma half-life (minutes), fast clearance by liver and kidney, and administration essentially parenteral. Synthetic peptide analogs (semaglutide, tirzepatide, liraglutide, desmopressin) bypass these limits via acylation, PEGylation, or substitution with non-natural amino acids.