A regulatory mechanism in which the product of a biological process inhibits further production of that product, maintaining homeostasis. The classic example is the hypothalamic-pituitary-adrenal (HPA) axis: cortisol released by the adrenals acts back on the hypothalamus and pituitary to suppress further cortisol-stimulating signals.

Negative feedback is critical for understanding peptide pharmacology. Exogenous growth hormone suppresses natural GH production via negative feedback on the pituitary—which is why GH secretagogues (which stimulate endogenous production) are pharmacologically distinct from GH replacement. GnRH agonists like leuprolide exploit negative feedback: continuous stimulation paradoxically suppresses the reproductive axis by overriding the pulsatile pattern the system requires. Understanding feedback loops is essential for evaluating claims about peptide cycling, receptor desensitization, and the long-term consequences of chronic peptide use.