Secretagogue

A secretagogue acts on the machinery of secretion rather than replacing its product. It binds a receptor on a secretory cell and triggers the events — usually calcium entry and vesicle fusion — that release stored or newly made hormone. The defining consequence is dependence on the host: the effect needs an intact cell population, an available pool, and the feedback loops that govern the axis remain in place.

Sulfonylureas are insulin secretagogues that close the beta-cell KATP channel through SUR1, releasing insulin regardless of prevailing glucose, which is why hypoglycaemia is their characteristic hazard; incretin-based agents release insulin only when glucose is elevated. In the growth hormone axis, releasing peptides and ghrelin mimetics act at GHS-R1a on the pituitary somatotroph. Macimorelin, an oral ghrelin receptor agonist, was approved by the FDA in 2017 as a diagnostic for adult GH deficiency.

The upstream position cuts both ways. Because release passes through the normal secretory apparatus, the pattern retains physiological structure and negative feedback still applies, capping the effect near what the gland can produce — a real difference from exogenous hormone, which overrides the axis and suppresses it. The same dependence means a secretagogue does nothing where the gland has failed.

The inference to resist is that upstream means safe or physiological by definition. Repeated stimulation desensitises the receptor and blunts later responses, ghrelin receptor agonists stimulate appetite and can worsen insulin sensitivity, and growth hormone secretagogues sit on the WADA prohibited list alongside growth hormone itself. Secretagogue describes where a compound acts, not how benign it is.