Secretagogue

A secretagogue is a substance — endogenous, synthetic or peptidic — capable of inducing the secretion of a hormone, neurotransmitter or biological factor by a specialized cell. The term covers a broad pharmacological spectrum and occupies a central place in endocrine and peptide research, notably in studies of regulation pathways for growth hormone, insulin, glucagon and various hypothalamo-pituitary hormones.

Growth hormone secretagogues (GHS) form the most studied family in peptide research. They activate the GHSR-1a receptor (ghrelin receptor) and induce GH release from the anterior pituitary, via a mechanism distinct from GHRH. Natural peptide secretagogues (ghrelin, 28 aa, octanoylated) and synthetic ones (GHRP-2, GHRP-6, hexarelin, ipamorelin) are distinguished from non-peptidic secretagogues (MK-677/ibutamoren, capromorelin, anamorelin).

Other important categories of documented RUO peptide secretagogues: insulin secretagogues (GLP-1, GIP, exendin-4, glucagon paradoxically at physiological dose), glucagon secretagogues (intravenous arginine, certain experimental multi-receptor peptides), hypothalamic secretagogues (GHRH for GH, CRH for ACTH, TRH for TSH, GnRH for LH/FSH), somatostatin secretagogues conversely stimulatory or inhibitory by context.

In experimental pharmacology, secretagogues serve as diagnostic tools (GHRH stimulation test, GHRP-2 test for somatotropic function exploration), fundamental research tools (decrypting intracellular signaling pathways of secretory cells) and therapeutic candidates (treatment of hormonal deficits, cachexia, geriatric anorexia).

The secretagogue notion is closely linked to that of agonist (receptor activator) but differs in focus on the final measurable physiological effect (hormonal release) rather than the molecular receptor mechanism. A peptide can be a weak agonist but a strong secretagogue if downstream amplification is strong.