GHRH

GHRH, or growth hormone-releasing hormone, is a hypothalamic peptide that stimulates the secretion of growth hormone (GH) from the anterior pituitary. In humans, the principal endogenous form is a 44-amino-acid peptide produced mainly in hypothalamic neurons and released into the hypophyseal portal system to act on the pituitary gland.

GHRH binds to the GHRH receptor (GHRHR) on pituitary somatotrophs, activating a Gs protein-coupled signaling pathway that increases cyclic AMP and promotes GH gene transcription and release. GH secretion is pulsatile and tightly regulated by a balance between GHRH stimulation and somatostatin inhibition, with modulation by sleep, nutrition, stress, aging, and ghrelin signaling.

Endogenous GH acts on multiple tissues, particularly the liver, to stimulate the production of IGF-1, which mediates many growth-promoting and metabolic effects. GH and IGF-1 provide negative feedback to reduce GHRH release and pituitary responsiveness. GHRH activity can decline with age and be influenced by physiological states.

Synthetic analogs of GHRH, such as sermorelin, have been used clinically to assess GH deficiency and, in some settings, to treat GH deficiency. These analogs are designed to stimulate GH release with differing pharmacokinetic properties compared with native GHRH. GHRH is distinct from ghrelin and other GH-releasing peptides, which stimulate GH release via different mechanisms. In clinical practice, GHRH stimulation tests help evaluate pituitary function and the integrity of the GH axis.