A new version of the growth‑hormone‑releasing peptide (KP‑102, similar to GHRP‑2) was shown to activate specific brain cells in the arcuate nucleus that are known to make growth‑hormone‑releasing factor (GRF). This suggests the peptide works partly by stimulating the brain, not just the pituitary gland.

Growth hormone-releasing hexapeptide (GHRP) stimulates GH secretion by acting on both the pituitary and the hypothalamus through a poorly understood mechanism. To reveal the hypothalamic action of GHRP, rat brains were processed for in situ hybridization for c-fos mRNA as a marker of neuronal activity after systemic administration of a newly developed GHRP, KP-102. Hypophysectomized adult male Wistar rats were administered KP-102 through an indwelling right atrial cannula. KP-102 treatment was accompanied by transient expression of the c-fos gene selectively in the ventromedial and ventrolateral regions of the arcuate nucleus (ARC). The distribution of c-fos gene-expressing cells overlapped that of GRF mRNA-containing neurons in the ventrolateral region on adjacent sections, whereas few c-fos mRNA signals were detected in the dorsomedial region where somatostatin mRNA signals were localized. To confirm this observations, hypothalamic sections were subjected to double-label in situ hybridization. Twenty-three percent of c-fos mRNA-containing cells were GRF neurons, comprising 20% of the GRF neurons in the ARC. The remaining c-fos mRNA containing cells were unidentified. KP-102 thus appears to act on a subpopulation of GRF neurons and unidentified cells in the ARC to stimulate GH secretion.