Growth Hormone (GH)-Releasing Peptide Stimulation of GH Release from Human Somatotroph Adenoma Cells: Interaction with GH-Releasing Hormone, Thyrotropin- Releasing Hormone, and Octreotide.

The synthetic hexapeptide GH-releasing peptide (GHRP;
His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) specifically stimulates GH
secretion in humans in vivo and in animals in vitro and in vivo via
a still unknown receptor and mechanism. To determine the effect of
GHRP on human somatotroph cells in vitro, we stimulated cell
cultures derived from 12 different human somatotroph adenomas with
GHRP alone and in combination with GH-releasing hormone (GHRH),
TRH, and the somatostatin analog octreotide. GH secretion of all 12
adenoma cultures could be stimulated with GHRP, whereas GHRH was
active only in 6 adenoma cultures. In GHRH-responsive cell
cultures, simultaneous application of GHRH and GHRP had an additive
effect on GH secretion. TRH stimulated GH release in 4 of 7 adenoma
cultures; in TRH-responsive cell cultures there was also an
additive effect of GHRP and TRH on GH secretion. In 5 of 9 adenoma
cultures investigated, octreotide inhibited basal GH secretion. In
these cell cultures, GHRP-induced GH release was suppressed by
octreotide. In 5 of 5 cases, the protein kinase-C inhibitor
phloretin partly inhibited GHRP-stimulated GH release, but not
basal GH secretion. In summary, GH secretion was stimulated by GHRP
in all somatotroph adenomas investigated, indicating that its
unknown receptor and signaling pathway are expressed more
consistently in somatotroph adenoma cells than those for GHRH, TRH,
and somatostatin. Our data give further evidence that
GHRP-stimulated GH secretion is mediated by a receptor different
from that for GHRH or TRH, respectively, and that protein kinase-C
is involved in the signal transduction pathway. Because human
somatotroph adenoma cell cultures respond differently to various
neuropeptides (GHRH, TRH, somatostatin, and others), they provide a
model for further investigation of the mechanism of action of
GHRP-induced GH secretion.