GROWTH-HORMONE (GH)-RELEASING PEPTIDE STIMULATION OF GH RELEASE FROM HUMAN SOMATOTROPH ADENOMA CELLS - INTERACTION WITH GH-RELEASING HORMONE, THYROTROPIN-RELEASING-HORMONE, AND OCTREOTIDE
U. Renner et al., 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 Journal of clinical endocrinology and metabolism, 78(5), 1994, pp. 1090-1096
The synthetic hexapeptide GH-releasing peptide (GHRP; His-D-Trp-Ala-Tr
p-D-Phe-Lys-NH2) specifically stimulates GH secretion in humans in viv
o 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 OH-relea
sing hormone (GHRH), TRH, and the somatostatin analog octreotide. GH s
ecretion of all 12 adenoma cultures could be stimulated with GHRP, whe
reas GHRH was active only in 6 adenoma cultures. In GHRH-responsive ce
ll cultures, simultaneous application of GHRH and GHRP had an additive
effect on GH secretion. TRH stimulated GH release in 4 of 7 adenoma c
ultures; in TRH-responsive cell cultures there was also an additive ef
fect of GHRP and TRH on GH secretion. In 5 of 9 adenoma cultures inves
tigated, octreotide inhibited basal GH secretion. In these cell cultur
es, GHRP-induced GH release was suppressed by octreotide. In 5 of 5 ca
ses, the protein kinase-C inhibitor phloretin partly inhibited GHRP-st
imulated GH release, but not basal GH secretion. In summary, GH secret
ion was stimulated by GHRP in all somatotroph adenomas investigated, i
ndicating that its unknown receptor and signaling pathway are expresse
d more consistently in somatotroph adenoma cells than these for GHRH,
TRH, and somatostatin. Our data give further evidence that GHRP-stimul
ated GH secretion is mediated by a receptor different from that for GH
RH or TRH, respectively, and that protein kinase-C is involved in the
signal transduction pathway. Because human somatotroph adenoma cell cu
ltures respond differently to various neuropeptides (GHRH, TRH, somato
statin, and others), they provide a model for further investigation of
the mechanism of action of GHRP-induced GH secretion.