GROWTH-HORMONE (GH)-RELEASING PEPTIDE STIMULATION OF GH RELEASE FROM HUMAN SOMATOTROPH ADENOMA CELLS - INTERACTION WITH GH-RELEASING HORMONE, THYROTROPIN-RELEASING-HORMONE, AND OCTREOTIDE

Citation
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
Citations number
30
Categorie Soggetti
Endocrynology & Metabolism
ISSN journal
0021972X
Volume
78
Issue
5
Year of publication
1994
Pages
1090 - 1096
Database
ISI
SICI code
0021-972X(1994)78:5<1090:G(PSOG>2.0.ZU;2-J
Abstract
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.