Growth hormone-releasing hexapeptide (GHRP-6) increases intracellular calcium concentrations in cultured cells from human pituitary adenomas of different types.
OBJECTIVE
The GH-releasing peptide GHRP-6, has been found to interact with specific receptors in somatotrophs, causing cytosolic Ca2+ ([Ca2+]i) rise and GH release. Moreover, this peptide has been demonstrated to stimulate the secretion of pituitary hormones other than GH, i.e. ACTH and prolactin, this effect being generally attributed to a central action. In this study we evaluated whether the pituitary action of this peptide is restricted to cell type of somatotroph lineage.


METHODS
The effect opf GHRP-6 on [Ca2+]i was tested in cell preparations obtained from a series of human pituitary adenomas (9 GH-secreting adenomas, 7 nonfunctioning adenomas, 3 ACTH-secreting adenomas, 2 TSH-secreting adenomas and 1 prolactinoma) loaded with the Ca2+ indicator fura-2.


RESULTS
GHRP-6, at concentrations higher than 1 nmol/l, significantly increased [Ca2+]i in all tumours, with the exception of the 3 ACTH-secreting adenomas in which the peptide was ineffective at any concentration tested (from 1 nmol/l to 1 micromol/l). By contrast, in all ACTH-secreting adenomas, both corticotrophin-releasing hormone and pituitary adenylate cyclase activating peptide caused a marked [Ca2+]i increase. In tumours responsive to GHRP-6, the peptide caused a typical biphasic [Ca2+]i rise due to Ca2+ mobilization from the intracellular stores and Ca2+ influx through voltage-dependent Ca2+ channels.


CONCLUSIONS
These data indicate that almost all tumoral pituitary cell types are targets of GHRP-6 action, the only exception being corticotrophs.
Institute of Endocrine Sciences, Maggiore Hospital IRCCS, University of Milan, Italy.
A
A
Lania
E
E
Ballaré
S
S
Corbetta
M
M
Filopanti
L
L
Persani
A
A
Spada
D000236:Adenoma / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D019070:Cell Lineage; D003600:Cytosol / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D010907:Pituitary Hormones; C041048:growth hormone releasing hexapeptide; D013007:Growth Hormone-Releasing Hormone; D002118:Calcium