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Effect of Growth Hormone‐Releasing Peptide‐2 (GHRP‐2) and GH‐Releasing Hormone (GHRH) on the cAMP Levels and GH Release from Cultured Acromegalic Tumours
Author(s) -
Chen Chen,
Pullar Michael,
Loneragan Kylie,
Zhang Jin,
Clarke Iain J
Publication year - 1998
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1998.00233.x
Subject(s) - medicine , endocrinology , growth hormone–releasing hormone , acromegaly , growth hormone , hormone , peptide hormone , gonadotropin releasing hormone , peptide , chemistry , luteinizing hormone , biochemistry
There is a difference between the sheep and rat somatotrophs in the response to growth hormone‐releasing peptide‐2 (GHRP‐2), which raises the question of what the response may be in human somatotrophs. In the present study, cells were obtained from seven human acromegalic tumours and the effects of GHRP‐2 were studied. Cells were dissociated and kept in primary culture for 1–3 weeks before experimentation. Application of GHRP‐2 for 30 min induced a significant increase in GH secretion from the cultured cells from all seven tumours whereas human GH‐releasing hormone (hGHRH) at a dose of 10 nM induced a significant GH release in only four of seven tumours. The intracellular levels of cAMP in all seven tumours were significantly increased by both 10 nM GHRP‐2 and GHRH, but the response to GHRH was significantly higher than the response to GHRP‐2. The adenylyl cyclase inhibitor, MDL 12330A, blocked the effect of GHRH and GHRP‐2 on intracellular cAMP levels, whereas the Ca 2+ channel blocker Co 2+ (0.5 mM) did not attenuate the cAMP response. For the tumours in which GH secretion was increased by GHRH and GHRP‐2, the cAMP antagonist Rp‐cAMP blocked the GH response to GHRH but not to GHRP‐2. When a protein kinase A (PKA) inhibitor (H 89 ) was applied, GHRH stimulated GH release was blocked, but cAMP accumulation was not affected. The response to GHRP‐2 was not altered by H 89 . Calphostin C [a protein kinase C (PKC) inhibitor] reduced the effect of GHRP‐2 on the secretion of GH but did not affect the response to GHRH. Both GHRH and GHRP‐2 increased the intracellular Ca 2+ concentration in a concentration‐dependent manner. We conclude that (1) GHRH increases GH secretion from human GH tumours via the cAMP pathway whereas GHRP‐2 increases GH secretion mainly via the PKC pathway; (2) GHRH increases cAMP (without GH release) in a subset of tumours whereas GHRP‐2 increases cAMP levels (slightly) and GH secretion in all tumours; and (3) GHRP‐2 and GHRH do not act on the same receptor on human somatotrophs derived from acromegalic tumours.