Experimental data indicate that antagonists of
growth hormone-releasing hormone (GHRH) could be used clinically in disorders characterized by excessive GHRH/
growth hormone (GH) secretion, but direct evidence for the effectiveness of GHRH antagonists on human pituitary tissue is still lacking. In this study, we investigated the inhibitory effect of our GHRH antagonists
MZ-4-71 and
JV-1-36 and the
somatostatin (SST) analog
RC-160 on superfused pituitary cells obtained from a human GH-secreting
adenoma. Using Western blot analysis and immunohistochemistry, we demonstrated profuse expression of the
GHRH receptor and its major splice variant SV1 and an increase in the expression of Gsa
protein in the
adenoma tissue. Exposure of the
tumor cells to exogenous pulses of GHRH induced definite GH responses, causing a 3- to 5-fold elevation of the basal GH level. The antagonists
MZ-4-71 and
JV-1-36 did not alter basal GH secretion, indicating that the
adenoma cells did not secrete GHRH in an autocrine manner. However, both antagonists prevented the stimulatory effect of exogenous GHRH. Similarly to the GHRH antagonists, neither SST-14 nor the SST analog
RC-160 had an effect on the basal GH secretion of the
tumor cells, but both
peptides inhibited the stimulatory effect of exogenous GHRH, with
RC-160 being more potent than SST. Our study provides direct evidence for the effectiveness of potent GHRH antagonists such as
MZ-4-71 and
JV-1-36 on human pituitary GH-secreting
adenoma tissue and strongly suggests that these drugs could be used for
therapy of GHRH-associated forms of
acromegaly, particularly for those patients in whom surgery fails or is not an option.