Hormone release in culture in response to
pituitary adenylate cyclase-activating polypeptide (
PACAP) was examined in 28 human
pituitary adenomas: 10 null cell
adenomas, 4
gonadotropin-, 6 GH-, 6
ACTH-, and 2 PRL-producing
adenomas. The effects of
PACAP38 were compared with those of the classical
hypothalamic releasing hormones and other activators of intracellular signaling pathways.
PACAP38 significantly stimulated GH release from 1 somatotrope
tumor (125 +/- 3% of control; P < 0.05) and
ACTH release from 3 corticotrope
tumors (134 +/- 6%, 136 +/- 7%, and 137 +/- 9% of control; P < 0.05). The effects of
PACAP38 were less potent than either GHRH on GH release in the somatotrope
tumor or CRH on
ACTH release in the corticotrope
tumors but similar to the responses seen with the cAMP analog
8-bromo-cAMP (8-Br-cAMP). No detectable effects of
PACAP38 on
hormone release from null cell,
gonadotropin-, or PRL-producing
adenomas were observed. Of the 5 somatotrope
tumors that failed to respond to
PACAP38, all also failed to respond to either 8-Br-cAMP, TRH, or GHRH. Of the corticotrope
tumors that failed to respond, 2 of the 3 also failed to respond to CRH. In addition to eliciting
hormone release appropriate to the
tumor type,
PACAP38 also stimulated
glycoprotein hormone alpha-subunit (alpha SU) release from one somatotrope
tumor (229 +/- 35% of control, P < 0.01) and one corticotrope
tumor (149 +/- 4% of control; P < 0.01). This response was not mimicked by 8-Br-cAMP in the somatotrope
tumor, but in the corticotrope
tumor a significant alpha SU release was also seen after stimulation with the
protein kinase C activator 12-O-tetradecanoyl-phorbol-13-acetate and 8-Br-cAMP. These results suggest that the novel hypothalamic
peptide PACAP38 has a modest role in the regulation of GH,
ACTH, and alpha SU secretion from some human tumourous pituitary corticotropes and somatotropes. Further studies are needed to elucidate the intracellular signaling pathways that mediate the effects of
PACAP on
hormone secretion by these
tumor types.