Human pancreatic tumor GH-releasing factor

Area of Science:

• Endocrinology
• Molecular Biology
• Neuroscience

Background:

• Three novel peptides with growth hormone (GH) releasing activity have been recently identified and synthesized.
• These peptides, including human pancreatic tumor GH releasing factor (hpGRF)-40, were isolated from human pancreatic tumors.
• Immunological and biochemical evidence suggests these peptides may be endogenous human GH releasing hormones (GHRH).

Purpose of the Study:

• To characterize the biological effects of hpGRF peptides on pituitary hormone release.
• To investigate the signaling pathways activated by hpGRF in pituitary cells.
• To evaluate the in vivo efficacy and specificity of hpGRF-40 in humans.

Main Methods:

• Peptide isolation from human pancreatic tumors and chemical synthesis.
• In vitro studies using cultured rat pituitary cells to assess effects on GH, prolactin, and LH release.
• Measurement of intracellular cyclic AMP and phosphatidylinositol turnover.
• In vivo studies in humans involving intravenous administration of hpGRF-40 and measurement of various hormone levels and blood parameters.

Main Results:

• hpGRF stimulates GH release and cyclic AMP production in rat pituitary cells, an effect inhibited by somatostatin.
• hpGRF also stimulates phosphatidylinositol turnover, which is not inhibited by somatostatin.
• Intravenous administration of hpGRF-40 in humans rapidly stimulates GH release without affecting prolactin, TSH, LH, cortisol, glucose, or other tested hormones.
• Dose-response studies showed no difference in maximal GH levels with varying hpGRF doses.

Conclusions:

• hpGRF peptides, particularly hpGRF-40, are potent stimulators of GH release.
• The signaling mechanisms involve both cyclic AMP and phosphatidylinositol pathways, with differential sensitivity to somatostatin.
• hpGRF-40 shows promise as a potential therapeutic agent for GH deficiency due to its specific GH-releasing activity in vivo.