THE EFFECTS OF PYROGLUTAMYLGLUTAMYLPROLINEAMIDE, A PEPTIDE RELATED TO THYROTROPIN-RELEASING-HORMONE, ON RAT ANTERIOR-PITUITARY-CELLS IN CULTURE

Pyroglutamylglutamylprolineamide, which was first discovered in mammalian prostate, differs from thyrotrophin-releasing hormone (TRH) by substitution of glutamic acid for histidine at position two of the tripeptide. Recently, the newly discovered peptide has been identified in substantial concentrations in the rat anterior pituitary gland and, in this study, we have investigated the effects of the peptide on rat anterior pituitary cells in culture. GH(3) cells were chosen to examine the possible effects of the new peptide, particularly in relation to its effects on the TRH receptor. This cell-type was deficient, in comparison with normal rat pituitary cells, in the new TRH-related peptide and appeared to be an ideal model cell in which to study the effects of pGlu-Glu-ProNH(2). TRH (0.01-100 nM) was found to stimulate the secretion of both GH and prolactin from GH(3) cells whereas pGlu-Glu-ProNH(2) had no effect within the same concentration ranges. In contrast, at micromolar concentrations pGlu-Glu-ProNH(2) exhibited intrinsic TRH-like activity causing stimulation of both GH and prolactin release from GH(3) cells. Both TRH and pGlu-Glu-ProNH(2) appeared to act through the same intracellular signalling mechanism, causing significant increases in intracellular inositol phosphate within the expected concentration ranges, However, pGlu-Glu-ProNH(2) (up to 1 mM) displaced neither [H-3]TRH nor [H-3]MeTRH from membrane-binding sites on GH(3) cells, suggesting that the effects of the new peptide were mediated through a second receptor. The physiological relevance of these effects of pGlu-Glu-ProNH(2) requires further investigation.