THE EFFECTS OF PYROGLUTAMYLGLUTAMYLPROLINEAMIDE, A PEPTIDE RELATED TOTHYROTROPIN-RELEASING-HORMONE, ON VAT ANTERIOR-PITUITARY-CELLS IN CULTURE

Pyroglutamylglutamylprolineamide, which was first discovered in mammal ian prostate, differs from thyrotrophin-releasing hormone (TRH) by sub stitution of glutamic acid for histidine at position two of the tripep tide. Recently, the newly discovered peptide has been identified in su bstantial concentrations in the rat anterior pituitary gland and, in t his study, we have investigated the effects of the peptide on rat ante rior pituitary cells in culture. GH(3) cells were chosen to examine th e possible effects of the new peptide, particularly in relation to its effects on the TRH receptor. This cell-type was deficient, in compari son with normal rat pituitary cells, in the new TRH-related peptide an d 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 secret ion 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-li ke activity causing stimulation of both GH and prolactin release from GH(3) cells. Both TRH and pGlu-Glu-ProNH(2) appeared to act through th e same intracellular signalling mechanism, causing significant increas es in intracellular inositol phosphate within the expected concentrati on 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, sug gesting that the effects of the new peptide were mediated through a se cond receptor. The physiological relevance of these effects of pGlu-Gl u-ProNH(2) requires further investigation.