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Pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH₂) is a tripeptide with structural and immunological similarities to thyrotrophin-releasing hormone (TRH; pGlu-His-ProNH₂). Since TRH stimulates GH secretion in domestic fowl, the possibility that pGlu-Glu-ProNH₂ may also provoke GH release was investigated. Unlike TRH, pGlu-Glu-ProNH₂ alone had no effect on GH release from incubated chicken pituitary glands and did not down-regulate pituitary TRH receptors. However, pGlu-Glu-ProNH₂ suppressed TRH-induced GH release from pituitary glands incubated in vitro and competitively displaced [³H]methyl³-histidine²-TRH from pituitary membranes. Systemic injections of pGlu-Glu-ProNH₂ had no significant effect on basal GH concentrations in conscious birds, but promptly lowered circulating GH levels in sodiumpentobarbitone anaesthetized fowl. Submaximal GH responses of conscious and anaesthetized birds to systemic TRH challenge were, however, potentiated by prior or concomitant administration of pGlu-Glu-ProNH₂. These results demonstrate, for the first time, that pGlu-Glu-ProNH₂ has biological activity, with inhibitory and stimulatory actions within the avian hypothalamo-pituitary axis. These results indicate that pGlu-Glu-ProNH₂ may act as a TRH receptor antagonist within this axis.

Journal of Endocrinology (1993) 138, 137–147

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