pGlutamylglutamylprolineamide modulation of growth hormone secretion in domestic fowl: antagonism of thyrotrophin-releasing hormone action?
Pyroglutamyglutamylprolineamide (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 sodium-pentobarbitone 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.
Department of Physiology, University of Alberta, Edmonton, Canada.
S
S
Harvey
V L
VL
Trudeau
R J
RJ
Ashworth
S M
SM
Cockle
D000818:Animals; D002645:Chickens / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D013006:Growth Hormone / Q000097:blood* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology
D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; C059697:pyroglutamyl-glutamyl-proline amide; D013006:Growth Hormone; D011761:Pyrrolidonecarboxylic Acid