Cryptic peptides of prepro-TRH antagonize TRH-induced GH secretion in chickens at extrapituitary sites.
Complete processing of the TRH precursor in the rat hypothalamus generates TRH and a number of other "cryptic' peptides that flank the TRH progenitor sequences. Two of these peptides, P4 (Ser-Phe-Pro-Trp-Met-Glu-Ser-Asp-Val-Thr; present between amino acids 160 and 169 of rat prepro-TRH) and P5 (Phe-Ile-Asp-Pro-Gly-Leu-Gln-Arg-Ser-Trp- Glu-Glu-Lys-Glu-Gly-Glu-Gly-Val-Leu-Met-Pro-Glu; present between amino acids 178 and 199 of rat prepro-TRH), have recently been shown to modulate TRH-induced GH and thyrotrophin release from rat pituitary glands. The possibility that these peptides might modulate GH secretion in chickens was examined, since TRH is a physiological GH-releasing factor in birds. The administration of P4 and P5 (at doses of 10 and 100 micrograms/kg) consistently lowered basal plasma GH concentrations 30 and 60 min after a bolus i.v. injection. Pretreatment with P4 and P5 similarly suppressed the GH response to systemic TRH challenge. The GH-releasing activity of maximally stimulatory doses of TRH was also reduced by concomitant injections of either P4 (100 micrograms/kg) or P5 (100 micrograms/kg), which blocked the GH-releasing activity of submaximally effective doses of TRH. In marked contrast, neither P4 nor P5 significantly affected basal or TRH-induced GH release from chicken pituitary glands incubated in vitro. These results demonstrate novel actions of P4 and P5 on hypothalamic-pituitary function and, for the first time, indicate extrapituitary sites of action for these cryptic peptides in modulating anterior pituitary function.
Harvey
S
S
Department of Food and Animal Sciences, University of Delaware, Newark 19717-1303, USA.
Cogburn
L A
LA
D000818:Animals; D002645:Chickens / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects; D011498:Protein Precursors / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D013997:Time Factors
D010446:Peptide Fragments; D011498:Protein Precursors; C063596:prepro-thyrotropin-releasing hormone; C057640:prepro-thyrotropin-releasing hormone (178-199); D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone