Cryptic peptides of prepro-TRH antagonize TRH-induced GH secretion in chickens at extrapituitary sites

Abstract

Abstract 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 μg/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 μg/kg) or P5 (100 μg/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. Journal of Endocrinology (1996) 151, 359–364