CRYPTIC PEPTIDES OF PREPRO-TRH ANTAGONIZE TRH-INDUCED GH SECRETION INCHICKENS AT EXTRAPITUITARY SITES

Complete processing of the TRH precursor in the rat hypothalamus gener ates TRH and a number of other 'cryptic' peptides that flank the TRH p rogenitor sequences. Two of these peptides, P-4(Ser-Phe-Pro-Trp-Met-Gl u-Ser-Asp-Val-Thr; present between amino acids 160 and 169 of rat prep ro-TRH) and P-5 (Phe-Ile-Asp-Pro-Gly-Leu- p-Glu-Glu-Lys-Glu-Gly-Glu-Gl y-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 t hyrotrophin release from rat pituitary glands. The possibility that th ese peptides might modulate GH secretion in chickens was examined, sin ce TRH is a physiological GH-releasing factor in birds. The administra tion of P-4 and P-5 (at doses of 10 and 100 mu g/kg) consistently lowe red basal plasma GH concentrations 30 and 60 min after a bolus i.v. in jection. Pretreatment with Pq and Pg similarly suppressed the GH respo nse to systemic TRH challenge. The GH-releasing activity of maximally stimulatory doses of TRH was also reduced by concomitant injections of either P-4 (100 mu g/kg) or P-5 (100 mu g/kg), which blocked the GH-r eleasing activity of submaximally effective doses of TRH. In marked co ntrast, neither P-4 nor P-5 significantly affected basal or TRH-induce d GH release from chicken pituitary glands incubated in vitro. These r esults demonstrate novel actions of P-4 and P-5 on hypothalamic-pituit ary function and, for the first time, indicate extrapituitary sites of action for these cryptic peptides in modulating anterior pituitary fu nction.