ONTOGENY OF THYROTROPIN-RELEASING-HORMONE AND PRECURSOR PEPTIDE IN THE RAT

Thyrotropin releasing hormone (TRH) and its precursor peptide pGlu-His-Pro-Gly (TRH-Gly) were measured in serum and in a variety of tissues of developing rats using specific RIA. TRH and TRH-Gly immunoreactivities were detected in most tissues. TRH concentrations were highest in pancreas, in which mean (+/- SEM) TRH concentrations were 138 +/- 20 pmol/g wet tissue 2 d before birth and 644 +/- 80 and 586 +/- 86 pmol/g, respectively, 2 and 5 d after birth. Hypothalamic TRH levels gradually increased from 4 d before birth (12 +/- 2.5 pmol/g) to 77 d of postnatal age (348 +/- 33 pmol/g). Hypothalamic concentrations were lower than levels in pancreas until 13 d of age. The mean serum TRH level at 2 d was 80 +/- 20 pmol/L and fell to the adult range by 21 d. TRH-Gly concentrations were highest in small gut (371 +/- 64 pmol/g) during the neonatal period, falling gradually to adult levels (33 +/- 4.8 pmol/g) by 35 d. Mean hypothalamic TRH-Gly concentrations increased to a peak of 62 +/- 4.5 pmol/g at 13 d, falling thereafter. High TRH-Gly concentrations (> 100 pmol/g) also were observed in pancreas (at d 2), kidney, and pituitary gland (at d 21). Serum TRH-Gly concentrations were highest (mean 417 +/- 26 pmol/L) on the 2nd postnatal day and gradually decreased to the adult level by 35 d. Changes in the TRH-Gly/TRH ratio were inversely correlated with tissue TRH concentrations in hypothalamus, pancreas, and liver. Our results suggest that 1) tissue levels of TRH-Gly and TRH are developmentally regulated, 2) the conversion of TRH-Gly to TRH varies among tissues, and 3) the major tissue site of TRH biosynthesis changes during development from liver during fetal life to pancreas in the neonatal period and to hypothalamus in the adult. The consistently high TRH-Gly/TRH ratio in serum suggests that the circulating peptides are derived from multiple and predominantly nonhypothalamic tissue sources.