A cryptic peptide from the preprothyrotropin-releasing hormone precursor stimulates thyrotropin gene expression.
The precursor peptide of TRH (prepro-TRH) contains five copes of pro-TRH linked by other peptide sequences. These peptides are coprocessed with TRH in the median eminence of the hypothalamus and released into the portal circulation, rendering this family of peptides available to act at the level of the anterior pituitary. Therefore, we tested the potential bioactivity of one cryptic peptide, prepro-TRH amino acids 160-169 [prepro-TRH-(160-169)], in a TRH-responsive pituitary cell line (GH3). In a heterologous TSH expression assay, we found that prepro-TRH-(160-169) stimulated TSH beta gene promoter activity in a time- and dose-dependent manner; moreover, the effect of prepro-TRH-(160-169) was more rapid and of greater magnitude than that of TRH on TSH beta-directed chloramphenicol acetyltransferase synthesis. In the same cells, we found that prepro-TRH-(160-169) stimulated PRL synthesis and secretion, but the effect was similar in magnitude and duration to that of TRH. The effect of prepro-TRH-(160-169) appears to be additive to that of TRH, suggesting that prepro-TRH-(160-169) may act through a mechanism separate from that of TRH. Thus, prepro-TRH-(160-169) has potent endocrinological effects at the level of the genome.
Carr
F E
FE
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, D.C. 20307.
Reid
A H
AH
Wessendorf
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000096:biosynthesis / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011498:Protein Precursors / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013972:Thyrotropin / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*
D010446:Peptide Fragments; D011498:Protein Precursors; C063596:prepro-thyrotropin-releasing hormone; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013972:Thyrotropin