A cryptic peptide (160-169) of thyrotropin-releasing hormone prohormone demonstrates biological activity in vivo and in vitro.

Abstract

TRH is synthesized as a precursor peptide containing five copies of the sequence Gln-His-Pro-Gly, QHPG, flanked by paired basic amino acids, and linked by other peptides. We tested one cryptic peptide, PPT (160-169, SFPWMESDVT), as a possible physiological regulator of pituitary activity in vivo. Male rats were cannulated (jugular) and received a single dose of either PPT or TRH (10(-8)-10(-6) M). PPT caused no consistent effects on either TSH or PRL secretion, while TRH stimulated the secretion of both hormones. However, PPT stimulated a dose-dependent increase in both pituitary TSH beta and PRL mRNA content at 240 min similar to TRH. In primary cultures of rat pituitaries, PPT stimulated a maximum 4-fold increase in TSH beta mRNA and a 2-fold increase in PRL mRNA in 4 h, while TRH increased both TSH beta and PRL mRNA approximately 3-fold. Again, PPT had no significant effect on TSH or PRL secretion into the medium. Thus, PPT appears to be a physiological regulator of both TSH and PRL synthesis, but, unlike TRH, does not act as a secretagogue.

Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene

“…In the TRH Ϫ͞Ϫ mice, five copies of the TRH progenitor sequence and its intervening peptides were simultaneously disrupted. Although several studies have shown biological activities of the intervening peptides on pituitary hormones, the results are still contradictory (36)(37)(38)(39)(40), and pathological roles of the intervening peptides in development of hyperglycemia of the TRH Ϫ͞Ϫ mice remain to be determined.…”

Distribution, Cellular Localization, and Ontogeny of Preprothyrotropin-Releasing Hormone-(160–169) (Ps4)-Binding Sites in the Rat Pituitary1

“…2) Authentic Ps4 is released from hypothalamic neurons in vitro (4,5), and substantial amounts of Ps4 are found in the hypophysial portal blood (26). 3) Synthetic Ps4 has been shown to potentiate TRH-induced TSH release (6,8) and to increase TSH and PRL gene expression (27,28 (3-10), whereas the [Tyr 0 ]Ps4 analog is resistant to enzymatic degradation (6). Moreover, addition of a Tyr residue at the N-terminus of Ps4 has been shown to increase the binding affinity of the peptide (10,11).…”

Specific binding sites for rat prepro‐TRH‐(160–169) on C6 glioma and BN1010 clonal neural cells

“…Interestingly, it was demonstrated that Ps4, like TRH, induces a dose-dependent increase of ß-TSH mRNA content in intact animals, primary pituitary cell cultures and in a heterologous TSH expression assay [7,8]. Recently, another group has revealed the biological importance of Ps4 in the dorsal motor nucleus of the vagus, a region where TRH plays a pivotal role to activate directly neurons leading to the stimulation of vagai outflow to the stomach and gastric function.…”