Recent studies have revealed that TRH-like immunoreactivity (TRH-LI) in human serum is predominantly pGlu-Glu-ProNH2 (<EEP-NH2), a peptide previously found in, among others tissues, the pituitary gland of various mammalian species. In the rat pituitary, <EEP-NH2 is present in gonadotrophs and its pituitary content is regulated by gonadal steroids and gonadotrophin- releasing hormone (GnRH). Hence, we reasoned that <EEp-NH2 in human serum may also arise, at least in part, from the pituitary, and that its secretion may correlate with that of gonadotrophins. Therefore, blood was simultaneously sampled from both inferior petrosal sinuses, which are major sites of the venous drainage of the pituitary gland, and a peripheral vein from seven patients with suspected adrenocorticotrophin-secreting pituitary tumours. In addition, in six postmenopausal and six cyclic women, peripheral vein blood was collected at 10-min intervals for 6 h, then a standard 100 μg GnRH test was performed. In the sera, TRH-LI was estimated by RIA with antiserum 4319, which binds most tripeptides that share the N- and C-terminal amino acids with TRH (pGlu-His-ProNH2). In addition, LH and FSH were measured in these sera by RIA. In the blood samples taken at 10-min intervals, an episodic variation in serum TRH-LI was noted and pulses of TRH- LI were detected at irregular intervals (from one to six pulses per 6 h) in five postmenopausal and six cyclic women. In general, these pulses did not coincide with those of LH and FSH, suggesting that TRH-LI is not co-secreted with gonadotrophins. Moreover, unlike LH and FSH, serum TRH-LI did not increase during the menopause or after exogenous administration of GnRH. Whereas gonadotrophin concentrations were significantly greater an the inferior petrosal sinus than in peripheral serum, there were no differences in TRH-LI concentrations between these serum samples. In conclusion, serum TRH-LI in humans seems not to be regulated by gonadal steroids or GnRH. Moreover, serum derived directly from the pituitary contained no more TRH-LI than did peripheral serum, which suggests that the human pituitary gland does nor secrete significant amounts of <EEP-NH2, and therefore does not contribute significantly to serum TRH-LI concentrations. Further research is required to identify the site of origin of <EEP-NH2 in human serum.

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Journal Journal of Endocrinology
de Greef, W.J, de Herder, W.W, Lambalk, C.B, Klootwijk, W, Sleddens-Linkels, E, de Jong, F.H, & Visser, T.J. (1997). Evidence that the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in human serum may not be secreted by the pituitary gland. Journal of Endocrinology, 155(2), 393–399. doi:10.1677/joe.0.1550393