EVIDENCE THAT THE TRH-LIKE PEPTIDE PYROGLUTAMYL-GLUTAMYL-PROLINEAMIDEIN HUMAN SERUM MAY NOT BE SECRETED BY THE PITUITARY-GLAND

Recent studies have revealed that TRH-like immunoreactivity (TRH-LI) i n human serum is predominantly pGlu-Glu-ProNH(2) (<EEP-NH2), a peptide previously found in, among others tissues, the pituitary gland of var ious mammalian species. In the rat pituitary, <EEP-NH2 is present in g onadotrophs 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 pitu itary, and that its secretion may correlate with that of gonadotrophin s. Therefore, blood was simultaneously sampled from both inferior petr osal sinuses, which are major sites of the venous drainage of the pitu itary gland, and a peripheral vein from seven patients with suspected adrenocorticotrophin-secreting pituitary rumours. In addition, in six postmenopausal and six cyclic women, peripheral vein blood was collect ed at 10-min intervals for 6 h, then a standard 100 mu g GnRH test was performed. In the sera, TRH-LI was estimated by RIA with antiserum 43 19, which binds most tripeptides that share the N- and C-terminal amin o acids with TRH (pGlu-His-ProNH(2)), In addition, LH and FSH were mea sured in these sera by RIA. In the blood samples taken at 10-min inter vals, an episodic variation in serum TRH-LI was noted and pulses of TR H-LI were detected at irregular intervals from one to six pulses per 6 h) in five postmenopausal and six cyclic women. In general, these pul ses did not coincide with those of LH and FSH, suggesting that TRH-LI is not co-secreted with gonadotrophins. Moreover, unlike LH and FSH, s erum TRH-LI did not increase during the menopause or after exogenous a dministration of GnRH. Whereas gonadotrophin concentrations were signi ficantly greater in the inferior petrosal sinus than in peripheral ser um, there were no differences in TRH-LI concentrations between these s erum samples. In conclusion, serum TRH-LI in humans seems not to be re gulated 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 not secrete signif icant amounts of <EEP-NH2, and therefore does not contribute significa ntly to serum TRH-LI concentrations. Further research is required to i dentify the site of origin of <EEP-NH2 in human serum.