High levels of thyrotropin-releasing hormone precursor peptide immunoreactivity and binding substance occur in human cerebrospinal fluid.
A thyrotropin-releasing hormone (TRH) precursor peptide, pGlu-His-Pro-Gly (TRH-Gly) and related peptides were measured in human cerebrospinal fluid (CSF) with a TRH-Gly radiommunoassay and the levels of immunoreactivity (IR) were found to be 136- to 352-fold higher than the corresponding levels of TRH-IR. TRH-IR levels in CSF are elevated during the active phase of multiple sclerosis (MS). We have used this TRH-Gly RIA to determine whether this TRH precursor peptide is also elevated in CSF from MS and Alzheimer's (ALZ) disease patients in comparison with the corresponding levels in non-central nervous system disease (control) patients. A highly significant increase in TRH-Gly-IR was observed in MS and ALZ CSF samples compared to control CSF. Cation exchange and exclusion chromatography of extracts of mixtures of CSF and synthetic TRH-Gly revealed two peaks of TRH-Gly-IR. One cochromatographed with synthetic TRH-Gly and the other was attributable to the formation of a complex between TRH-Gly and a binding substance originating in CSF. Corresponding studies with extracts of mixtures of CSF and synthetic TRH revealed no evidence for TRH binding with any component of CSF. Reverse-phase high-pressure liquid chromatography of pooled extracts of normal CSF revealed that about a third of the total TRH-Gly-IR coeluted with synthetic TRH-Gly. The half-time for in vitro metabolism of synthetic TRH-Gly in fresh CSF was 5 times longer than for synthetic TRH at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Pekary
A E
AE
Endocrinology Research Laboratory, Veterans Administration Wadsworth Medical Center, Los Angeles, Calif.
Gwirtsman
H
H
Tourtellotte
W W
WW
Smith
V P
VP
Hershman
J M
JM
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D011498:Protein Precursors / Q000134:cerebrospinal fluid* / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid* / Q000737:chemistry
D011498:Protein Precursors; D013973:Thyrotropin-Releasing Hormone; C040476:thyrotropin-releasing hormone, Gly; C046418:pro-thyrotropin releasing hormone; D011761:Pyrrolidonecarboxylic Acid