Urinary oxytocin as a non-invasive biomarker for neurohypophyseal hormone secretion.
The objective was to characterize the urinary oxytocin (OT) system with the goal of using it as a biomarker for neurohypophyseal peptide secretion. We studied urinary OT secretion in mice under three conditions: (1) in OT gene deletion mice (OT -/-) which lack the ability to produce the peptide; (2) after arterial vascular infusion of OT and (3) after physiological stimulation with consumption of 2% sodium chloride. OT was measured by radioimmunoassay (RIA) and Surface-Enhanced Laser Desorption Ionization Time of Flight Mass Spectroscopy (SELDI TOF MS). In OT -/- mice (n=25), urinary OT levels were not detectable, while in OT +/+ mice (n=23) levels were 250.2+/-35.3 pg/ml. To evaluate blood/urine transfer, mice with chronic carotid arterial catheters were infused with saline or OT (5 or 20 pmol/min). Peak urine OT levels were 89+/-11.5 and 844+/-181 ng/ml in the low and high OT groups, respectively. Proteomic evaluation showed MS peaks, corresponding to OT ( approximately 1009 Da) and a related peptide ( approximately 1030 Da) with highest levels in mice infused with OT. Salt loading (5 days of 2% NaCl as drinking water) increased plasma osmolality (3.3%), increased plasma and urinary vasopressin (AVP), but caused no changes in OT. Thus, using non-invasive urine samples, we document that urinary OT and AVP can be used to monitor changes in peptide secretion. Urinary OT and AVP, as well as other urinary peptides, may provide a viable biomarker for peptide secretion and may be useful in clinical studies.
Polito
Anthony B
AB
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.
Goldstein
David L
DL
Sanchez
Lylian
L
Cool
David R
DR
Morris
Mariana
M
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002339:Carotid Arteries; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009994:Osmolar Concentration; D010121:Oxytocin / Q000008:administration & dosage / Q000378:metabolism* / Q000502:physiology*; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014667:Vasopressins / Q000097:blood / Q000652:urine
D015415:Biomarkers; D014667:Vasopressins; D012965:Sodium Chloride; D010121:Oxytocin; D003404:Creatinine