Absence of detectable circadian rhythmicity of neurophysin I, a surrogate marker for oxytocin.

PURPOSE: Oxytocin (OXT) plays key roles in social behaviour, stress regulation, and reproductive physiology. OXT deficiency has been described in pituitary disorders and is associated with increased anxiety and impaired prosocial behaviour. Despite growing clinical interest, the circadian regulation of OXT remains poorly defined, largely due to methodological limitations in measuring endogenous OXT. Neurophysin I (NP-I), a stable carrier protein co-released with OXT, represents a reliable surrogate marker. Characterizing the circadian profile of NP-I may therefore provide important insights into oxytocinergic function with implications for diagnostics and future replacement strategies. METHODS: This study is a secondary analysis of a prospective, observational trial conducted in healthy adults under highly standardized conditions. Thirteen participants underwent hourly blood sampling over 24 h following overnight fasting, controlled fluid intake, standardized meals, and regulated light exposure and physical activity. All assessments were performed on the clinical research ward to minimize external influences on hormone secretion. RESULTS: Thirteen healthy participants (median age 23 years [IQR, 19–24]; 46% female; BMI 22.8 ± 1.6 kg/m²) underwent 24-hour hormone profiling. NP-I concentrations ranged from 50 to 8,607 pg/mL. The overall median NP-I concentration was 822 pg/mL [339–1,392], with a mean of 1,609 pg/mL (2,084). Individual median 24-hour NP-I concentrations ranged from 143 pg/mL [114–186] to 7,103 pg/mL [6,380–7,714]. Across participants, NP-I levels peaked at approximately 05:30 and reached a nadir at approximately 16:30. The estimated oscillation amplitude was small (35 pg/mL) and not statistically significant (95% CI −110 to 181; p > 0.05), indicating the absence of a robust population-level circadian rhythm. Female participants exhibited higher NP-I concentrations than males (median 1,372 pg/mL [468–5,344] vs. 687 pg/mL [297–932]), with markedly elevated levels—approximately four- to five-fold higher—in two women using hormonal contraception. CONCLUSION: Under resting, unstimulated conditions, circulating NP-I levels in healthy adults do not display significant circadian rhythmicity, suggesting stable basal oxytocinergic output. Exploratory findings indicate potential sex-related differences that warrant further investigation.