Synchronicity of Frequently Sampled Thyrotropin (TSH) and Leptin Concentrations in Healthy Adults and Leptin-Deficient Subjects: Evidence for Possible Partial TSH Regulation by Leptin in Humans
Abstract
Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24 h in five healthy men and found that both leptin and TSH levels are highly organized and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH and leptin levels reaching a nadir in late morning and a peak in the early morning hours. Importantly, cosinor analysis on the absolute leptin and TSH levels revealed a statistically significant fit for a 24-h period and the two hormones showed similar probabilities of rhythm and superimposable peak values. Furthermore, this study shows a strong positive Pearson correlation between the 24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the ultradian fluctuations in leptin levels showed pattern synchrony with those of TSH as determined by cross-correlation analysis, by cross-approximate enthropy and Bayessian analysis applied independently. To further explore whether these associations could reflect an underlying regulation of TSH secretion by leptin, we also studied frequently sampled leptin and TSH levels in four brothers, members of a family with leptin deficiency (one normal homozygote, two heterozygotes, and one leptin-deficient homozygote). Leptin levels of the homozygous leptin-deficient subject are detectable but bioinactive, and the rhythm of his TSH is disorganized. 24-h pattern of leptin and TSH variability in the heterozygous subjects, although significantly correlated, showed a weaker correlation compared with the strong correlation in the normal subjects. These data are consistent with the possibility that leptin may regulate TSH pulsatility and circadian rhythmicity, but interventional studies are needed to definitively prove whether leptin regulates the minute-to-minute oscillations and ultradian rhythm of TSH levels.
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In healthy men, leptin and TSH rhythms exhibit a similar 24-hour pattern of variability with significant pattern synchrony of ultradian fluctuations, a pattern that is impaired in leptin-deficient subjects.
“In healthy men, we have found that leptin and TSH rhythms exhibit a similar 24-hour pattern of variability with significant pattern synchrony of ultradian fluctuations, a pattern that is impaired in leptindeficient subjects (23).”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [23]
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- Authors
- Mantzoros, C. S., Ozata, M., Negrao, A. B., Suchard, M. A., Ziotopoulou, M., Caglayan, S., Elashoff, R. M., Cogswell, R. J., Negro, P., Liberty, V., Wong, M.-L., Veldhuis, J., Ozdemir, I. C., Gold, P. W., Flier, J. S., & Licinio, J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of California, Los Angeles (US)
- National Institutes of Health (US)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2001-07
- Volume
- 86
- Issue
- 7
- Pages
- 3284-3291
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2119367457
- Cited by
- 229
- References
- 0
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 10 · 2022: 2 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 10 · 2017: 7 · 2016: 14 · 2015: 10 · 2014: 12 · 2013: 11 · 2012: 7
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (46200, RR 01032)
- National Institute of General Medical Sciences (GM-08042, T32GM008042)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200, P30 DK-46200)
- National Center for Research Resources (M01-RR-01032, M01RR001032)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- leptin, thyroid-stimulating hormone, ultradian rhythms, circadian rhythm, hypothalamic-pituitary-thyroid axis, leptin deficiency
- MeSH terms
- Adult, Circadian Rhythm, Heterozygote, Homozygote, Humans, Male, Periodicity, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Triiodothyronine, Leptin
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