Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women
Open accessAbstract
Leptin, an adipocyte hormone, is a trophic factor for the reproductive system; however, it is still unknown whether there is a dynamic relation between fluctuations in circulating leptin and hypothalamic—pituitary–ovarian (HPO) axis hormones. To test the hypothesis that fluctuations in plasma leptin concentrations are related to the levels of luteinizing hormone (LH) and estradiol, we sampled plasma from six healthy women every 7 min for 24 h during days 8–11 of the menstrual cycle. Cross-correlation analysis throughout the 24-h cycle revealed a relation between release patterns of leptin and LH, with a lag of 42–84 min but no significant cross-correlation between LH and estradiol. The ultradian fluctuations in leptin levels showed pattern synchrony with those of both LH and estradiol as determined by cross-approximate entropy (cross-ApEn). At night, as leptin levels rose to their peak, the pulsatility profiles of LH changed significantly and became synchronous with those of leptin. LH pulses were fewer, of longer duration, higher amplitude, and larger area than during the day. Moreover, the synchronicity of LH and leptin occurred late at night, at which time estradiol and leptin also exhibited significantly stronger pattern coupling than during the day. We propose that leptin may regulate the minute-to-minute oscillations in the levels of LH and estradiol, and that the nocturnal rise in leptin may determine the change in nocturnal LH profile in the mid-to-late follicular phase that precedes ovulation. This may explain the disruption of hypothalamic—pituitary–ovarian function that is characteristic of states of low leptin release, such as anorexia nervosa and cachexia.
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In healthy women, ultradian fluctuations in leptin levels are synchronous with both LH and estradiol fluctuations.
“In healthy women, ultradian fluctuations in leptin levels are synchronous with both LH and estradiol fluctuations (24).”
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 [24]
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- Authors
- Licinio, J., Negrão, A. B., Mantzoros, C., Kaklamani, V., Wong, M.-L., Bongiorno, P. B., Mulla, A., Cearnal, L., Veldhuis, J. D., Flier, J. S., McCann, S. M., & Gold, P. W.
- Affiliations
- Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1284; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; Department of Internal Medicine and National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center,...
- National Institutes of Health (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-03-03
- Volume
- 95
- Issue
- 5
- Pages
- 2541-2546
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC19406
- OpenAlex
- W2102623180
- Cited by
- 287
- References
- 59
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 5 · 2012: 18
- FWCI
- 30.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (28934)
- U.S. Public Health Service (1R01-147991, R01 43900)
- National Institute of Mental Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Child Health and Human Development
- National Center for Research Resources (M01RR001032)
- NIH Clinical Center
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-28934, P30HD028934, U54HD028934, P50HD028934)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin, luteinizing hormone, estradiol, hypothalamic-pituitary-ovarian axis, pulsatile hormone secretion, menstrual cycle, follicular phase, cross-approximate entropy, cross correlation function, anorexia nervosa, cachexia
- MeSH terms
- Activity Cycles, Adult, Blood Specimen Collection, Circadian Rhythm, Estradiol, Female, Follicular Phase, Humans, Hypothalamo-Hypophyseal System, Luteinizing Hormone, Ovary, Proteins, Radioimmunoassay, Reference Values, Entropy, Leptin
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