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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
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, w...
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Published in: | The journal of clinical endocrinology and metabolism 2001-07, Vol.86 (7), p.3284-3291 |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | 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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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.86.7.7644 |