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
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
复制标题
DOI：
10.1210/jc.86.7.3284
复制
发表时间：
2001-07-01
影响因子：
5.8
通讯作者：
Licinio, J
中科院分区：
文献类型：
--
作者：
Mantzoros, CS;Ozata, M;Licinio, J
瘦素向大脑发出能量储备状态的信号。瘦素在体外刺激TRH的生物合成，并影响啮齿动物体内下丘脑-垂体-甲状腺轴的活性。由于血液中瘦素和TSH的水平都呈现出昼夜变化，夜间明显升高，我们试图确定循环瘦素和TSH的波动之间是否存在关系。我们在5名健康男性的24小时内每7分钟测量一次血清瘦素和TSH水平，发现瘦素和TSH水平都是高度有组织和有脉动的。瘦素和TSH节律也有类似的规律，TSH和瘦素水平在上午晚些时候达到最低点，在凌晨达到峰值。重要的是，对绝对瘦素和TSH水平的余弦分析显示，在24小时内，这两种激素显示出相似的节律概率和重叠的峰值。此外，本研究显示，健康受试者瘦素和TSH的24小时变异性模式之间存在强烈的Pearson正相关。最后，瘦素水平的超昼夜波动与TSH水平的模式同步，这是通过交叉近似熵和贝叶斯分析独立应用的相互关联分析确定的。为了进一步探索这些关联是否反映了瘦素对TSH分泌的潜在调节，我们还研究了四个兄弟的频繁取样的瘦素和TSH水平，他们是一个瘦素缺乏家族的成员，有正常纯合子、两个杂合子和一个瘦素缺乏纯合子。纯合子瘦素缺乏症患者的瘦素水平可检测到，但无生物活性，其TSH节律紊乱，杂合子患者的24小时瘦素与TSH变异性模式虽然有显著相关性，但与正常人的强相关性相比，相关性较弱。这些数据与瘦素可能调节TSH脉动和昼夜节律的可能性一致，但需要干入性研究来明确证明瘦素是否调节TSH水平的分分钟振荡和超昼夜节律。
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 24h 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. Further-more, 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 tone 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.