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

Mantzoros, Christos S.; Özata, Metịn; Negrão, André Brooking; Suchard, Marc A.; Ziotopoulou, Mary; Çağlayan, Suat; Elashoff, Robert M.; Cogswell, Rebecca; Negro, Paolo; Liberty, Victoria; Wong, Ma Li; Veldhuis, Johannes D.; Ozdemír, I. Caglayan; Gold, Philip W.; Flier, Jeffrey S.; Licinio, Júlio

doi:10.1210/jcem.86.7.7644

Cited by 191 publications

(106 citation statements)

References 61 publications

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“…According to our results, alterations of TSH seem to effect the leptin levels independent from fT 3 and fT 4 levels in each group. All findings in this study point to a strong relationship between TSH and leptin levels in corroboration of some studies [2,14,18].…”

Section: Discussionsupporting

confidence: 92%

“…One of them may be TSH which, as opposed to thyrotropic releasing hormone (TRH), circulates in significant concentrations and exhibits strong pulsatility. In fact, Mantzoros et al have shown in a systematically and mathematically validated analysis that TSH and leptin exhibit coordinated pulsatility [2]. Menendez et al have shown in their recent study that TSH significantly stimulates leptin secretion by human adipose tissue in vitro, suggesting a new mechanism in the interrelationship between the adipose organ and the thyroid axis [18].…”

Section: Discussionmentioning

confidence: 99%

“…There are several studies concerning the action of leptin on the thyroid axis. In a comprehensive study, Mantzoros et al have shown that leptin and plasma TSH levels are both highly organized and pulsatile, with similar circadian rhythms [2].…”

mentioning

confidence: 99%

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TSH Influences Serum Leptin Levels Independent of Thyroid Hormones in Hypothyroid and Hyperthyroid Patients

et al. 2005

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Abstract. Leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. The physiological mechanisms for thyroid hormone-induced alteration in serum leptin are not well known. In the present study, the relationship between thyroid hormones and leptin levels was investigated in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Leptin levels were determined by radioimmunoassay and body mass index (BMI) was calculated for each subject. Serum leptin levels of 26 hypothyroid and 22 hyperthyroid patients were compared with those of 20 healthy volunteers who comprised the controls. Serum leptin levels of hypothyroid patients (28.4 ± 4.1 ng/ml) were found to be significantly higher than the controls (19.1 ± 3.2 ng/ml) (p<0.01), whereas hyperthyroid patients had lower levels (10.7 ± 1.2 ng/ml) (p<0.01). In hypothyroid patients, serum leptin levels were decreased significantly to 20.6 ± 2.1 ng/ml with thyroxin treatment (p<0.05). However, in hyperthyroid group, serum leptin levels were increased to 12.4 ± 2.2 ng/ml by treatment (p>0.05). BMI was not changed with the treatment in either group. The serum leptin levels were correlated with BMI and thyrotropin (TSH) in both hypothyroid and hyperthyroid patients. Serum leptin levels are affected in thyroid disorders and the correlation of leptin with TSH is independent of thyroid hormones.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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TSH Influences Serum Leptin Levels Independent of Thyroid Hormones in Hypothyroid and Hyperthyroid Patients

et al. 2005

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“…50 In line with these results, healthy, normal-weight adults the diurnal variation of TSH and leptin secretion are synchronous, suggesting a partial TSH regulation by leptin. 51 The direct relationships between 24-h TSH and adiposity indices as well as 24-h leptin are in agreement with other studies. 17,38,52 In our dataset, the latter relationship remained statistically significant after adjusting for sex, BMI, waist and FFM but was lost after adjusting for FM, 17,52 suggesting that mechanisms other than leptin modulate TSH concentrations in morbidly obese patients.…”

Section: Discussionsupporting

confidence: 91%

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

et al. 2008

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Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m 2 ) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m 2 ), sex-and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35±4 kg (or 26 ± 2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290 ± 31 vs 88 ± 4 pmol l À1 , P ¼ 0.0002), insulin resistant (23.5±2.8 vs 52.9±4.9 mmol min À1 kg FFM À1 , P ¼ 0.0006) and hyperleptinaemic (52.5±5.8 vs 10.9±3 ng ml À1 , P ¼ 0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02 ± 0.18 vs 1.09 ± 0.19 mU ml À1 of controls, P ¼ 0.01), whereas serum GH levels were suppressed (0.46±0.10 vs 3.01±1.15, P ¼ 0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4±2.7 ng ml À1 , P ¼ 0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.

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“…Humans with complete functional leptin deficiency due to defects in the leptin or leptin-receptor gene have altered TSH pulsatility (28) or central hypothyroidism (6). In small, uncontrolled studies, rmetHuLeptin increased free thyroxine and free T3 levels in leptindeficient children (4) and reversed the decrease in thyroid hormones in subjects during weight loss (18).…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans

Chan

Matarese

Shetty

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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192

158

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To elucidate whether the role of leptin in regulating neuroendocrine and immune function during short-term starvation in healthy humans is permissive, i.e., occurs only when circulating leptin levels are below a critical threshold level, we studied seven normal-weight women during a normoleptinemic-fed state and two states of relative hypoleptinemia induced by 72-h fasting during which we administered either placebo or recombinant methionyl human leptin (r-metHuLeptin) in replacement doses. Fasting for 72 h decreased leptin levels by Ϸ80% from a midphysiologic (14.7 ؎ 2.6 ng͞ml) to a low-physiologic (2.8 ؎ 0.3 ng͞ml) level. Administration of r-metHuLeptin during fasting fully restored leptin to physiologic levels (28.8 ؎ 2.0 ng͞ml) and reversed the fasting-associated decrease in overnight luteinizing hormone pulse frequency but had no effect on fasting-induced changes in thyroid-stimulating hormone pulsatility, thyroid and IGF-1 hormone levels, hypothalamic-pituitary-adrenal and renin-aldosterone activity. FSH and sex steroid levels were not altered. Shortterm reduction of leptin levels decreased the number of circulating cells of the adaptive immune response, but r-metHuLeptin did not have major effects on their number or in vitro function. Thus, changes of leptin levels within the physiologic range have no major physiologic effects in leptin-replete humans. Studies involving more severe and͞or chronic leptin deficiency are needed to precisely define the lower limit of normal leptin levels for each of leptin's physiologic targets.fasting ͉ reproductive D eficiency of the adipocyte-secreted hormone leptin (1) is associated with distinct abnormalities in energy-demanding processes such as neuroendocrine and immune function. Leptindeficient ob͞ob mice and humans with congenital complete leptin deficiency have abnormal neuroendocrine function, including hypogonadotropic hypogonadism, hypothalamic hypothyroidism, and͞or growth-hormone-axis abnormalities (2-6) and impaired cell-mediated immunity (4, 7), which are improved with leptin replacement (4,8). Similarly, starvation-induced decline of circulating leptin to very low levels in normal mice (9) and lean men (10) causes comparable neuroendocrine (9, 10) and immune defects (11, 12) that are significantly blunted or reversed with exogenous leptin.We have shown that an 80% decline of leptin levels from Ϸ2 to 0.3 ng͞ml in men mediates the fasting-induced suppression of gonadotropin and thyroid-stimulating hormone (TSH) pulsatility as well as sex steroid, insulin-like growth factor-1 (IGF-1), and thyroid hormone levels (10). Importantly, although observational studies have proposed that leptin regulates the hypothalamic-pituitarygonadal axis only when serum leptin levels fall below a ''threshold'' of Ϸ2 ng͞ml (13), the role of decreasing leptin levels to approximately, but not below, this threshold in leptin-replete humans with higher baseline leptin levels (e.g., normal-weight women) has not yet been directly studied.To elucidate whether such a threshold exists, below...

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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

Cited by 191 publications

References 61 publications

TSH Influences Serum Leptin Levels Independent of Thyroid Hormones in Hypothyroid and Hyperthyroid Patients

TSH Influences Serum Leptin Levels Independent of Thyroid Hormones in Hypothyroid and Hyperthyroid Patients

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans

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