Acute exogenous TSH administration stimulates leptin secretion in vivo

Abstract

TSH-receptor (TSHR) has been found in a variety of cell types, including preadipocytes and adipocytes. In vitro, TSH-mediated preadipocyte and adipocyte responses include proliferation, differentiation, survival, and lipolysis. Objective: To measure the response of serum leptin to exogenous administration of recombinant human TSH (rhTSH) in vivo. Patients: One hundred patients with differentiated thyroid cancer already treated by total thyroidectomy and 131 I remnant ablation were enrolled. Mean (GS.E.M.) body mass index (BMI) was 26.9G0.6 kg/m 2 . Methods: Patients received a standard dose of rhTSH for measurement of thyroglobulin in the follow-up of their disease. Blood samples were taken for the assay of TSH and leptin before the first administration of rhTSH (time 0), and 24 h (time 1), 48 h (time 2), 72 h (time 3), and 96 h (time 4) after the first administration of rhTSH. Results: Significant mean serum leptin increments, with respect to basal value, were 16, 13, 18, and 11% at times 1, 2, 3, and 4 respectively. Significant positive correlations of leptin-area under the curve with respect to basal leptin levels (rZ0.43; P!0.0001) and BMI (rZ0.32; P!0.005) were observed. Conclusions: Acute rhTSH administration in hypothyroid subjects under L-thyroxine therapy produces a rise in serum leptin. This increase is proportional to the adipose mass suggesting that a functioning TSHR is expressed on the surface of adipocytes. The role that TSHR activation in adipocytes might play in physiological and pathological conditions remains a matter of investigation.

Association between serum TSH concentration within the normal range and adiposity

“…Another hypothesis is that the association between serum TSH and body weight may be due to leptin (38). In agreement with the leptin hypothesis, a recent study in treated thyroid cancer patient found an increase in serum leptin after acute recombinant human TSH administration, which was proportional to adipose mass (39). Also, the highest correlations in the association between BMI and serum TSH concentration (rZ0.91) was shown among morbidly obese participants (12).…”

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

“…A bidirectional interaction is suggested by the intriguing observation that TSH receptors are expressed on adipocytes (52) and that the in vivo administration of recombinant human TSH at supra-physiological doses can induce the release of small but significant amounts of leptin which are proportional to the adipose mass (53). The latter finding confirms that functioning TSH receptors are expressed on the surface of white adipocytes.…”

Obesity and thyroid cancer

“…Potential stimulators of TSH production, explaining the increase in TSH in obese patients, include hormonal mediators of adipose tissue, especially leptin (Rosenbaum et al 2000, Sari et al 2003. Apart from modulating food intake and energy expenditure, leptin acts as a neuroendocrine regulator of the hypothalamic-pituitary-thyroid axis by regulating the expression of TRH in the paraventricular nucleus; leptin secretion by adipose tissue will then be stimulated by TSH (Menendez et al 2003, Oge et al 2005, Feldt-Rasmussen 2007, Santini et al 2010. Leptin may also affect deiodinases, activating the T 4 to T 3 conversion (Zimmermann-Belsing et al 2003, Reinehr 2010.…”