Regulation of leptin by thyroid hormone in humans: Studies in vivo and in vitro

The influence of thyroid hormones on human adipose tissue leptin production and leptin gene expression was investigated in vitro and in vivo. Twelve w omen received 60 mu g triiodothyronine (T-3) per day for 7 days, which incr eased total T-3 by 195% (1.78 +/- 0.07 to 5.25 +/- 0.39 mU/L. P <.001), sig nificantly decreased thyrotropin ([TSH] 1.57 +/- 0.40 to 0.03 +/- 0.01 mU/L , P <.01), and increased energy expenditure (1,602 +/- 32 to 1.754 +/- 34 k ca1/24 h, P <.05). However, serum leptin did not change (9.36 +/- 1.6 v 8.9 0 +/- 1.3 mu g/L. nonsignificant). Human subcutaneous adipose tissue biopsi es from eight healthy women were incubated in vitro as small fragments with T-3 in concentrations from 1 to 50 nmol/L. Leptin production was inhibited dose-dependently. After 24 hours of incubation, a T-3 concentration of 50 nmol/L reduced basal leptin production by 42% (P <.05) and the stimulated l eptin production (dexamethasone 10 nmol/L) by 52% (P <.05). Leptin mRNA exp ression was measured by a semiquantitative multiplex reverse transcriptase- polymerase chain reaction (RT-PCR) method. Fifty nanomolars T-3 decreased b asal leptin mRNA expression by 47% compared with controls (P <.001), and th e stimulated leptin mRNA expression was reduced to a similar degree (53%). In conclusion, in human adipose tissue, T-3 (>20 nmol/L) inhibited leptin p roduction and leptin gene expression in vitro, whereas an elevation of T3 c orresponding to a moderate thyrotoxic state (T-3 5.25 +/- 0.39 nmol/L) was without any impact on serum leptin levels in vivo. Copyright (C) 1999 by W. B. Saunders Company.