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 women received 60 microg triiodothyronine (T3) per day for 7 days, which increased total T3 by 195% (1.78 +/- 0.07 to 5.25 +/- 0.39 mU/L, P < .001), significantly 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 kcal/24 h, P < .05). However, serum leptin did not change (9.36 +/- 1.6 v 8.90 +/- 1.3 microg/L, nonsignificant). Human subcutaneous adipose tissue biopsies from eight healthy women were incubated in vitro as small fragments with T3 in concentrations from 1 to 50 nmol/L. Leptin production was inhibited dose-dependently. After 24 hours of incubation, a T3 concentration of 50 nmol/L reduced basal leptin production by 42% (P < .05) and the stimulated leptin production (dexamethasone 10 nmol/L) by 52% (P < .05). Leptin mRNA expression was measured by a semiquantitative multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) method. Fifty nanomolars T3 decreased basal leptin mRNA expression by 47% compared with controls (P < .001), and the stimulated leptin mRNA expression was reduced to a similar degree (53%). In conclusion, in human adipose tissue, T3 (>20 nmol/L) inhibited leptin production and leptin gene expression in vitro, whereas an elevation of T3 corresponding to a moderate thyrotoxic state (T3 5.25 +/- 0.39 nmol/L) was without any impact on serum leptin levels in vivo.
Kristensen
K
K
Department of Endocrinology and Metabolism, Aarhus University Hospital, Denmark.
Pedersen
S B
SB
Langdahl
B L
BL
Richelsen
B
B
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000096:biosynthesis / Q000097:blood*; D008875:Middle Aged; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*
D005938:Glucocorticoids; D020738:Leptin; D014284:Triiodothyronine; D003907:Dexamethasone