Supraphysiological triiodothyronine doses diminish leptin and adiponectin gene expression, but do not alter resistin expression in calorie restricted obese rats.

Thyroid hormones regulate energy balance and act on adipokines. However, while it is unclear what the effects are of calorie restriction and high doses of triiodothyronine (T(3)) on adipokines in obesity, thyroid hormones are illicitly administered in isolation or in association with a hypocaloric diet as an obesity treatment. The present study determined the effect of T(3) on serum concentrations and gene expression of the adipokines leptin, resistin, and adiponectin in calorie-restricted obese rats. Male Wistar rats received a hypercaloric diet for 20 weeks followed by calorie restriction for 8 weeks. The animals were then randomly divided into 3 groups: calorie restriction (OR), OR with 5 µg of T(3)/100 g BW (RS1), and OR with 25 µg of T(3)/100 g BW (RS2) for 2 weeks. Blood and adipose tissue samples were collected for biochemical, hormonal, and gene expression analyses. Serum concentrations of leptin (OR: 3.7±0.6, RS1: 3.8±1, RS2 0.2±0.07 ng/dl) and resistin (OR: 2.5±0.6, RS1: 2.5±0.5, RS2 1.6±0.3 ng/dl) were diminished at the higher dose, while serum adiponectin (OR: 31±7, RS1: 24±5, RS2 26±7 ng/dl) levels were lower in the low dose group. Administration of T(3) reduced leptin gene expression (OR: 0.91±0.1, RS1: 0.95±0.1, RS2 0.22±0.1) only at the higher dose, resistin expression (OR: 1.06±0.2, RS1: 1.04±0.1, RS2 0.88±0.2) was not influenced by T(3) treatment, and adiponectin expression (OR: 1.55±0.5, RS1: 0.95±0.15, RS2 0.97±0.13) was diminished independent of the T(3) dose. These results indicate that T(3), directly or indirectly, inhibits the expression of leptin and adiponectin in calorie restricted obese animals.

Tamoxifen inhibits transforming growth factor-alpha gene expression in human breast carcinoma samples treated with triiodothyronine.

OBJECTIVES: To examine the effects of triiodothyronine (T3), 17beta-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-alpha gene expression in primary breast cancer cell cultures and interactions between the different treatments. METHODS AND RESULTS: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3- mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-alpha mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-alpha mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-alpha mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. CONCLUSION: We demonstrate that TGF-alpha mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-alpha upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-alpha, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER alpha and beta; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2.