Thyroid hormones modulate the endocrine and autocrine/paracrine actions of leptin on thyrotropin secretion

Abstract

We investigated the influence of hypo-and hyperthyroidism on the ability of leptin to modulate TSH secretion. Two hours after receiving leptin (8 µg leptin/100 g BW; s.c.), hyperthyroid rats (10 µg thyroxine (T4)/100 g body weight (BW) for 5 days) showed a 1·7-fold increase in serum TSH (P<0·05); in hypothyroid rats, leptin had no effect. Hemi-pituitaries of hyperthyroid rats incubated with 10 9 and 10 7 M leptin showed reductions in TSH release of 40 and 50% respectively (P<0·05); incubation with 1:2000 and 1:500 dilutions of antiserum against leptin resulted in 3-and 4-fold higher TSH release (P<0·05 and P<0·001 respectively). However, in hypothyroid pituitaries leptin or the antiserum had no effect. The results suggest that the in vivo and in vitro responsiveness of TSH to leptin is abolished in hypothyroidism and is preserved in short-term hyperthyroidism, in comparison to previous reports in euthyroidism. In addition, the inhibitory action of pituitary leptin is enhanced in hyperthyroid glands, which may suggest a role for locally produced leptin in the suppression of TSH release associated with hyperthyroidism.

Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

“…However, there was a small decrease in the STAT3 content in hyperthyroid pituitaries, and pSTAT3 and the ObRb receptors were unaltered; therefore, they may be able to respond normally to leptin. These results are consistent with our previous study in which, employing the same protocol of short-term hyperthyroidism in rats, we observed that hyperthyroid rats or the isolated pituitary glands from hyperthyroid rats exhibited the same response as those in the euthyroid condition (Da Veiga et al 2004). …”

“…Our finding that hypothyroidism was associated with the down-regulation of proteins of the leptin signalling pathway in the hypothalamus, namely reducing the content of ObRb and pSTAT3, suggests that the action of leptin might be reduced at the hypothalamic level in hypothyroidism. This result is consistent with our previous study (Da Veiga et al 2004), showing that in hypothyroid rats, leptin lost its ability to increase serum TSH, because, as demonstrated by others, the STAT3 pathway is the primary intracellular mediator of the direct and indirect effects of leptin to stimulate TRH expression in PVN neurons (Legradi et al 1997, Friedman & Halaas 1998, Ahima & Flier 2000, Guo et al 2004, Huo et al 2004. However, it remains to be demonstrated whether C CALVINO and others .…”

“…Previous studies have indicated that STAT3 activation through tyrosine phosphorylation plays an important role in leptin signal transduction at the pituitary gland (Tsumanuma et al 2000, Lloyd et al 2001. Although pituitary cells other than thyrotropes also express leptin receptors (Sone et al 2001), our findings suggest that reduced leptin signalling in the whole pituitary gland might contribute to the abolishment of the direct effect of leptin on TSH secretion from the isolated pituitaries of the hypothyroid rats that were previously studied (Da Veiga et al 2004). The mechanisms of leptin resistance are not completely understood, but it has been shown that high SOCS3 in the hypothalamus of hyperleptinaemic rats might exert a central role in the leptin resistance of obesity models (Bjørbaek et al 1999, Mori et al 2004).…”

“…These in vivo and in vitro pituitary effects of leptin upon TSH secretion observed in euthyroid rats were preserved in hyperthyroid rats but not in hypothyroid rats (Da Veiga et al 2004), suggesting that hypothyroidism abolished the action of leptin at the HPT axis. Therefore, we raised the question of whether alterations in leptin signalling through the STAT3 pathway in the hypothalamus and pituitary might justify the lack of TSH response to leptin in hypothyroidism.…”

Prenatal undernutrition and postnatal overnutrition alter thyroid hormone axis function in sheep

“…upon binding to specific receptors in the arcuate nucleus of the hypothalamus, induce neuroendocrine changes resulting in increased release of TRH from the hypothalamus, TSH from the pituitary gland, and thereby TH from the thyroid glands (Costa da Veiga et al 2004). …”