Influence of thyroid status and growth hormone deficiency on ghrelin

To assess whether some of the alterations in energy homeostasis present in thyroid function disorders and GH deficiency could be mediated by ghrelin.

To assess the influence of thyroid status on ghrelin, adult male Sprague-Dawley rats were treated with vehicle (euthyroid), amino-triazole (hypothyroid) or l-thyroxine (hyperthyroid). The influence of GH on ghrelin was assessed in wild-type (control) and GH-deficient (dwarf) Lewis rats. Evaluation of gastric ghrelin mRNA expression in the stomach was carried out by Northern blot. Circulating levels of ghrelin were measured by radioimmunoassay.

Hypothyroidism resulted in an increase in gastric ghrelin mRNA levels (euthyroid: 100+/-3.2% vs hypothyroid: 127.3+/-6.5%; P<0.01), being decreased in hyperthyroid rats (70+/-5.4%; P<0.01). In keeping with these results, circulating plasma ghrelin levels were increased in hypothyroid (euthyroid: 124+/-11 pg/ml vs hypothyroid: 262+/-39 pg/ml; P<0.01) and decreased in hyperthyroid rats (75+/-6 pg/ml; P<0.01). Using an experimental model of GH deficiency, namely the dwarf rat, we found a decrease in gastric ghrelin mRNA levels (controls: 100+/-6% vs dwarf: 66+/-5.5%; P<0.01) and circulating plasma ghrelin levels (controls: 124+/-12 pg/ml vs dwarf: 81+/-7 pg/ml; P<0.01).

This study provides the first evidence that ghrelin gene expression is influenced by thyroid hormones and GH status and provides further evidence that ghrelin may play an important role in the alteration of energy homeostasis and body weight present in these pathophysiological states.