Ghrelin affects the hypothalamus–pituitary–thyroid axis in humans by increasing free thyroxine and decreasing TSH in plasma

Abstract

Objective: Ghrelin promotes a positive energy balance, e.g. by increasing food intake. Stimulation of the activity of the hypothalamus-pituitary-thyroid (HPT) axis promotes a negative energy balance, e.g. by increasing energy expenditure. We therefore hypothesized that ghrelin suppresses the HPT axis in humans, counteracting its energy-saving effect. Design and methods: In this single-blind, randomized, cross-over study, we determined secretion patterns of free triiodothyronine (fT 3 ), free thyroxine (fT 4 ), TSH, and thyroid-binding globulin (TBG) between 2000 and 0700 h in 20 healthy adults (10 males and 10 females, 25.3G2.7 years) receiving 50 mg ghrelin or placebo at 2200, 2300, 0000, and 0100 h. Results: FT 4 plasma levels were significantly higher after ghrelin administration than after placebo administration from 0000 h until 0620 h except for the time points at 0100, 0520, and 0600 h. TSH plasma levels were significantly lower from 0200 until the end of the study at 0700 h except for the time points at 0540, 0600, and 0620 h. The relative increase of fT 4 (area under the curve (AUC) 0130-0700 h (ng/dl!min): placebo: 1.31G0.03; ghrelin: 1.39G0.03; PZ0.001) was much weaker than the relative decrease of TSH (AUC 0130-0700 h (mIU/ml!min): placebo: 1.74G0.12; ghrelin: 1.32G0.12; PZ0.007). FT 3 and TBG were not affected. Conclusions: This is the first study to report that ghrelin affects the HPT axis in humans. The early fT 4 increase was possibly induced by direct ghrelin action on the thyroid where ghrelin receptors have been identified. The TSH decrease might have been caused by ghrelin-mediated inhibition at hypothalamic level by feedback inhibition through fT 4 , or both.

Ghrelin in mental health, sleep, memory

“…The trijodothyronine (fT 3 ) and thyroid-binding globulin (TBG) were not affected (Kluge et al, 2010b). These findings support the hypothesis that ghrelin suppresses the HPT axis in humans, which counteracts its energy-saving effects.…”

Paracrine Regulation of Thyroid-Hormone Synthesis by C Cells

“…These results has been supported by a study from our research group which have demonstrated that, effectively, ghrelin has a direct effect on the three tissue-specific genes involved in thyroid hormone synthesis: thryroperoxidase (TPO), Na + /I -symporter (NIS) and thyroglobulin [144,145]. This direct effect on follicular-cell activity could be responsible for the effects observed at the hypothalamus-pituitary-thyroid axis [144,145].…”

“…In regard to the implication of ghrelin in thyroid hormone synthesis, after the demonstration of the ghrelin receptor in human thyroid tissue [143], Kluge et al [144] described a ghrelinmediated decrease in TSH levels and an increase of serum T4, probably due to a ghrelin direct stimulatory action on the thyroid gland. These results has been supported by a study from our research group which have demonstrated that, effectively, ghrelin has a direct effect on the three tissue-specific genes involved in thyroid hormone synthesis: thryroperoxidase (TPO), Na + /I -symporter (NIS) and thyroglobulin [144,145].…”

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

“…Specifically, AG administration was shown to inhibit LH release in rats (Furuta et al 2001, Fernandez-Fernandez et al 2005, and FSH and LH in healthy men (Kluge et al 2007, Lanfranco et al 2008, Kluge et al 2009) and women (Messini et al 2010a, Kluge et al 2012. On the other hand, the role of AG on TSH release is not well defined as some studies indicate a lack of direct effect on TSH release in humans (Takaya et al 2000, Hataya et al 2001, Nagaya et al 2001, while a recent study indicates that AG administration could induce a decrease in TSH release in healthy subjects (Kluge et al 2010). Given that this study showed that AG was able to increase thyroxine, the authors speculate that the effect of AG on TSH might be mediated by a indirect action at the hypothalamic level through a thyroxine-dependent feedback (Kluge et al 2010).…”

“…On the other hand, the role of AG on TSH release is not well defined as some studies indicate a lack of direct effect on TSH release in humans (Takaya et al 2000, Hataya et al 2001, Nagaya et al 2001, while a recent study indicates that AG administration could induce a decrease in TSH release in healthy subjects (Kluge et al 2010). Given that this study showed that AG was able to increase thyroxine, the authors speculate that the effect of AG on TSH might be mediated by a indirect action at the hypothalamic level through a thyroxine-dependent feedback (Kluge et al 2010). Finally, glycoprotein hormones a chain (CGA) is the common subunit for FSH, LH, and TSH (and chorionic gonadotropin hormones) and is normally released as part of a heterodimer with these b subunits.…”