Ms. Kim et al., The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin, J CLIN INV, 105(7), 2000, pp. 1005-1011
Prolonged fasting is associated with a downregulation of the hypothalamo-pi
tuitary thyroid (H-P-T) axis, which is reversed by administration of leptin
. The hypothalamic melanocortin system regulates energy balance and mediate
s a number of central effects of leptin. In this study, we show that hypoth
alamic melanocortins can stimulate the thyroid axis and that their antagoni
st, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular
(ICV) administration of Agrp (83-132) decreased plasma thyroid stimulating
hormone (TSH) in fed male rats. Intraparaventricular nuclear administration
of Agrp (83-132) produced a long-lasting suppression of plasma TSH, and pl
asma T4. ICV administration of a stable alpha-MSH analogue increased plasma
TSH in 24-hour-fasted rats. In vitro, alpha-MSH increased thyrotropin rele
asing hormone (TRH) release from hypothalamic explants. Agrp (83-132) alone
caused no change in TRH release but antagonized the effect of alpha-MSH on
TRH release. Leptin increased TRH release from hypothalami harvested from
48-hour-fasted rats. Agrp (83-132) blocked this effect. These data suggest
a role for the hypothalamic melanocortin system in the fasting-induced supp
ression of the H-P-T axis.