Melanin-concentrating hormone (MCH) suppresses thyroid stimulating hormone(TSH) release, in vivo and in vitro, via the hypothalamus and the pituitary

Melanin-concentrating hormone (MCH) is an orexigenic peptide encoded in the pre-pro MCH gene. Targeted deletion of MCH causes a phenotype of hypophagi a and leanness with an inappropriately high metabolic rate, suggesting a ro le for MCH in the control of energy balance. In order to further elucidate the mechanism by which MCH controls energy expenditure, we have investigate d the effects of MCH on the hypothalamic pituitary thyroid (HPT) axis. The thyroid axis is important in energy homeostasis and starvation leads to pro found suppression of the HPT axis. MCH significantly reduces plasma TSH in vivo at 10 min (0.5 +/-0.07ng/ml, p <0.05, n=8) and 60 min (0.33 +/-0.04ng/ ml, p <0.01, n=10) compared to saline (0.7 +/-0.07ng/ml and 0.69 +/-0.07ng/ ml respectively) when administered intracerebroventricularly. Release of TR H from hypothalamic explants was significantly reduced in the presence of M CH production (7.1 +/-0.99 fmol/explant to 2.3 +/-0.4 fmol/explant p <0.01, n=18) and Neuropeptide EI (NEI) (8.47 +/-1.28fmol/explant to 4.6 +/-1.13 p <0.05, n=16), a peptide, also encoded in the pre-pro-MCH gene. MCH was als o shown to significantly reduce TRH stimulated TSH release from dispersed p ituitary cell cultures (basal=0.5 +/-0.06 ng/ml, 100nM TRH=0.9 +/-0.2 ng/ml , p <0.05 0.1nM MCH=0.5 +/-0.1 ng/ml, p <0.05, 1nM MCH=0.3 +/-0.03 ng/ml, p <0.01, 10nM MCH=0.4 +/-0.02 ng/ml, p <0.01, 1000nM MCH=0.4 +/-0.05 ng/ml, P <0.01, n=4), although basal release of TSH from these cultures was unaffe cted. These data suggest a possible role for MCH in the control of energy h omeostasis via inhibition of the thyroid axis.