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 hypophagia and leanness with an inappropriately high metabolic rate, suggesting a role for MCH in the control of energy balance. In order to further elucidate the mechanism by which MCH controls, energy expenditure, we have investigated the effects of MCH on the hypothalamic pituitary thyroid (HPT) axis. The thyroid axis is important in energy homeostasis and starvation leads to profound suppression of the HPT axis. MCH significantly reduces plasma TSH in vivo at 10 min (0.5 +/- 0.07 ng/ml, p < 0.05, n = 8) and 60 min (0.33 +/- 0.04 ng/ml, p < 0.01, n = 10) compared to saline (0.7 +/- 0.07 ng/ml and 0.69 +/- 0.07 ng/ml respectively) when administered intracerebroventricularly. Release of TRH form hypothalamic explants was significantly reduced in the presence of MCH 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 +/- 1.28 fmol/explant to 4.6 +/- 1.13 p < 0.05, n = 16), a peptide, also encoded in the pre-pro-MCH gene. MCH was also shown to significantly reduce TRH stimulated TSH release from dispersed pituitary cell cultures (basal = 0.5 +/- 0.06 ng/ml, 100 nM TRH = 0.9 +/- 0.2 ng/ml, p < 0.05 0.1 nM MCH = 0.5 +/- 0.1 ng/ml, p < 0.05, 1 nM MCH = 0.3 +/- 0.03 ng/ml, p < 0.01, 10 nM MCH = 0.4 +/- 0.02 ng/ml, p < 0.01, 1000 nM MCH = 0.4 +/- 0.05 ng/ml, P < 0.01, n = 4), although basal release of TSH from these cultures was unaffected. These data suggest a possible role for MCH in the control of energy homeostasis via inhibition of the thyroid axis.
Kennedy
A R
AR
Endocrine unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London, W12 ONN UK.
Todd
J F
JF
Stanley
S A
SA
Abbott
C R
CR
Small
C J
CJ
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D008543:Melanins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010907:Pituitary Hormones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D007028:Hypothalamic Hormones; D008543:Melanins; D009842:Oligopeptides; D010907:Pituitary Hormones; C522850:neuropeptide EI; D013973:Thyrotropin-Releasing Hormone; C019463:melanin-concentrating hormone; D013972:Thyrotropin