The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin.
Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, 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 plasma T4. ICV administration of a stable alpha-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, alpha-MSH increased thyrotropin releasing 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 suppression of the H-P-T axis.
Kim
M S
MS
Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom.
Small
C J
CJ
Stanley
S A
SA
Morgan
D G
DG
Seal
L J
LJ
Kong
W M
WM
Edwards
C M
CM
Abusnana
S
S
Sunter
D
D
Ghatei
M A
MA
Bloom
S R
SR
D054369:Agouti-Related Protein; D000818:Animals; D005215:Fasting; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D011506:Proteins / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044101:Receptors, Melanocortin; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood*; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D013972:Thyrotropin