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Effects of Melanocortin Receptor Ligands on Thyrotropin‐Releasing Hormone Release: Evidence for the Differential Roles of Melanocortin 3 and 4 Receptors
Author(s) -
Kim M. S.,
Small C. J.,
Russell S. H.,
Morgan D. G. A.,
Abbott C. R.,
AlAhmed S. H.,
Hay D. L.,
Ghatei M. A.,
Smith D. M.,
Bloom S. R.
Publication year - 2002
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2002.00769.x
Subject(s) - medicine , endocrinology , melanocortin , agonist , thyrotropin releasing hormone , receptor , chemistry , melanocyte stimulating hormone , melanocortin receptor , antagonist , hormone , melanocortin 4 receptor , biology
The hypothalamic melanocortin system is important in the central regulation of food intake and body weight. We have previously demonstrated that intracerebroventricular administration of α‐melanocyte stimulating hormone (α‐MSH), a nonselective MC3 and MC4 receptor agonist, stimulated plasma thyroid‐stimulating hormone, and agouti‐related protein (AgRP), an MC3 and MC4 receptor antagonist, suppressed it. In this study, we investigated the effects of MC3 and MC4 receptor (MC3‐R and MC4‐R) selective agonists and antagonists on the release of thyrotropin‐releasing hormone (TRH) from hypothalamic explants in vitro . α‐MSH stimulated TRH release from the rat hypothalamic explants (α‐MSH 100 n M 230 ± 22.9% basal, P < 0.005). In contrast, γ 2 ‐MSH, a selective MC3‐R agonist, suppressed TRH release (γ 2 ‐MSH 10 µ M 76.2 ± 7.4% basal, P < 0.05). AgRP (83‐132), a nonselective MC3/4‐R antagonist, induced no change in TRH release whilst JKC‐363 (cyclic [Mpr 11 , D‐Nal 14 , Cys 18 , Asp 22 ‐NH 2 ]‐β‐MSH 11‐22), a selective MC4‐R antagonist, suppressed it (JKC‐363 10 n M 57.2 ± 11.5% basal, P < 0.05). Both AgRP (83‐132) and JKC‐363 blocked α‐MSH stimulated TRH release but only AgRP (83‐132) blocked the inhibitory effect of γ 2 ‐MSH on TRH release. These data suggest differential roles for the MC3 and MC4 receptors in TRH release; MC3‐R agonism inhibiting and MC4‐R agonism stimulating TRH release.