The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

M. S. Kim; C. J. Small; S. A. Stanley; D. G.A. Morgan; L. J. Seal; W. M. Kong; C. M.B. Edwards; S. Abusnana; D. Sunter; M. A. Ghatei; S. R. Bloom

doi:10.1172/JCI8857

The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

M. S. Kim, C. J. Small, S. A. Stanley, D. G.A. Morgan, L. J. Seal, W. M. Kong, C. M.B. Edwards, S. Abusnana, D. Sunter, M. A. Ghatei, S. R. Bloom

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Abstract

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 α-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, α-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 α-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.

Original language	English
Pages (from-to)	1005-1011
Number of pages	7
Journal	Journal of Clinical Investigation
Volume	105
Issue number	7
DOIs	https://doi.org/10.1172/JCI8857
State	Published - Apr 2000
Externally published	Yes

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Kim, M. S., Small, C. J., Stanley, S. A., Morgan, D. G. A., Seal, L. J., Kong, W. M., Edwards, C. M. B., Abusnana, S., Sunter, D., Ghatei, M. A., & Bloom, S. R. (2000). The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. Journal of Clinical Investigation, 105(7), 1005-1011. https://doi.org/10.1172/JCI8857

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title = "The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin",

abstract = "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 α-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, α-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 α-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.",

author = "Kim, {M. S.} and Small, {C. J.} and Stanley, {S. A.} and Morgan, {D. G.A.} and Seal, {L. J.} and Kong, {W. M.} and Edwards, {C. M.B.} and S. Abusnana and D. Sunter and Ghatei, {M. A.} and Bloom, {S. R.}",

year = "2000",

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doi = "10.1172/JCI8857",

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AU - Kim, M. S.

AU - Small, C. J.

AU - Stanley, S. A.

AU - Morgan, D. G.A.

AU - Seal, L. J.

AU - Kong, W. M.

AU - Edwards, C. M.B.

AU - Abusnana, S.

AU - Sunter, D.

AU - Ghatei, M. A.

AU - Bloom, S. R.

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N2 - 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 α-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, α-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 α-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.

AB - 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 α-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, α-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 α-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.

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The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

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