Agouti-Related Protein (AGRP) has a central inhibitory action on the Hypothalamic-Pituitary-Thyroid (HPT) axis; Comparisons between the effect of AGRP and neuropeptide Y on energy homeostasis and the HPT axis

Csaba Fekete, Sumit Sarkar, William M. Rand, John W. Harney, Charles H. Emerson, Antonio C. Bianco, Ronald M. Lechan

Research output: Contribution to journalArticle

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Abstract

Because α-MSH has a potent stimulatory action on hypophysiotropic TRH synthesizing neurons in the hypothalamic paraventricular nucleus (PVN), preventing the effects of fasting on the gene expression of the TRH prohormone (proTRH), we hypothesized that agouti-related protein (AGRP), a melanocortin receptor antagonist, may exert a central inhibitory action on these neurons. To test the hypothesis, the effects of intracerebroventricularly administered AGRP on circulating thyroid hormone levels and proTRH mRNA in the hypothalamic paraventricular nucleus (PVN) were compared with the effects of the recently described central inhibitor of the HPT axis, neuropeptide Y (NPY). AGRP administration increased food consumption and weight gain, suppressed circulating levels of thyroid hormones (T3 and T4), and resulted in an inappropriately normal TSH. These alterations were associated with a significant suppression of proTRH mRNA in the PVN, indicating that AGRP infusion resulted in a state of central hypothyroidism. While similar observations were made in the NPY-infused animals, AGRP-treated animals had higher feeding efficiency, higher T4 levels, and lower type 2 iodothyronine deiodinase levels in brown adipose tissue than NPY-infused animals. These data demonstrate that AGRP and NPY have a similarly potent inhibitory action on the proTRH gene expression of hypophysiotropic neurons, indicating that both AGRP and NPY may play a major role in the inhibition of the HPT axis during fasting.

Original languageEnglish
Pages (from-to)3846-3853
Number of pages8
JournalEndocrinology
Volume143
Issue number10
DOIs
StatePublished - Oct 1 2002

Fingerprint

Agouti-Related Protein
Neuropeptide Y
Thyroid Gland
Homeostasis
Paraventricular Hypothalamic Nucleus
Neurons
Fasting
Melanocortin Receptors
Melanocyte-Stimulating Hormones
Gene Expression
Iodide Peroxidase
Messenger RNA
Brown Adipose Tissue
Triiodothyronine
Hypothyroidism
Thyroxine
Thyroid Hormones
Weight Gain
Efficiency
Food

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Agouti-Related Protein (AGRP) has a central inhibitory action on the Hypothalamic-Pituitary-Thyroid (HPT) axis; Comparisons between the effect of AGRP and neuropeptide Y on energy homeostasis and the HPT axis. / Fekete, Csaba; Sarkar, Sumit; Rand, William M.; Harney, John W.; Emerson, Charles H.; Bianco, Antonio C.; Lechan, Ronald M.

In: Endocrinology, Vol. 143, No. 10, 01.10.2002, p. 3846-3853.

Research output: Contribution to journalArticle

Fekete, Csaba ; Sarkar, Sumit ; Rand, William M. ; Harney, John W. ; Emerson, Charles H. ; Bianco, Antonio C. ; Lechan, Ronald M. / Agouti-Related Protein (AGRP) has a central inhibitory action on the Hypothalamic-Pituitary-Thyroid (HPT) axis; Comparisons between the effect of AGRP and neuropeptide Y on energy homeostasis and the HPT axis. In: Endocrinology. 2002 ; Vol. 143, No. 10. pp. 3846-3853.
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