title: 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.
abstract: Because alpha-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 (T(3) and T(4)), 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 T(4) 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.
authors.affiliation: Department of Neurobiology (C.F.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary 1083.
authors.forename: Csaba
authors.initials: C
authors.lastname: Fekete
authors.forename: Sumit
authors.initials: S
authors.lastname: Sarkar
authors.forename: William M
authors.initials: WM
authors.lastname: Rand
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: Charles H
authors.initials: CH
authors.lastname: Emerson
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
mesh_terms: D002001:Adipose Tissue, Brown / Q000033:anatomy & histology; D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004822:Epididymis; D006706:Homeostasis / Q000187:drug effects; D006728:Hormones / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; C046418:pro-thyrotropin releasing hormone; D011761:Pyrrolidonecarboxylic Acid