Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis.
Neuropeptide Y (NPY) is one of the most important hypothalamic-derived neuropeptides mediating the effects of leptin on energy homeostasis. Central administration of NPY not only markedly stimulates food intake, but simultaneously inhibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fasting. To identify the specific NPY receptor subtypes involved in the action of NPY on the HPT axis, we studied the effects of the highly selective Y1 ([Phe7,Pro34]pNPY) and Y5 ([chicken pancreatic polypeptide(1-7), NPY(19-23), Ala31, Aib32 (aminoisobutyric acid), Q34]human pancreatic polypeptide) receptor agonists on circulating thyroid hormone levels and proTRH mRNA in hypophysiotropic neurons of the hypothalamic paraventricular nucleus. The peptides were administered continuously by osmotic minipump into the cerebrospinal fluid (CSF) over 3 d in ad libitum-fed animals and animals pair-fed to artificial CSF (aCSF)-infused controls. Both Y1 and Y5 receptor agonists nearly doubled food intake compared with that of control animals receiving aCSF, similar to the effect observed for NPY. NPY, Y1, and Y5 receptor agonist administration suppressed circulating levels of thyroid hormones (T3 and T4) and resulted in inappropriately normal or low TSH levels. These alterations were also associated with significant suppression of proTRH mRNA in the paraventricular nucleus, particularly in the Y1 receptor agonist-infused group [aCSF, NPY, Y1, and Y5 (density units +/- SEM), 97.2 +/- 8.6, 39.6 +/- 8.4, 19.9 +/- 1.9, and 44.6 +/- 8.4]. No significant differences in thyroid hormone levels, TSH, or proTRH mRNA were observed between the agonist-infused FSanimals eating ad libitum and the agonist-infused animals pair-fed with vehicle-treated controls. These data confirm the importance of both Y1 and Y5 receptors in the NPY-mediated increase in food consumption and demonstrate that both Y1 and Y5 receptors can mediate the inhibitory effects of NPY on the HPT axis.
Fekete
Csaba
C
Department of Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
Sarkar
Sumit
S
Rand
William M
WM
Harney
John W
JW
Emerson
Charles H
CH
Bianco
Antonio C
AC
Beck-Sickinger
Annette
A
Lechan
Ronald M
RM
D000273:Adipose Tissue / Q000033:anatomy & histology; D002001:Adipose Tissue, Brown / Q000033:anatomy & histology / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000502:physiology*; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D011498:Protein Precursors; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D000071256:Uncoupling Protein 1; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine