Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis.
Recent evidence suggests that neuropeptide Y (NPY), originating in neurons in the hypothalamic arcuate nucleus, is an important mediator of the effects of leptin on the central nervous system. As these NPY neurons innervate hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN) that produce the tripeptide, TRH, we raised the possibility that NPY may be responsible for resetting of the hypothalamic-pituitary-thyroid (HPT) axis during fasting. To test this hypothesis, the effects of intracerebroventricularly administered NPY on circulating thyroid hormone levels and proTRH messenger RNA in the PVN were studied by RIA and in situ hybridization histochemistry, respectively. NPY administration suppressed circulating levels of thyroid hormone (T(3) and T(4)) and resulted in an inappropriately normal or low TSH. These alterations were associated with a significant suppression of proTRH messenger RNA in the PVN, indicating that NPY infusion had resulted in a state of central hypothyroidism. Similar observations were made in NPY-infused animals pair fed to the vehicle-treated controls. These data are reminiscent of the effect of fasting on the thyroid axis and indicate that NPY may play a major role in the inhibition of HPT axis during fasting.
Fekete
C
C
Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.
Kelly
J
J
Mihály
E
E
Sarkar
S
S
Rand
W M
WM
Légrádi
G
G
Emerson
C H
CH
Lechan
R M
RM
D000273:Adipose Tissue / Q000187:drug effects; D002001:Adipose Tissue, Brown / Q000187:drug effects; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004822:Epididymis; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D017403:In Situ Hybridization; D020738:Leptin / Q000032:analysis; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology; D013972:Thyrotropin / Q000097:blood / Q000235:genetics; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D020738:Leptin; D009478:Neuropeptide Y; D011498:Protein Precursors; D012333:RNA, Messenger; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine