Neuropeptide Y (NPY) is one of the most important hypotha- lamic-derived neuropeptides mediating the effects of leptin on energy homeostasis. Central administration of NPY not only markedly stimulates food intake, but simultaneously in- hibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fast- ing. 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 polypeptide1–7, NPY19 –23, Ala31, Aib32 (aminoisobu- tyric acid), Q34]human pancreatic polypeptide) receptor ago- nists 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 hor- mones (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 paraventricu- lar 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 ob- served between the agonist-infused animals 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.

Neuropeptide Y1 and Y5 Receptors Mediate the Effects of Neuropeptide Y on the Hypothalamic- Pituitary-Thyroid Axis.

Csaba Fekete, Sumit Sarkar, William M. Rand, John W. Harney, Charles H. Emerson, Antonio C. Bianco, Annette Beck-sickinger, And Ronald M. Lechan. Endocrinology. December 2002. doi: 10.1210/en.2002-220574

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