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, Ronald M. Lechan

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 polypeptide1-7, NPY19-23, 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 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.

Original languageEnglish
Pages (from-to)4513-4519
Number of pages7
JournalEndocrinology
Volume143
Issue number12
DOIs
StatePublished - Dec 1 2002

Fingerprint

Neuropeptide Y
Thyroid Gland
Neuropeptide Y Receptors
Paraventricular Hypothalamic Nucleus
Eating
Thyroid Hormones
Messenger RNA
Cerebrospinal Fluid
Aminoisobutyric Acids
Triiodothyronine
Leptin
Neuropeptides
Thyroxine
neuropeptide Y5 receptor
Chickens
Fasting
Homeostasis
Neurons
Food
Peptides

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Fekete, C., Sarkar, S., Rand, W. M., Harney, J. W., Emerson, C. H., Bianco, A. C., ... Lechan, R. M. (2002). Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis. Endocrinology, 143(12), 4513-4519. https://doi.org/10.1210/en.2002-220574

Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis. / Fekete, Csaba; Sarkar, Sumit; Rand, William M.; Harney, John W.; Emerson, Charles H.; Bianco, Antonio C.; Beck-Sickinger, Annette; Lechan, Ronald M.

In: Endocrinology, Vol. 143, No. 12, 01.12.2002, p. 4513-4519.

Research output: Contribution to journalArticle

Fekete, C, Sarkar, S, Rand, WM, Harney, JW, Emerson, CH, Bianco, AC, Beck-Sickinger, A & Lechan, RM 2002, 'Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis', Endocrinology, vol. 143, no. 12, pp. 4513-4519. https://doi.org/10.1210/en.2002-220574
Fekete, Csaba ; Sarkar, Sumit ; Rand, William M. ; Harney, John W. ; Emerson, Charles H. ; Bianco, Antonio C. ; Beck-Sickinger, Annette ; Lechan, Ronald M. / Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis. In: Endocrinology. 2002 ; Vol. 143, No. 12. pp. 4513-4519.
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