Functional Neuroanatomy of Hypothalamic Neurons

Co-Localization of Growth Hormone Secretagogue Receptor and NPY mRNA in the Arcuate Nucleus of the Rat
Mette Georgi Willesen, Peter Kristensen, John Rømer

Department of Histology, Health Care Pharmacology, Health Care Discovery, Novo Nordisk A/S, Bagsværd, Denmark

Address of Corresponding Author

Neuroendocrinology 1999;70:306-316 (DOI: 10.1159/000054491)

  Key Words

• Growth hormone secretagogue receptor
• Co-localization
• Dual in situ hybridization
• Neuropeptide Y
• Pro-opiomelanocortin
• Somatostatin
• Arcuate nucleus
• Rat

  Abstract

Growth hormone secretagogues (GHS) are small, synthetic compounds which have the potential of releasing growth hormone (GH) from the pituitary. The mechanism of action of GHS has not been fully elucidated. A specific GHS receptor (GHS-R) is expressed in the pituitary gland and in several areas of the brain including the hypothalamus. We have characterized the GHS-R-mRNA-expressing neurons with respect to co-expression of selected neurotransmitters in the hypothalamus. This was done by dual chromogenic and autoradiographic in situ hybridization with riboprobes for GHS-R mRNA and neuropeptide Y (NPY), pro-opiomelanocortin (POMC), somatostatin (SRIH) or GH-releasing hormone (GHRH) mRNA. In the arcuate nucleus, GHS-R mRNA was expressed in 94 ± 1% of the neurons expressing NPY, 8 ± 2% of those expressing POMC and 30 ± 6% expressing SRIH mRNA. 20-25% of the GHRH- mRNA-expressing neurons contained GHS-R mRNA, whereas the vast majority of the arcuate GHS-R-mRNA-containing cells did not contain GHRH mRNA. The finding of a significant co-expression of GHS-R and NPY mRNA in the arcuate nucleus is in accordance with the previous demonstration by Dickson et al. that c-Fos is induced in NPY neurons following GHS administration. These results indicate that GHS have other effects on neuroendocrine regulation than GH release via GHRH neurons. Stimulation of the arcuate NPY neurons via GHS-R may explain the increased appetite and the cortisol release seen after administration of some GHS compounds.

Copyright © 1999 S. Karger AG, Basel

  Author Contacts

John Rømer
Histology, Health Care Pharmacology
Novo Nordisk A/S, Novo Alle 1, 6A1.20
DK-2880 Bagsværd (Denmark)
Tel. +45 4442 3018, Fax +45 4442 6220

  Article Information

Received: Received: April 28, 1999
Accepted after revision: July 12, 1999
Number of Print Pages : 11
Number of Figures : 4, Number of Tables : 1, Number of References : 40